PharmaFocus Asia, Issue 20

Issue 20 2014

www.pharmafocusasia.com

Rethinking the future New business models for pharma

Non-Clinical Drug Development in Asia

Pharma Outsourcing

A literature review and landscape assessment

Facing significant challenges

Processing equipment and packaging machinery from Bosch achieve the agreed performance. Day after day. Year after year. GMP-compliant systems ensure the required pharmaceutical product quality. Simple validation, cleaning and sterilization processes and low maintenance requirements increase production efficiency. Experienced employees with extensive know-how guarantee professional service worldwide. Learn more at www.boschpackaging.com

schwarzspringer

Processed and packaged as promised. Bosch.

Foreword

New Pharma Business Models Regaining power Changing patterns of diseases, ageing

industry will have to spend exclusively to protect

population, price controls, dry R&D pipelines,

patents and for better patenting patterns.

patent expirations for many blockbuster drugs

In addition to this, collaborations, alliances

and declining global generic market opportunities

with smaller biotechnology companies and better

are a wake-up call for pharma. Moreover, the

biotechnology and pharmaceutical outsourcing

shift in focus to improved outcomes is pushing

options will develop effective new medicines

pharma companies to rethink on the existing

more economically.

business models for more productive R&D solutions at low costs.

The cover story in this issue by Patrick Flochel, EY Global Pharmaceutical Sector Leader

To achieve this, pharma companies need to

traces how pricing and regulatory challenges

move from a traditional pharmaceutical company

are changing the business model from Pharma

to becoming a fully integrated pharmaceutical

1.0 to Pharma 2.0. The article also highlights

network. A fully integrated network focuses on

how this transformation is impacting pharma

different therapeutic areas covering R&D to sales

companies’ operations. Changing incentives

and marketing, different enabling technologies,

are reshaping the healthcare ecosystem and

such as genomics, proteomics and stem cell

Pharma 3.0’s new focus on healthcare outcome

research; and management of outcomes.

is opening doors for non-traditional players.

Increased spending on R&D will help

Employing these strategies and proactively

companies to refresh their pipelines. According

tackling challenges will become decisive for

to Battelle and R&D Magazine, R&D spending

the future of pharma industry in its attempt to

in the global life science industry is expected

regain the power and meet the promises.

to rise more than 3 per cent to US$201 billion in 2014. The biopharmaceuticals industry will account for about 85 per cent of that total, with top US spenders including Pfizer, Merck, and Johnson & Johnson, as well as European giants Novartis and Roche.

New formulations with shorter patent lives are due to expire very soon causing scarcity in block-buster drugs for patients. Hence, the

Prasanthi Potluri Editor

www.pharmafocusasia.com

3

Content COVER STORY 14 Rethinking The Future New business models for pharma Patrick Flochel, EY Global Pharmaceutical Sector Leader Switzerland

STRATEGY 5

Non-Clinical Drug Development in Asia A literature review and landscape assessment

Stella Stergiopoulos, Project Manager, Tufts Center for the Study of Drug Development, US

12 Pharma Outsourcing Facing significant challenges Adam Dion, Analyst, Industry Dynamics, GlobalData, US

RESEARCH & DEVELOPMENT 20 Developing New Vaccines Novel approach and standardised methodologies

David Klatzmann, Professor, Laboratory of Biology and Therapeutic of Immune Diseases, University Pierre and Marie Curie, France

CLINICAL TRIAL 24 Issues & Concerns in Conducting Clinical Trials in India

Milind Antani, Head, Pharma & Life Science Practice Group Nishith Desai Associates, India

4

Gowree Gokhale, Partner, Nishith Desai Associates, India

P h a rm a F o c u s A s i a

ISSUE - 20 2014

information technology 28 IT Clouds In Life Sciences

Key to long term sustainability Alan S Louie, Research Director, IDC Health Insights, USA

39 Industry Reports 49 Books

PIONEERING PARTNER FOR PEPTIDES Building on our heritage, we pioneer innovations to deliver the best quality for every peptide need.

• More than 40 Years Experience in Peptide Chemistry • Over 0 Generic APIs • Process Development & Custom Manufacturing • Comprehensive Technical and Regulatory Support • Multi-Kg Scale cGMP Manufacturing Facilities in USA and Europe www.bachem.com 5

P h a rm a F o c u s A s i a

ISSUE - 20 2014

Advisory Board

Editor Prasanthi Potluri Alan S Louie Research Director, Health Industry Insights an IDC Company, USA

Art Director M A Hannan

Christopher-Paul Milne Associate Director, Tufts Center for the Study of Drug Development, Tufts University, USA

Product Managers Breiti Roger Khaja Ameeruddin Jeff Kenney

Douglas Meyer Senior Director, Aptuit Informatics Inc., USA

Frank A Jaeger Director, New Business Development Solvay Pharmaceuticals, Inc., USA

Georg C Terstappen Chief Scientific Officer, Siena Biotech S.p.A., Italy

Senior Product Associates Vineetha Gadhe Vinay Kumar Makthala Veronica Wilson Ben Johnson Compliance Team P Bhavani Prasad P Shashikanth Sam Smith Steven Banks CRM Naveen M Subscriptions incharge Vijay Kumar Gaddam

Kenneth I Kaitin Director and Professor of Medicine, Tufts Center for the Study of Drug Development, Tufts University, USA

Laurence Flint Associate Director, Clinical Research Schering-Plough Research Institute, USA

Neil J Campbell CEO, Mosaigen Inc. and Partner Endeavour Capital Asia Ltd., USA

IT Team Ranganayakulu V T Krishna Deepak Yadav Head-Operations S V Nageswara Rao

Pharma Focus Asia is published by

In Association with

A member of

Phil Kaminsky Founder, Center for Biopharmaceutical Operations University of California, Berkeley, USA

Rustom Mody Director, Quality and Strategic Research Intas Biopharmaceuticals Limited, India

Confederation of Indian Industry

Ochre Media Private Limited Media Resource Centre,#9-1-129/1,201, 2nd Floor, Oxford Plaza, S.D Road, Secunderabad - 500003, Andhra Pradesh, INDIA, Phone: +91 40 4961 4567, Fax: +91 40 4961 4555 Email: info@ochre-media.com www.pharmafocusasia.com|www.verticaltalk.com|www.ochre-media.com

Sanjoy Ray Director, Technology Innovation Merck Research Laboratories, USA Sasikant Misra Management Consultant and Ex-Deputy Director CII, Drugs and Pharma Sector 6

P h a rm a F o c u s A s i a

ISSUE - 20 2014

Š Ochre Media Private Limited. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, photocopying or otherwise, without prior permission of the publisher and copyright owner. Whilst every effort has been made to ensure the accuracy of the information in this publication, the publisher accepts no responsibility for errors or omissions.

The products and services advertised are not endorsed by or connected with the publisher or its associates. The editorial opinions expressed in this publication are those of individual authors and not necessarily those of the publisher or of its associates.

Copies of Pharma Focus Asia can be purchased at the indicated cover prices. For bulk order reprints minimum order required is 500 copies, POA.

strategy

Non-Clinical Drug Development in Asia

A literature review and landscape assessment Contract Research Organisations (CROs) across service areas are proliferating globally, yet most data on the CRO market focuses primarily on US and European clinical research activities. The Tufts Center for the Study of Drug Development (Tufts CSDD) has completed an initial study looking at key geographic CRO hubs that encompass a diverse set of global and local contract service companies that provide a range of non-clinical, analytical, clinical and commercial services. Tufts CSDD also conducted a literature review of the CRO landscape in Asia, in addition to estimating the CRO markets by functional area and expertise. The results of this study and their implications will be discussed.

Stella Stergiopoulos, Project Manager, Tufts Center for the Study of Drug Development, US

N

on-clinical development costs (activities including drug discovery; biology research; chemistry research; pre-clinical) continues to account for a large percentage of overall drug Research and Development (R&D) costs.

The Pharmaceutical Research and Manufacturers of America (PhRMA) estimated that in 2012 US$11.9 billion, or 23.8 per cent, of overall R&D costs are attributed to prehuman/preclinical1, up from US$10.5 billion in 2011 (~22 per cent). Only phase three continues to be more costly than nonclinical R&D. In 2013, Tufts CSDD estimated that the mean cost of non-clinical drug development to be US$6.1 million per compound, with Chemistry, Manufacture and Control (CMC) costs 1 Pharmaceutical Research and Manufacturers of America: 2014 Biopharmaceutical Research Industry Profile. http:// www.phrma.org/sites/default/files/pdf/2014_PhRMA_ PROFILE.pdf.

Accessed May 9, 2014.

www.pharmafocusasia.com

7

strategy

India

50%

China

18%

Japan

12%

Taiwan

6%

South Korea

4%

Pakistan

2%

Malaysia

2%

Singapore

1%

Hong Kong

1%

Bangladesh

1%

Indonesia

0.5%

Thailand

0.5%

Philippines

0.5%

Vietnam

0.5%

Source: Tufts CSDD, 2014 using S&P Capital IQ (select Capital IQ classifications). Tufts CSDD Figure1: May 2014 percentage breakdown of operating CROs in Asia Pacific (by county)

accounting for roughly 50 per cent of that average2.

Strategies behind non-clinical R&D have continued to mature in an effort improve operation and infrastructure efficiency. One main strategy involves increasing the use of outsourcing across the value chain. In the 2013 study, Tufts CSDD interviewed representatives from nine mid- to large-sized pharmaceutical organisations, inquiring specifically about current non-clinical outsourcing practices. The majority of respondents noted that routine activities, such as CMC, toxicology, pharmacokinetic and metabolic studies are outsourced either occasionally or regularly, while more strategic activities, such as IND document preparation, mainly remain in-house3. Data on Contract Research Organisations (CROs) support this finding, as the number of CROs has increased four-fold, from 800 companies in the US in 2000 to more than 3,200 companies in 20114. In 2011, 26 per 2 Stergiopoulos S Getz KA. Characterizing the Cost of Non-Clinical Development Activity: Understanding a critical R&D segment. Contract Pharma, June 2013. http://www.contractpharma.com/issues/2013-06/view_features/characterizing-the-cost-of-non-clinical-developmentactivity/. Accessed May 9, 2014.

3 Ibid.

4 Ibid.

8

P h a rm a F o c u s A s i a

ISSUE - 20 2014

The majority of operating CROs are in the most mature countries: 50 per cent have their headquarters in India, and 18 per cent in China. Japan and Taiwan account for 12 per cent and 6 per cent of total number of companies respectively. cent of the 3,200 companies offered non-clinical services, accounting for roughly 21 per cent of the overall US contract R&D market (between US$6.8 and US$8.1 billion)5.

In 2013, Tufts CSDD conducted a study to size the global market for contract R&D market services as a whole and note that despite the dramatic 5 Getz KA et al. Resizing the Global Contract R&D Services Market: A new study revises estimates of the market.

Contract Pharma, June 2012. http://www.contractpharma.com/issues/2012-06/view_features/resizing-the-globalcontract-rd-services-market/. Accessed May 9, 2014.

increase in non-clinical outsourcing activity, limited information on the size of the non-clinical outsourcing market in Asia has been published6.

Data characterising specific functions within drug development has focused predominantly on individual service areas or specific countries. As a follow-up to the 2013 study, this study and literature review look to specifically characterise the Asian non-clinical outsourcing market. The first section focuses on the economics of outsourcing in Asia, while the second section focuses on specific country offerings.

The economics of outsourcing in Asia

At the global level, non-clinical research activities account for 14 per cent of the total contract services market, or between US$11 and US$15 billion, with 9 per cent of that 14 per cent (between US$990 million and US$1.4 billion dollars) coming from companies in Asia Pacific7.

In 2012, Steven Aldrich of Kalorama Information estimated that the 2011 drug discovery outsourcing marketin Brazil, Russia, India and China (BRIC) was US$9.4 billion. He also estimated that the drug discovery outsourcing market in BRIC grew 15 per cent from 2010 to 20118. Aldrich attributes the rise in the number of organisations offering discovery services as ‘BRIC nations are seeing the largest growth since they have been developing the academic and scientific workforce necessary to carry out high-tech core functions.’9 Figure 1 contains a percentage breakdown of operating contract research 6 Lamberti, MJ et al. Characterizing the global market for Contract R&D Services. Chimica Oggi – Chemistry Today.

CROsCMOs Vol 3(4) July/August 2013. http://www. teknoscienze.com/Articles/Chimica-Oggi-Chemistry-TodayCharacterizing-the-global-market-for-Contract-R-amp-DServices.aspx#.UoucnJEmX4R Last accessed May 9, 2014.

7 Ibid.

8 Aldrich S. Discovery Outsourcing Report: BRIC drug discovery companies lead the market to $11 billion.

Contract Pharma. Sept 2012. http://www.contractpharma. com/issues/2012-09/view_features/discovery-outsourcingreport/. Last accessed May 9, 2014.

9 Ibid.

100 %

KSP plus

clamping force block

control

© 2014 SCHUNK GmbH & Co. KG

300

NSR Robot Coupling kg load bearing capacity

NSA

100

Automated Palletizing System

kN Holding Force

Your automated machine loading.

It’s time to make use of your machine’s full potential. www.in.schunk.com/machine-potential Jens Lehmann, Brand Ambassador of SCHUNK, the family-owned company

9

P h a rm a F o c u s A s i a

ISSUE - 20 2014

strategy

Reproduction Toxicity (RAT) China

India

Japan

Korea

USA

USD Thousands

$178 $121

$115 $27

$53

Subchronic Toxicity (Rat, 13 weeks) China

India

Japan

Korea

Singapore

USA

USD Thousands

$322 $239

$245 $180

$50

$66

Chronic Toxicity (Monkey, 9 Months) China

USD Thousands

$847

Japan

Korea

$778

Singapore

$780

USA

$825

$303

Carcinogenicity (Rat, 2 Years) China

India

USD Thousands

$1809

$421

Japan

Korea

$1991

USA2

$1792

$395

Figure 2: Sasaki et al. estimates of early cost estimates of non-clinical safety studies (USD thousands)

10

P h a rm a F o c u s A s i a

ISSUE - 20 2014

organisations (clinical and non-clinical) in Asia Pacific by country as of May 2014. The majority of operating CROs are in the most mature countries: 50 per cent have their headquarters in India, and 18 per cent in China. Japan and Taiwan account for 12 per cent and 6 per cent of total number of companies respectively. Individual company data and was difficult to find and validate.

In 2009, Sasaki, Hinotsu and Kawakami compared the cost of non-clinical safety studies across five Asian countries10. Figure 2 contains a summary of their findings: The United States was included in their analysis as a benchmark. China and India produced the most cost efficient studies overall. However, Sasaki et al further note that in 2009, GLP-generated data from South Korea was the most reliable on account of being a member of the Organisation for Economic Co-Operation and Development (OECD). Moreover GLP labs in the South Korea have passed GLP inspection by the OECD11.

Pricewaterhouse Cooper’s (PWC’s) 2008 report “The Changing Dynamics of Pharma Outsourcing in Asia; Are you Readjusting Your Sights” analysed overall outsourcing risk factors for the Asian countries. The report states that in terms of economic risk, Singapore is the least risky Asian country, followed

by India and China, and then Malaysia and Taiwan. Indonesia, Vietnam and the Philippines are the most risky.12 However, cost is not the only factor when selecting an outsourcing partner.

Non-clinical CROs in Asia offer a breadth of services. The rest of this study 10 Sasaki M et al. Good Laboratory Practice (GLP) status of Asian Countries and its implementation in non-clinical safety studies in pharmaceutical drug development. J. Toxicol. Sci. Vol 34, no 5, 493-500, 2009. https://www. jstage.jst.go.jp/article/jts/34/5/34_5_493/_pdf last accessed May 9, 2014.

11 Ibid.

12 PriceWaterHouseCooper “The Changing Dynamics of Pharma Outsourcing in Asia: Are you Readjusting Your Sites?” October 2008. http://www.pwc.com/en_GX/gx/ pharma-life-sciences/pdf/change_asia_10_08_08.pdf Accessed May 9, 2014.

strategy

Country

Mature services • Integrated discovery services • Internal R&D programs

India

• Clinical development services • Innovation in biology research derived mainly from the government; innovation in chemistry research derived mainly from private sector

• Early-phase drug discovery China

• Large animal pre-clinical development • Innovation in biology and chemistry research derived mainly from the government

Figure 3: A Snapshot of Mature Non-Clinical Research Services offered by Indian and Chinese CROs

Non-clinical services in Asia

In 2013, Jim Zhang took a closer look at China and India.13 He noted that the CRO markets (non-clinical and clinical) in the two nations have different offerings: China’s CROs are most mature with respect to early-phase drug discovery research in addition to pre-clinical development in large animals (e.g. nonhuman primates).

Zhang’s research demonstrated that Indian CROs offer integrated discovery services, as well as internal R&D programmes. Zhang also notes that the Indian outsourcing market is the oldest and most mature in Asia. Indian CROs are thus the most experienced in most of the stages across the drug development R&D spectrum.

The 2008 PWC report echoed Zhang’s findings. PWC’s report noted that China has strong capabilities in pre-clinical trials across many different animal models, while India’s capabilities 13 Zhang JJ. Emerging Outsourcing Destinations.

Chimica Oggi – Chemistry Today. Vol 31(4). July/August 2013 p 18-23. http://www.teknoscienze.com/Articles/ Chimica-Oggi-Chemistry-Today-Emerging-outsourcingdestinations.aspx

are strong mainly in small animal or rodent.14 The PWC report also notes that government institutes provide much of the innovation in biology research in both China and India.

Government institutes also provide the most innovation and capabilities in chemistry research, whereas in India, the private sector contributes many services 15. Figure 3 contains a summary of the key findings of the two reports: Conclusions

This initial study and literature review begins to characterise the size and 14 PriceWaterHouseCooper “The Changing Dynamics of Pharma Outsourcing in Asia: Are you Readjusting Your Sites?” October 2008. http://www.pwc.com/en_GX/ gx/pharma-life-sciences/pdf/change_asia_10_08_08.pdf Accessed May 9, 2014.

15 Ibid.

A u t h o r BIO

focuses on the services offered by the two most mature Asian non-clinical CRO markets: China and India.

structure of the Asian non-clinical outsourcing markets. It also looks to provide a review of the main non-clinical services offered by China and India: Asia’s two most mature non-clinical outsourcing markets. Data from this report should be read with caution, however, as regulatory challenges have not been addressed. Moreover, limited data is available on emerging countries such as South Korea.

The data, although limited, are directionally accurate. The data indicate that Asian non-clinical CROs are poised for growth. Aldrich forecasts that the drug discovery market will grow at a compound annual rate of 16 per cent from 2012 to 2016, reaching US$21.2 billion by 2016 16. The PWC report indicates that China and India will remain market leaders in drug development, along with Singapore17. This initial study is a first attempt to provide high-level metrics to assist sponsor companies in assessing non-clinical service providers in Asia, with specific focus in India and China. Ultimately, the data found in this report and literature review will provide pharmaceutical companies with high-level metrics that will help aid biopharmaceutical companies with non-clinical strategic planning.

16 Aldrich S. Discovery Outsourcing Report: BRIC drug discovery companies lead the market to $11 billion. Contract Pharma. Sept 2012. http://www.contractpharma. com/issues/2012-09/view_features/discovery-outsourcingreport/. Last accessed May 9, 2014.

17 PriceWaterHouseCooper “The Changing Dynamics of Pharma Outsourcing in Asia: Are you Readjusting Your Sites?” October 2008. http://www.pwc.com/en_ GX/gx/pharma-life-sciences/pdf/change_asia_10_08_08. pdf Accessed May 9, 2014.

Stella Stergiopoulos manages multi-sponsored and grant funded research projects at Tufts CSDD. She has experience conducting research on pharmaceutical industry practices and trends affecting pharmaceutical outsourcing practices, cycle time metrics, resource management, and protocol design. She has been a presenter at conferences and has published in peer-reviewed and trade journals.

www.pharmafocusasia.com

11

CPhI P-MEC India

Exploring for solutions, research & technology

If the success story of the CPhI & P-MEC India 2014 show is an indication of things to come, then the $30 billion Indian pharmaceutical industry is definitely poised to storm into the global pharma scene with its entire value chain. The industry exports have already surpassed $15 billion and it is poised to double by 2020.

CPhI & P-MEC India 2014, the three-day premier ‘show of strength’ for India’s pharma industry attracted 27,237 attendees from 94 countries across the globe.

The event witnessed a record participation of 1045 exhibitors from 21 countries and was spread over 55,000 sq. mts. in eight exhibition halls of the Bombay Convention & Exhibition Centre, Mumbai, India thus reinforcing its position as ‘South Asia’s Biggest & Most Comprehensive Pharmaceutical Event’.

From formulations, technology, machinery solutions, contract research, and process developments to packaging – Indian players in pharma and machinery manufacturing have successfully flexed their muscles in the global technology, ingredients, outsourcing and bio-pharma segments. With these plus points, the industry is now looking forward to

12

P h a rm a F o c u s A s i A a

ISSUE - 20 2014

opportunities in globalizing their businesses through the much needed "Brand India Pharma" promotion.

The 2014 edition of CPhI & P-MEC India showcased pharmaceutical ingredients and related products such as Bulk Drugs, Excipients, Biopharmaceuticals, APIs, intermediates and fine chemicals. The roster of participants reads like a ‘who’s who’ list of global pharma industry. While the global pharma giants like BASF, Capsugel Healthcare, Àurobindo Pharma, Merck Millipore, Indoco Remedies, ACG Worldwide, Bosch Ltd., Fette, IMA Industria Macchine Automatiche S.P.A, Marchesini Group, Truking Technology, Waters India, Agilent Technologies, Shimadzu, Thermo Fisher Scientific, Spinco Biotech, WALDNER Laboreinrichtungen GmbH & Co. KG, Fabtech Technologies International Ltd., Mitsubishi Electric India, Cadmach Machinery Co. Pvt Ltd., Thermolab Scientific Equipments Pvt. Ltd., Hetero Drugs Ltd., UK Trade & Investment, DSM, Evonik Degussa India Pvt. Ltd., etc were present in full strength, there was participation from drug manufacturers, machinery manufacturers and importers from countries such as Ghana, Latvia, Afghanistan, Iraq, Burma, etc.

One of the highlights of the show was that high-level delegations from Nepal, Vietnam, Sri Lanka, Korea, Turkey and Egypt had discussed various issues

related to the industry to find out how the two-way trade in pharma can be expanded.

During his visit to the exhibition Mr. Amrasad, Head of Egyptian Pharmaceutical Vigilance & Egyptian Ministry of Health said that, “We have has proceeded and progressed to encourage this industry in India to invest in Egypt. This kind of mutual cooperation and investment is very beneficial to both the sides. We are not just interested in imports of final product but to manufacture the product in Egypt. The focal point to export to the whole Mina region will be a win-win situation for both sides and we will do our best to help this push”.

India is on a major growth path and the authorities are offering required facilities for the overall growth in the pharma industry. Talking about the Andhra Pradesh, the hub of pharma industry in India, Mr. G. Dharmadata, Joint Director, Drugs Control Authority of Andhra Pradesh, during his visit to CPhI & P-MEC India 2013 said “We are proposing two more SEZs for the pharma industry in the state to provide major boost to the exports of bulk drugs.” Andhra Pradesh boasts of 25 per cent of the country’s USFDA manufacturing facilities and it is planning further major expansion.

Commenting on the overwhelming response the exhibition received from leading Indian and foreign companies, Joji George, Managing Director, UBM India Pvt. Ltd. highlighted the unprecedented interest on India by global pharma industry. He stated that, “It is no longer that India is considered as a mere destination of low-cost manufacturing and low-end

bulk drugs. The profiles of international participants reflect that everyone from all known markets across the globe is interested in India. Indian and foreign participants are so keen to leverage CPhI & P-MEC India to grab the opportunity. It is the bus that no one wants to miss”.

CPhI P-MEC India 2014 will be held from 2 - 4 December 2014 at Bombay Convention and Exhibition Centre, Mumbai, India.

Honoring, rewarding and celebrating excellence in the pharma industry!!

UBM India proudly announced the 2nd annual UBM India Pharma Awards on the 1st December 2014 at The Westin Mumbai.

The event, more than an ‘Awards Night’ is a celebration of the coming together of the luminaries and harbingers of the industry. It is night of glamour, entertainment, celebration and of course, the pride of being the crème de la crème of the Indian Pharmaceuticals Industry!

The UBM India Pharma Awards provides a platform to demonstrate organizational capabilities in the direction of Innovations in 10 different categories on this most leading industry platform. The event is attended by the who’s who from the Pharma industry, policy makers from the country as well as Asia and Europe.

As the Pharma industry is increasingly looking towards India for higher quality, low cost Pharma solutions, the UBM India Pharma Awards is the perfect place for companies to engage with the movers and shakers in India’s Pharma machinery, technology, ingredients, outsourcing and BioPharma industry.

Read more: www.indiapharmaawards.in Advertorial

www.pharmafocusasia.com

13

strategy

Pharma Outsourcing

Facing significant challenges To respond to pressures like skyrocketing development costs, uncertainty around regulatory and reimbursement, patent cliffs, generic erosion, and a sluggish global economy, biopharmaceutical companies have been changing the way they approach virtually every aspect of their business, including R&D. Adam Dion, Analyst, Industry Dynamics, GlobalData, US

What are the drivers behind pharma outsourcing and how are they changing?

Currently, the pharmaceutical industry is facing some significant challenges. The blockbuster era is over, development costs are skyrocketing, uncertainty around regulatory and reimbursement, patent cliffs, generic erosion, and a sluggish global economy all have industry executives losing sleep at night. To respond to these pressures, biopharmaceutical companies have been changing the way they approach virtually every aspect of their business, including R&D. To remain competitive, drug makers are intensely focusing on generating more value and productivity from every dollar spent on R&D. The challenge of accelerating pharmaceutical product development while also controlling costs creates a difficult balancing act for industry executives. Through the use of strategic outsourcing with third-party vendors, drug makers can maximise their internal resources while at the same time enter into risk-sharing agreements with CROs to generate significant cost savings.

Adam is an Analyst in the Healthcare Industry Dynamics Team at GlobalData. He is an author of GlobalData’s PharmaLeaders benchmark reports, which rank the competitive positions of the top companies in the pharmaceutical, biotech, and CRO/ CMO sectors. Adam received his B.S. in Neuroscience from Merrimack College, and M.S. in Marketing from the University of New Haven.

14

P h a rm a F o c u s A s i a

ISSUE - 20 2014

Why are certain areas, like R&D and clinical trials getting outsourced more, and which countries are benefiting from this?

One of the fastest-growing emerging markets for clinical trial work outside China is South Korea. According to Outsourcing-Pharma.com, the number of clinical trials initiated in South Korea increased from 206 in 2006 to 513 in 2009: a 150 per cent increase over the four-year span (Outsourcing-Pharma.com, 2010). While Korea’s pharmaceutical industry is competitive in terms of chemical and synthesizing technologies, it is considered

strategy

less competitive in drug screening, safety evaluation and clinical development. Companies have therefore found partnering to be an ideal way of becoming more involved in R&D. The increased investment in South Korea is not only coming from outside the country. The government is also putting forward initiatives to spur investment dollars into the country’s clinical trials market. One government initiative is the Korea National Enterprise for Clinical Trials (KoNECT), a collaboration between the South Korean government and a number of global Contract Research Organizations (CROs) to provide life sciences groups with clinical resources, training and support. Icon and KoNECT will collaborate on a series of educational events for local and multinational pharmaceutical companies, investigators and industry executives. Programs will aim to further enhance the already high standards for clinical research in South Korea, including creating therapeutic-focused seminars.

In addition to KoNECT, the Korea Drug Development Fund (KDDF) is a consortium of three health-related Korean ministries established to help Korean drug companies develop and commercialise healthcare products for the global market.

With assets approaching US$1 billion, KDDF was established in September 2011 to develop at least 10 new drugs by 2019 for the global pharmaceutical market.

The emerging markets in Europe, the Middle East and Africa (EMEA) have become attractive regions for pharmaceutical outsourcing due to easy access to large treatment-naïve patient pools, low labor and manufacturing costs and highly skilled medical research talent. In fact, the population of Central and Eastern European countries exceeds that of either the US or the five largest Western European markets combined. Furthermore, there is a lower saturation of competing trials within the region compared to other, more developed markets, and recruitment and retention are also strong. However, due to regional differences in commercialisation and regulatory pathways, the need to partner with local clinical trial expertise is a critical plank in any pharmaceutical company’s globalisation strategy.

After the fall of the Iron Curtain more than 20 years ago, countries such as Russia and Poland arose as outsourcing hot spots in Europe, however the clinical trial market has been stagnant there during the last decade. Now, thanks to the mercilessness of the patent cliff and maturing drug markets in the US, Japan and Germany, pharmaceutical companies are searching for opportunities in Central and Eastern Europe for renewed profit generation and to grow market share. As a result, CROs are following their pharmaceutical brethren into EMEA, which has led to an increase in deals activity and infrastructure investment into the region. The larger presence in countries such as Russia will help CROs to expand both their client lists and revenue bases.

How is the nature of outsourcing in Asia changing?

What are the key challenges Asia needs to address?

Asia is a mixed bag of tricks with each country having its own internal dynamics. Countries such as China, Taiwan, Singapore, Korea and Vietnam have become important destinations for conducting clinical trials. Singapore, for example, is often considered the nucleus for clinical research in the Asia-Pacific region. With mainland China and the Korean peninsula to the north and Australia and Oceania to the south, it is a natural hub for clinical outsourcing. The government of Singapore promotes translational and biomarker research and has put in place laws protecting intellectual property. It also adheres to Good Clinical Practice (GCP) guidelines, offering a sense of security and assurance to pharma clients looking to conduct trials in the country. However, with a small patient pool, clinical trial opportunities in Singapore (and other small countries) are limited to mostly Phase I/II trials, leaving the heavily populated countries (China) to grab the bulk of late-stage trials where large patient numbers are required.

The Chinese CRO market has been rapidly growing over the last few years as Big Pharma looks to tap into the region’s burgeoning drug market. However, pharmaceutical companies and service providers are entering China (and certainly India) with tepid hesitation, and for good reason. Both countries have lax standards around patient safety, which is concerning to pharmaceutical companies looking to conduct clinical trials. While both India and China offer access to large pools of treatment-naïve patients and cheap labor, each country’s regulatory structure lacks the transparency seen with the US and EU agencies and are riddled with hurdles. China and India offer byzantine regulatory regimes, making each country far more complicated than originally thought. As a result, the labor savings in China and India are commonly juxtaposed with longer approval timelines for bringing a drug to market. This is beginning to change how pharmaceutical companies and CROs do business in these countries.

India is a different story. Demand for conducting clinical trials in India has essentially evaporated as pharmaceutical companies wait on the sidelines for it to overhaul its regulatory framework in light of the some 400 clinical trial deaths reported in 2012, a number many watchdog groups attribute to the country’s lax regulations. However, the government has begun to put in place policies to start rebranding its image for conducting clinical research. It is in the process of establishing independent ethics committees similar to those which exist in the US and in Europe, and regulators are pushing for the requirement of studies to be conducted in GMP-compliant facilities that are on file with regulators, and subject to random inspections. Time will tell if these measures are robust enough to reintroduce confidence to the system, but until then, pharmaceutical companies will have a wait-and-see approach.

www.pharmafocusasia.com

15

strategy

16

P h a rm a F o c u s A s i a

ISSUE - 20 2014

strategy

Healthcare reforms have moved from saving costs to initiatives focused on improving health outcomes and sustainability.

This article explores ways in which pharmaceutical companies can transform their businesses to demonstrate that they can bring new value to healthcare systems.

Patrick Flochel, EY Global Pharmaceutical Sector Leader, Switzerland

I

n countries around the world, healthcare spending continues to grow at an unsustainable rate. As a result, a growing priority for governments today is increasing the effectiveness of their healthcare systems. Many countries, from the US, parts of Europe and Japan to fast-growing markets such as China and India, have made healthcare reform a top priority.

Initially, the primary objective of most healthcare reforms has been to contain costs. But, more recently, policymakers have taken new initiatives to improve the sustainability of healthcare systems, looking beyond cost considerations to population health.

Spending on drugs has been a highly visible target for cost containment. But, as it weathers short-term cost-cutting initiatives, the pharmaceutical sector is being presented with clear opportunities to prove that it is able to bring value to healthcare systems.

The fundamentals of the pharmaceutical industry are strong. In most countries, years of better care and nutrition have led to ageing populations, expanding the potential patient base. Meanwhile, rising incomes in emerging countries are boosting demand for higher-quality healthcare. These trends are underpinned by an ongoing surge in the prevalence of chronic diseases, such as cancer, diabetes and heart disease, which require longterm treatment.

But pricing and regulatory challenges, among others, have put the industry’s traditional business model ‘Pharma 1.0’, if you like under tremendous pressure.

As a result, it is being forced to become more innovative, collaborative, diversified, global and value-driven. Today, most pharmaceutical companies are in the process of transforming their businesses along these ‘Pharma 2.0’ lines. This transformation has an impact on all aspects of pharma companies’ operations.

Pharma 3.0

Just as the industry began to embark on its Pharma 2.0 journey, new and sweeping trends are again transforming the business environment. Changing incentives are reshaping the healthcare ecosystem, as policymakers realise that in a sustainable value proposition, health outcomes are the most valuable currency. This shift will, in turn, require the pharma industry to also develop business models focused on health outcomes, where the traditional product a drug is only one part of pharma’s value proposition.

Health outcomes

In an outcomes-focused healthcare system, stakeholders will be rewarded for the perceived value they deliver to the system. Information technology is a major enabler of this kind of approach.

Digitalised health data, electronic health records and associated platforms offer

www.pharmafocusasia.com

17

strategy

The

science

Patents Pricing pressure Compliance commitments

The

Impact of change

customer

Reduced growth Margins squeezed Reputation in decline

Globalization Customer redefinition

The

Products vs. services Building brand

The

Talent pipeline Celebrating diversity

offer people The

organisation

R&D productivity Commercial structure Customer relationships

R&D productivity Personalized medicine

The

value created

Enterprise vs. expertise Alternative business module

Return vs. revenue Financial strategy Risk management

Figure 1: Business model transformation: Pharma 1.0 to Pharma 2.0

the promise of enhancing efficiency, increasing safety and reducing costs.

Mobile health technologies provide live and real-time access to health information, supporting diagnosis and monitoring, as well as driving compliance in medication.

This tremendous expansion of availability of health data is empowering payers to implement outcomes-based pricing and reimbursement. The same transformation is happening on the patient side. The convergence of social media and health information means that we are empowered to improve our health, with access to information that, in the past, was available only to our physicians. Traditional patients are becoming ‘super consumers,’ capable of making real, value-based decisions based on their health outcomes.

These shifts are attracting many non-traditional players, including e-health and mobile health firms, consumer electronics companies, large retailers, medical technology

18

P h a rm a F o c u s A s i a

ISSUE - 20 2014

firms and information aggregators.

At EY, we recently surveyed business development and innovation leaders and found overwhelming agreement that these new entrants will play an increasingly important role in the health outcomes ecosystem.

What can pharma do to prove its value in this new, complex environment?

If it is to deliver on health outcomes, it will have to engage in the cycle of care around the patient, from predisposition testing, prevention, diagnosis and therapy to patient monitoring. The industry’s 2.0 business model is not equipped to deliver on such a value proposition. To move to 3.0, it will need to collaborate with non-traditional players and co-create value for patients, payers, governments and business partners. Pharma companies seeking to deliver health status improvements need to reach new patients by tackling underserved markets, meet unmet medical needs and do a better job of serving existing patients by managing

patient outcomes. Their business models will need to combine three core value propositions: 1. Managing patient outcomes by, for example, fostering compliance through patient engagement, or engaging in healthcare delivery either directly or by enabling a more targeted delivery through patient population stratification.

2. Expanding access to healthcare in underserved markets, in developing countries and in more mature markets for uninsured patient populations. Examples of collaborations to expand access include partnerships between pharmaceutical companies, governments and/or non-profit organisations.

3. Meeting unmet medical needs in complex indications such as oncology or immunology as well as in underserved therapeutic fields such as malaria, dengue fever and orphan diseases.

strategy

19

P h a rm a F o c u s A s i a

ISSUE - 20 2014

strategy

product development lifecycle is notoriously long. In the new ecosystem, the business environment is rapidly evolving, as new technologies appear almost daily.

These are all valid obstacles to change. But the industry can overcome them by taking a ‘commercial trial’ approach, leveraging and reimagining some of the things they do best. Many of these initiatives are now under way at all levels of the industry.

• Pilots: Once a company has identified a strategic area on which it wants to focus, its next step should be to identify different ways in which it can play in that space and to test those in early pilot versions.

• Rapid prototyping: Succeeding in the future will mean ending failing experiments and leveraging lessons

Business model innovation

We have found that pharma executives understand the new business environment, but there is resistance to adapting business models to suit. Three main challenges have emerged in our conversations: • The current business model is working. It is still delivering high margins and solid growth in its current configuration and is expected to continue to do so in the short or mid-term.

• The industry will need to explore uncharted territories to develop business models around health outcomes.

Companies will need to develop partnerships with players from other industries, which are beyond their current comfort zone.

• The ecosystem is changing too quickly for pharma to respond. The industry’s

Drivers of change

R&D productivity Patent cliff Globalization Demographics Pricing & reimbursement

Business models Pharma 1.0

Blockbuster drugs

Healthcare reform Health IT Consumerism Value mining

Pharma 2.0 Diversified drug portfolios

learned through rapid prototyping.

This will require new cultural mindsets that provide incentives for speed, flexibility and experimentation.

• Open innovation: Delivering new outcome-based products and services will require combinations of competencies that no firm possesses in-house.

Companies will need to bring an outside-in, open approach.

• Flexible contro: Alliances will need to be sufficiently well-defined to maintain the focus of the collaboration but flexible enough to allow for quick response to new challenges and opportunities.

• Portfolio management: Companies will need to look across their alliance portfolios so that partners can learn from each other, identify synergies and increase the overall value they deliver.

Pharma 3.0 Health outcomes

Customer Patient Physician Payer

Figure 2: From products to outcomes

20

P h a rm a F o c u s A s i a

ISSUE - 20 2014

strategy

Guiding principles for Pharma 3.0

Transformation is an evolutionary process. Each business model fuels the next. Pharma 1.0 is still a highly successful model that has driven the industry’s growth, producing margins unmatched by other sectors. Pharma 2.0 has helped the industry change its approach to customers, alleviating some of today’s pressures and laying the ground for Pharma 3.0 and a collaborative, outcomes-centered perspective.

Depending on each company’s strategy, these models may co-exist at different times. But as companies begin to embrace the changing ecosystem with strategies to derive new growth, we propose four guiding principles to successfully capture the Pharma 3.0 opportunity.

1. Define your Pharma 3.0 brand: The ecosystem is becoming more complex, incentives are changing, and nontraditional players are entering the market. To define your brand in the new environment, ask yourself these questions: • Are your front-line executives focused on these trends • How will these changes impact your business • What is your strategic focus, and what will be your competitive advantage in this more complex reality?

2. Co-create value with partners and patients: More than ever, firms will need to combine unique assets and attributes to build relevant offerings for the outcomes ecosystem.

3. Experiment, think small and fail fast: There is no single right answer. Companies will develop solutions by experimenting with large numbers of ‘commercial trials,’ and culling those that don’t work.

• How well does your organisation encourage experi mentation and ‘outside-in’ learning? How well does it accept failure as an inevitable by-product • How much are you investing in business model innovation (versus product innovation) • How rigorous is your pipeline of commercial trials for business model innovation?

4. Prepare for success: Our experience tells us that pharma companies aren’t fully prepared for the challenges that these creative new alliances will bring. Some of the questions that need to be answered include: • What gaps do you have in your skill sets and capabilities, and what are you doing to fill them • How are you monitoring and addressing the new and heightened risks in Pharma 3.0 deals • Have you identified and empowered a leader for business model innovation?

The life sciences industry is already good at traditional R&D collaborations with peers or biotech. Partnering with non-traditional players from other

A u t h o r BIO

Pharma 3.0 represents a significant shift from Pharma 2.0’s ‘contractual’ collaborative approach, where pharma companies have been in the driver’s seat in managing collaborations with business partners and controlling and commercialising most of the value creation. So to succeed in Pharma 3.0, companies will need to step outside the familiar and relinquish control, combining capabilities, resources, channels and customer relationships with those of their business partners.

• How open is your (business model) innovation • Are you focused on being a partner of choice for nontraditional players • What is your network strategy to become a critical player by intentionally co-creating value for partners and patients?

industries, such as technology, insurance, internet services, food and retail, may require assimilating a host of differences in operations and cultures.

Patrick is responsible for EY's strategy, thought leadership and branding, learning and network development to best serve our clients in the life sciences industry globally. Patrick also serves as the global client service partner or as senior advisory partner on a number of European pharmaceutical clients. He has served on various management and leadership positions at E&Y at global and EMEIA levels.

www.pharmafocusasia.com

21

R&D

Developing New Vaccines Novel approach and standardised methodologies In theory, there exist almost infinite number of potential vaccine platforms. In addition, for each such platform, there are many different possible engineering that could lead to different vaccine properties. So, how these be compared? The answer in part lies in standardisation of the process.

David Klatzmann, Professor, Laboratory of Biology and Therapeutic of Immune Diseases, University Pierre and Marie Curie, France

22

P h a rm a F o c u s A s i a

ISSUE - 20 2014

E

dward Jenner’s work in developing the world’s first smallpox vaccine in the 1790s demonstrated that it was possible to protect the general population from major threats to public health, and vaccine development aimed at combating the major concerns of the day has continued ever since. There have been many successes, and vaccines are now available to immunise people against a wide range of diseases, including measles, polyomyelitis, smallpox and tetanus.

However, the pace of vaccine development over time has been extremely uneven a situation that, given the severity of the health threats currently facing the world, demands to be addressed.

The resulting need for a more systematic method of vaccine development has led directly to the development of the CompuVac (Rational Design and Standardised Evaluation of Novel Genetic Vaccines) project.

R&D

Our initiative which brings together 19 mainly European institutions in the search for a more effective approach to the issue is pursuing an ambitious set of objectives very much in line with the pressing nature of the problem. Indeed, this project aims to develop methodologies and tools to improve vaccine development, notably through standardisation of vaccine evaluation.

What the process comprised

(i) a large panel of vaccine vectors representing various vector platforms and all expressing the same model antigens; (ii) standardised methodologies for the evaluation of T- and B-cell responses and of molecular signatures relevant to safety and efficacy; (iii) a database for data storage and analysis of large data sets; (iv) intelligent algorithms for the rational development of prime boost vaccination.

As things stand researchers who want to develop a vaccine platform—or to

improve their existing vaccine—usually take their own vector and introduce their own antigen of choice into it.

Typically researchers then test it with their own methodologies. While the initial response to this kind of work may well be extremely enthusiastic, the longterm picture is rather more complex. In particular, the absence of standardised procedures mitigates against the accurate, effective evaluation of vaccines.

The problem is that people rarely, if ever, compare what they are obtaining with the results of others obtained with different types of vectors. This means the direct comparison of vaccines’ potential is extremely difficult. In order to allow for the comparison of results you have to first establish methods that will provide significant grounds for it.

The idea here is first to have people use the same antigens to measure immune responses. Within the project we choose two so-called ‘model antigens’—one for

testing cellular immune responses and the other for testing humoral immune responses—which are the two halves of the human immune response to vaccines.

The next step was then to standardised procedures to evaluate immune responses to these two antigens. The need for sophisticated new methods is made even more pressing by the modern advances in medical science, which have established new parameters in vaccine development.

Great advances have been made over recent times, advances which prompt us to say that we are living through a particularly important period in the history of vaccine development.

There are so many potential vectors out there. Nowadays, people are realising that they can use virtually any type of virus or even bacteria to establish a platform for the expression of heterologous antigens and turn this into a vaccine. They can likewise use the ability of our body to respond to a certain

www.pharmafocusasia.com

23

R&D

24

P h a rm a F o c u s A s i a

ISSUE - 20 2014

The need for sophisticated new methods is made even more pressing by the modern advances in medical science, which have established new parameters in vaccine development. to get these people to work together and really understand each other. We did this by also recruiting some scientists with training in both aspects ­—biomathematics and immunology—who acted as ‘translators’ so as to help us discuss the relevant issues. If there has been a breakthrough then this is it—it brings together people from two different worlds and makes them work together to generate a meaningful database. By our commitment to making their results publicly available, the CompuVac project has added another dimension to this initiative. Indeed, their data provides an extremely solid foundation for further research, and as such the project’s work has already attracted the attention of a number of other interested parties.

The first three years of the project were really devoted to building our own vaccines, testing them and developing the database. All this preliminary work has been done and it’s provided us with proof of concept and really showed us that we can generate a meaningful comparison. We’re just starting to publicise our efforts and have already met with some success. For example, we have had contact

A u t h o r BIO

virus or bacteria to make it respond to something else. So there is, in theory, an almost infinite number of potential vaccine platforms. In addition, for each such platform, you have many different possible engineering that could lead to different vaccine properties. So, how are you going to compare these? The answer in part lies in standardisation of the process.

Developing a standardised means of comparison is clearly no easy task, and a number of significant questions remain unanswered. However, it is a task that CompuVac’s advanced technical expertise undoubtedly makes the project well-suited to. Two so-called model antigens that are very well-known have been selected; these are antigens for which there are extremely good, well-known methodologies for immune response evaluation. We have put great efforts into standardising methods for evaluating immune responses against these antigens. There is no magic wand here—it’s just standardisation. The challenge is to get the people developing vaccines to agree to use these methods and then to compare their vectors with those of others.

One of our main goals is to make publicly available this whole system and a database of results obtained with it.

People will be able to test their vaccine design with the gold standard antigens and standardised methodologies, go into the database and compare their results to those already there. Establishing this kind of database has proved to be a complex undertaking. Quite apart from the technical complexity involved, the fact that information technology and immunology are two very contrasting disciplines has added another layer of difficulty. It was very challenging for us to bring computer scientists together with immunologists, because these really are two very different worlds.

Computer scientists are often not very well-informed about immunology, and many immunologists don’t know much about databases and all the specific things surrounding that. The real challenge was

with academic researchers, non-profit organisation as well as biotech companies.

They are extremely interested in using our methodologies to advance the development of their products. This kind of response gives some idea of the potential of the CompuVac project. While such interest is of course welcome, it will not distract him from the day-to-day concerns of pursuing the project’s primary objectives. The next goal for the coming year is to present our results. A couple of meetings have already been planned to present and promote CompuVac, and we will try to get the vaccine community to accept this standard and then encourage them to contribute to its further development. We need to find sponsors for the sustainability of the project. They will agree to maintain the database available on the web for free access by researchers. Sponsors could comprise a charity, a company, or an academic institution.

A unique set of vaccines of different classes has now been assembled and compared, from viral vector derived vaccines to inert VLPs. The validated database and the tool box will be made freely available to the scientific community at the end of the project in June 2009.

A conference in Paris will be held on the June 29th of 2009, with international experts in vaccine development.

This will be the occasion to present the results of such an evaluation and how it was translated into the development of an HCV vaccine, but also to donate the database and tools to our sponsor(s), and to organise the final communication which should help the CompuVac approach to become an accepted standard in vaccine development.

David Klatzmann is a professor of Immunology at the Pierre & Marie Curie medical school. He is the Director of the ImmunologyImmunopathology-Immunotherapy Lab and the head of the Biotherapy department at the Pitié-salpêtrière hospital and medical school. His main activities have been to develop translational research in Immunology, he built-up a global organisation – research unit and hospital department – which is one of the rare structure capable of developing biotherapies from bench to bedside.

www.pharmafocusasia.com

More than

190,000 READERS in pharma industry across the globe.

Frequently preferred pharma magazine, a leading brand name, a source of information with latest breakthroughs and trends in the industry, with huge subscriber database that leads you to the best promotions in the market. Focuses on Strategy, Research & Development, Clinical Trials, Manufacturing, Information Technology. Available in online version.

HannanDesignStudio.com

We Brand the Future. We create Dierence.

Hard-copy Subscriptions: Email: info@pharmafocusasia.com Tel: + +91 40 4961 4567 Media Contact: Email: advertise@pharmafocusasia.com Tel: +91 40 4961 4567 www.pharmafocusasia.com

25

Clinical Trial

Issues & Concerns in Conducting Clinical Trials in India high costs involved, drug companies are constantly exploring ways to outsource clinical trials to countries that provide services at lower costs and more efficient timelines. India, due to its large patient population and genetic pool, can provide both cost-savings and speedier trials.

In addition, India’s adoptions of ICH compliant regulations governing clinical trials further its constant endeavor to take its regulatory regime to global standards.

Regulatory concerns

Issues like approval delays, deficiencies of functioning of CROs and other stake holders, liabilities and compensation to injured subjects, insurance issues etc still remain in India, which has made multinational companies to rethink on opting for India to conduct clinical trials in India recently. There is a need for a law to ensure that the people who undergo clinical trials are not exploited and should be well informed about risk as well to provide clarity on regulations.

Milind Antani, Head, Pharma & Life Science Practice Group, Nishith Desai Associates, India Gowree Gokhale, Partner, Nishith Desai Associates, India

I

ndia’s strong value proposition has enticed multinational pharmaceutical companies to enter into or significantly expand existing operations in India in the fields of drug discovery, contract manufacturing and clinical research. In 26

P h a rm a F o c u s A s i a

ISSUE - 20 2014

addition to huge internal market potential, India presents an attractive destination for drug companies seeking to minimize cost, while enhancing efficiency and adhering to international standards of quality for clinical research. Due to

Although regulations relating to clinical trials have evolved considerably to match global standards, many issues still remain. There are several grey areas in the regulations that need to be clarified.

Hence, often for several issues, authorities need to be consulted or the industry practices need to be ascertained.

A major concern a foreign sponsor faces in India is the extreme shortage of regulatory experts. Unlike FDA and EMEA, DCGI does not release guidance documents providing the current interpretation of the regulations. Since the regulations described are meant to be general, their interpretation is highly subjective and based upon the experience of the regulatory consultants. It is not uncommon to have several experts come to different conclusions about the same regulation.

The sponsors should be aware of differences in the Indian GCP version of

Clinical Trial

ICH-GCP, including the Indian specifications for the composition of the Ethics Committee, informed consent procedures, compensation for participation, as well as the roles and responsibilities of foreign sponsors conducting clinical trials in India.

At present the regulations do not permit first-in-man studies (Phase I) for drugs discovered outside of India.

More recently, there have been some discussions by the Indian government to consider removing this constraint and update schedule Y to be more consistent with US and ICH guidelines.

members of the ethics committees across the country to improve the functioning of IEC, in collaboration with WHO, ICMR and many committed research professionals.

The Deficiencies in the functioning of the ethics committees and CROs

Approval process

There are several CROs that carry out trials on behalf of the sponsors. However, it has been noticed that some of the CROs lack adequate infrastructure and knowledge. Hence, it is advisable to carry out appropriate due diligence of CRO before appointment.

It has been observed that many clinical research institutions in India have an inadequate representation of the nontechnical personnel in Institutional Ethics Committee (IEC). Without adequate representation of persons from a nonfunctional background, the opinion of the IEC is likely to be unfair and biased in favor of the clinical study. The clinical research guidelines clearly specify the need for such personnel in the IEC. Some institutes have IEC but do not have a regular schedule of committee meetings, lack Standard Operating Procedures (SOPs) or do not have a proper member representation according to the ICMR guidelines.

However, things are changing fast for the better. New Schedule Y1 is proposed which has mandated registration of CROs with the authorities and only these registered CROs will be allowed to manage clinical trials. The Central Ethics Committee on Human Research (CECHR) by ICMR audits the functioning of these IECs composed as per the ICMR guidelines. The DCGI’s office has been conducting training programs for

Clinical trial liabilities

The sensitivity of the clinical trial in view of the involvement of human subject can be well understood and appreciated. The human subject can either be healthy volunteers or patients suffering from disease for which the drug is being tested. All the stakeholders involved in

conducting the trial have significant exposure to liability. Generally, the targets for litigation are the investigators and the institution involved. The company that sponsors the trial is also exposed to the risk of liability on account of improper disclosure, conflict of interest, violation of good clinical practices, injuries occurring due to the test drug.

Not many cases have reached courts in India, however, the awareness amongst patients is certainly increasing.

Further, there are certain NGOs that take up the cause of study subjects.

The approvals in relation to clinical trials and import of study drugs are regulated by Central (Federal) law and regulations. The approvals for the same are granted by the Drugs Controller General of India (DCGI). The approval process may take 4 – 5 months. Unlike in the US, where a sponsor can proceed with a clinical trial 30 days after submission of an IND application if FDA has not commented, in India, the sponsor or its agent in India must receive written approval from the DCGI to proceed with a clinical trial. For global trials, a delay in getting DCGI approval could mean Indian sites lagging far behind sites in other countries for the same study. The shortage of adequate number of skill staff lead to delays in getting approval from the DCGI’s office. However, new DCGI has been making all the efforts to expedite the approval process.

Depending on whether the study drug is categorised as a biologic or a genetically engineered product, additional approval from other agencies such as the Indian Council of Medical Research (ICMR), the Genetic Engineering Approval Committee (GEAC), and the Department of Biotechnology (DBT) is necessary and can take up to six months or even longer time. Submission to Ethics Committees can be done simultaneously.

The registration of the clinical trial with the Clinical Trials Registry-India (CTRI), has been made mandatory by the DCGI has since 15th June 2009.

Registration of the trial with CTRI involves declaration and identification of trial investigators, sponsors, interventions, patient population etc before the enrollment of the first patient in the clinical trial. Approval by the Ethics committee and DCGI approval are essential before registration of the trial with CTRI. Another major concern is lack of pre-IND meetings with the regulatory reviewers due to the extremely heavy workload, though they are granted on a case-by-case basis.

All indications are that the office is very aware of the issues and working hard to resolve them. The next year or two should be interesting for those tracking Indian regulatory processes.

www.pharmafocusasia.com

27

Clinical Trial

28

P h a rm a F o c u s A s i a

ISSUE - 20 2014

India’s adoptions of ICH compliant regulations governing clinical trials further its constant endeavor to take its regulatory regime to global standards.

envisages imprisonment of five years, and fine of Rs. 20,00,000 for those found violating norms of clinical trial.

Access to drugs

Another issue that arises is the liability of the sponsor to provide access to drugs and treatment post termination of the trial. Depending upon the study protocol, availability of the drug and stage of the trial, this issue needs to be addressed.

Need for the law

cal trial agreements entered into between the parties.

Another factor that plays significant role in the compensation is insurance.

Unfortunately, unlike in other countries, clinical trial-related insurance is not well developed in India. The common practice with regards to insurance is that medical professionals are covered under professional indemnity insurance scheme provided by various insurance companies.

But this insurance cover does not protect medical professionals for compensation of claims arising out of their participation in clinical trials.

Government of India has proposed a comprehensive legislation called Central Drug Authority (CDA) Bill - that

A u t h o r BIO

Liabilities are likely to arise due to breach in “informed consent” rules or adverse reactions due to drugs, negligence of institution or investigator. Typically, the clinical trial agreement allocates the liability among sponsor, CRO, investigator / institution.

As far as sponsor’s responsibility for compensation for an injury related to the study drug is concerned, it would depend on the description of the ‘study’ specified in the Study Protocol (“Protocol”) and the Informed Consent Form (“ICF”). As per the regulations, the primary responsibility is that of the sponsor to provide compensation for any physical or mental injury arising out of a clinical trial OR provide an insurance coverage for any unforeseen injury. In relation to an injury to a study subject arising out of any act, omission, negligence or misconduct of the Clinical Research Organization (“CRO”) / investigator / institution, typically, the sponsor covers itself by contractually obtaining an indemnity from the CRO / investigator / institution, as the case may be. At times, the CRO / investigator / institution also insist on contractually obtaining an indemnity from the sponsor for liability arising out of administration of the study drug as per the Protocol. These indemnities are usually obtained over and above the insurance coverage, if any, taken by the parties for the purpose of any unforeseen injuries.

Recently DCGI has been instructing sponsors /CROs to include the wording in ICF that sponsor or CRO will provide complete medical care as well as compensation for the injury.

The injury may either arise out of the ‘study’ ie as specified in the Protocol and the ICF or may arise out of any act, omission, negligence or misconduct of the CRO or the investigator / institution. The question that arises, therefore, is - who would primarily be liable to compensate the study subject, whether the sponsor or the CRO or the investigator / institution in connection with the study? Usually, as stated earlier, this liability allocation is covered in the clini-

As of today there is no Act or Law to monitor clinical research and drug trials in the country. Such a law is necessary to ensure that the people who undergo clinical trials are not exploited and should be well informed about risk. Indian Chapter of Association of Clinical Research Professionals (ACRP) has been launched.

There is need to enhance capacity building to handle trials in a more scientific and rational way. The likely enactment of law and launching of the Chapter will bring in more professionalism. Indian government needs to bring regulations regarding conduct of clinical trials in India match to global standards and bring in lot of clarity in regulations and speed in licensing procedures. However, the government is aware of this and has been making serious efforts to accomplish the same.

Milind Antani heads the Pharma and Life Sciences Practice at the multiskilled, research-based international law firm, Nishith Desai Associates. Dr. Antani received a Doctorate from Baroda Medical College, Vadodara, Gujarat and a Bachelor of Law from Sardar Patel University, Vallabh-Vidyanagar, Gujarat. His practice areas include Pharmaceutical, Life Sciences, Healthcare, Intellectual Property and Medical Devices. Dr Antani is also the member of FICCI, National Pharmaceutical Committee, FICCI-Gujarat Health care committee and the Committee of Telemedicine Society of India.

Gowree Gokhale heads the IP, technology, media and entertainment law practice of the multi-skilled, research-based international law firm, Nishith Desai Associates (www.nishithdesai.com). She is specialized in litigation and dispute resolution, franchising, pharma and life sciences laws, commercial laws, HR laws. Ms. Gokhale is a Solicitor and a registered Patent & Trade Mark attorney and has been practicing for the last 14 years. She is a visiting faculty at Institute of Intellectual Property Law Studies at Mumbai. She has authored research reports and articles on variety of subjects and has presented at various national and international seminars and conferences on IP, pharmaceutical, media and technology laws.

Nanomilling for Pharmaceutical APIs

The NETZSCH DELTAVITA® Mill

More than 90 per cent of drugs approved since 1995 have poor solubility, poor permeability, or both. Drug performance can be improved by reducing the particle size and at the same time increasing the specific surface area of the Active Pharmaceutical Ingredients (API). Therefore, however an API is administered – in tablet, capsule, powder, or liquid form – small particle sizes offer exciting advantages for pharmaceuticals.

Known benefits include improved dissolution rate, increased bioavailability and higher activity, lead-

ing to lower dosages and a lower risk of side effects for the patient. Reducing drug particles to nano-size increases their surface area, and subsequent solubility dramatically.

The NETZSCH DELTAVITA® mill has been specially designed to efficiently increase solubility of APIs, thereby enhancing their efficacy. Through the efficient use of energy, high flow-rate, multiple-pass grinding strategy, DELTAVITA® mills achieve excellent repeatability as well as homogeneous dispersion. DELTAVITA® mills are fast, extremely versatile and designed to produce a very narrow range of ultra fine particles in a homogeneous formulation. Specific energy reductions of up to 30 per cent can be realized.

With the DELTAVITA®, users can achieve consistent particle size distributions below 100 nanometers to increase surface area, solubility, and bioavailability.

Nanometer-scale particles provide many advantages.

Gene and vaccine delivery becomes more targeted, as well as the development of particles which cross the blood brain barrier. Nanoparticles can enhance the properties of time release molecules, and nanoreceptors can be added to drug surfaces to release drugs exactly where needed.

As for different models, the DELTAVITA® 15-300 is designed with growth and flexibility in mind with several available and interchangeable chamber sizes in stainless steel and ceramic construction. The laboratory series sizes range from 15 to 300 ml chamber volumes. The pilot series is the DELTAVITA® 600 which offers 600 ml chamber volume. In the production series, NETZSCH offers models from 2,000 to 60,000 ml. DELTAVITA® systems are available in portable and permanently mounted-through-wall installations. Each machine is designed specifically for your process requirements. www.netzsch.com/deltavita Advertorial www.pharmafocusasia.com

29

information technology

IT Clouds in life sciences Key to long term sustainability Cloud solutions offer immediate returns in improving operational performance and reducing costs. Multiple approaches to cloud solutions will be needed to satisfy life science industry needs, complicating the development of a coherent cloud strategy.

P

atent expirations and their associated loss of blockbuster revenues across the life science industry have forced companies to take a hard look at ways to improve operational efficiency. As part of a deep introspection that has never before been considered, companies are critically assessing which activities are truly core to the business and which activities can be performed more efficiently by a partner. IT infrastructure is clearly an area under review and it is becoming clear that some, if not all of this activity can be performed more effectively and efficiently outside of the organisation.

With data and information as core assets to the industry, companies are finding 30

P h a rm a F o c u s A s i a

ISSUE - 20 2014

that not all information is equal and that the willingness to relinquish control of information varies, depending on where in the organisation the information resides. Ongoing innovation in the commercial IT cloud solution space has recognised these concerns and is developing (and evolving) product offerings for each need.

Key factors surrounding it cloud adoption in the life science industry

Fundamentally, the opportunity for IT cloud solutions is driven by the need to reduce costs while maintaining the same, or better, organisation-wide operational performance. While near term ROI is

driving investment today, the shift to IT cloud solutions is also supported by the significant potential for long term benefits for the organisation.

While external, public IT cloud solutions (e.g. Amazon Web Services Elastic Cloud 2) have the potential to reduce IT infrastructure costs by as much as 90 per cent and enable access to increased computational resources on-demand, this approach requires that company data reside outside of the organisation, which potentially exposes the organisation to the risk of accidental, or malicious data access by external parties.

For efforts critical to the organisation (e.g. clinical trials or M&A), the risk of uncontrolled access, no matter how

CoverStory

information technology

The life science industry is becoming increasingly global, in part due to outsourcing to lower cost regions, but also due to growing opportunities in emerging markets.

small, is typically too great to accept, and in these situations, the status quo, or better controlled options (e.g. internal IT clouds) are likely to remain the norm for the foreseeable future.

It is also clear that the industry is undergoing transformational change in a number of areas that are relevant to the discussion. The life science industry is becoming increasingly global, in part due to outsourcing to lower cost regions, but also due to growing opportunities in emerging markets. At the same time, M&A is increasingly becoming the near term path to backfilling anticipated revenue losses from blockbuster patent expirations, requiring organisations to regularly integrate and

Alan S Louie Research Director IDC Health Insights USA

www.pharmafocusasia.com

31

information technology

manage new assets and capabilities as they seek to build for the long term.

This constant change would challenge the IT strategy and infrastructure of any organisation, but comes at an especially difficult time as the industry seeks rapid change while needing to maintain tight regulatory control to avoid compliance issues and potential penalties.

Additional pressures on IT are arising from the geometric growth in the amounts of data that are being generated by life science research. While most of the data is being generated during discovery research, data in clinical development is also growing (particularly from imaging and genomics), as is the data supporting M&A activities.

Effective management of these growing data and information requirements will be key to organisational success over the long term.

Who, When and Where

A critical mistake for cloud vendors focused on the life science industry would be to assume a (one size fits all) approach to the adoption of IT cloud solutions. Information within the industry can be heavily siloed, often by design, and management of different data often carries regulatory compliance requirements that also bear financial risks. In looking at the way that data and information are managed in the industry, one needs to focus on the key industry segments as key differentiators as to how much control organisations are willing to relinquish in pursuit of direct cost savings and improved operational effectiveness.

Key areas and their segment-specific requirements include: Discovery research: This early part of the life science value chain is largely unregulated, highly diverse, and multifaceted in its generation of and use of data and information. New innovations and technology advances are increasingly automating the generation of large quantities of data and it is not uncommon to need to create and manage terabytes of data on a routine basis. The 32

P h a rm a F o c u s A s i a

ISSUE - 20 2014

With the regulated nature of the data also comes a financial penalty for non-compliance as well as the potentially more devastating risk of damage to the industry's high standards for ethics and value to humanity.

very large datasets are often unstructured and the underlying purpose and design of the research that generated the data is typically not associated with the data directly. As a result, the risk to the organisation form accidental access or release of discovery research data is relatively low. In discussions with major life science companies, it is clear that this area is a prime opportunity for external IT cloud services.

Key to the value delivered to discovery research efforts includes paying for only what you need from both storage and computing perspectives, the ability to access increased capacity on-demand, not paying for excess capabilities and significant reduction in IT infrastructure capital and operating expenses over time.

Clinical Development: Data generated and used in the management of clinical trials is tightly regulated and core to the ability of an organisation to successfully advance a new drug to market.

Clinical development efforts routinely involve human patients, introducing additional issues and concerns over drug safety in addition to the fundamental issues over whether a drug works or not. While the diversity of data types used in the course of a clinical trial is

much more limited than data generated during discovery research, additional complexity is introduced by the global nature of the clinical development effort, often requiring hundreds of trial principal investigators located in as many locations around the world.

Timely access to information is critical even as companies work to tightly control the collection, transmission, and analysis of the data. With the regulated nature of the data also comes a financial penalty for non-compliance as well as the potentially more devastating risk of damage to the industry's high standards for ethics and value to humanity. As a result, external IT cloud services are not perceived as appropriate for this segment and alternatives, both private IT clouds and vendor-based private cloud approaches (i.e. hosted applications and software-as-a-service [SaaS] are likely to remain the key approaches to data and information management in this space over the long term.

Drug safety: Although primarily an effort under the umbrella of clinical development, drug safety is a key area that merits separate consideration.

Individual drug safety issues are defined as ‘adverse events’ in the industry and severe adverse events (SAEs, including death or other major life threatening impacts) have specific regulatory requirements that companies must meet to maintain regulatory compliance. In particular, SAEs must typically be reported to regulatory agencies within 10 days or severe penalties may result. This issue becomes more complicated as clinical trials are conducted globally, since multiple jurisdictions become involved. The critical nature of safety data, combined with the regulated nature of the clinical trials suggest that cost savings and general operational efficiency improvements are likely to be secondary to meeting regulatory requirements. That said, drug safety is increasingly being looked at as a non-core competency within life science companies and is increasingly being outsourced to qualified application

information technology

vendors (i.e. general contract research organisations [CROs] or specialty drug safety service providers) along with their private IT infrastructures [i.e. private IT clouds].

M&A: Mergers and acquisitions, along with other collaborative efforts, is a growing effort within the life science industry. Partnerships of all kinds are changing the way that organisations manage and share data, requiring new thinking regarding how data is held and used. For traditional M&A, data security and control are paramount, since any lapses can result in lost opportunity. In these cases, the high risk necessitates the tightest control over data and information and, in some cases; companies are only now shifting away from paper, human couriers, and face-to-face signoffs.

Access across corporate firewalls is tightly managed and IT clouds are unlikely to deliver sufficient value to drive change in this space over the foreseeable future.

Broader partnership and collaborative efforts, on the other hand, are also growing (e.g. academic collaborations, precompetitive consortia, and translational research efforts) and to a large extent are being driven by data and information sharing. In these cases, it becomes possible to exploit both external and internal IT cloud solutions as separate, isolated IT ecosystems where key information is available and accessible only to collaborators, separate from other corporate data.

Companies today are actively seeking to consolidate data on an organisation-wide basis as part of ongoing efforts to apply business intelligence to both scientific and business management. Almost by default, these efforts are running into concurrent efforts to apply IT cloud solutions to improve operational efficiency at the operational level. The diversity and scope of implemented IT cloud solutions is likely to complicate these data consolidation efforts. Regardless of the specific approaches selected, it will be critical for organisations to incorporate IT clouds into an overall, organisation-

wide data management strategy, based on the additional complexity that is likely to be introduced from increased dependence on external partners for IT infrastructure.

Where we are going

The life science industry is clearly in the midst of transformational change and it is reasonable to expect that IT will be a core element in the change process.

The industry overall is finally reali sing that it is not significantly different from other major industries in many ways and, as a result, realising that it could benefit from best practices proven in other industries. As an example, the financial industry regularly addresses data security and privacy concerns and M&A issues are regularly addressed by industry in general. It can be expected that IT infrastructure in the life science industry is likely to become increasingly commoditised over the near term, with particular industry segments seeing early adoption as companies look to gain near term cost savings and improved operational effectiveness. Risk and perceived risk can be expected to slow the adoption of IT cloud innovations in other industry segments, with limited or no progress in specific areas where cost concerns are secondary.

Access across corporate firewalls is tightly managed and IT clouds are unlikely to deliver sufficient value to drive change in this space over the foreseeable future.

Globalisation, geometric data growth, and increasingly complex partnering relationships are major challenges that will require changes in the life science industry IT landscape. As companies expand to emerging regions, they are increasingly finding that existing IT infrastructure is inadequate to do science and conduct business effectively.

This shortcoming, while transient, can slow progress at a time when the industry can least afford it. Continuing rapid growth in the generation of data of all kinds is increasingly limited by our ability to digest and extract meaningful insights and is continually complicated by islands of diverse data silos. And finally, the promises of partnering to more efficiently advance pre-competitive research, reduce the overall risk in advancing new drugs to market, and improve patient outcomes over the near term will all require new ways of sharing data and insights that were historically discouraged, requiring new mindsets and social change as organisations seek to work smarter, faster and more efficiently.

While only a single component in broader efforts to advance information management, IT cloud solutions have arrived at a time when they can be effectively leveraged into both short term solutions and long term strategic planning. While taking the jump into IT clouds can be easy, fast, and cheap, it will be important for both senior management and IT administrators to take a step back and reflect on the larger picture to ensure that their efforts are consistent with long term goals and expectations. The life science industry is large, complex, and ripe for opportunity for those companies willing to properly think through their near and long term goals for information management. It is clear that information is, and always has been, key to success and a broader information management strategy that includes IT cloud solutions is likely to be important as both an enabler in the near term and a requirement over the long term. www.pharmafocusasia.com

33

CHINA-PHARM 2014

Your gateway to China market

The 19th China International Pharmaceutical Industry Exhibition (CHINA-PHARM 2014) will be held at Shenzhen Convention & Exhibition Center on October 28-31, 2014. CHINA-PHARM is jointly organised

by China Center for Food and Drug International Exchange and Messe DĂźsseldorf (Shanghai) Co., Ltd. After 18 editions held in Beijing and Shanghai alternatively over the past few years, CHINA-PHARM will be the first time to be held in Shenzhen which is in south China. It will continue to serve as a platform for exchanging latest information in the sectors of pharmaceuticals, food and cosmetics.

The exhibition area of CHINA-PHARM 2014 will be 30,000s.q.m. It’s expected that over 500 renowned domestic and foreign businesses will bring their

34

P h a rm a F o c u s A s i A a

ISSUE - 20 2014

innovative solutions and equipments onsite, attracting 25,000 person-times of trade visitors. Approximately 15 per cent of visitors are expected to be from overseas. The recruitment of exhibitors is underway. Since the start of recruitment of regular customers, around 60 per cent of booths have been booked.

International forums on pharmaceuticals, cosmetics and food to be held concurrently to interpret policies and regulations Concurrent events of the past exhibitions provided an opportunity of exhibitors and trade visitors to exchange their ideas on policies, targets and expertise. Besides ISPE-CCFDIE China Conference Series Events, CHINA PEPMAK, CHINA COSMAK and CHINA

FOODMAK will be held concurrently during CHINAPHARM 2014. Leaders from relevant authorities and top experts from well-known enterprises and associations will exchange views and discuss hot topics through interpretation of policies, laws and regulations, keynote speeches, case studies, seminars, exhibitions and forums.

ISPE-CCFDIE China Conference Series Events, concurrently held with CHINA-PHARM since 2012, has grown as the most famous and professional conference on pharmaceutical engineering in China.

As an annual-held international conference, ISPECCFDIE China Conference Series Conference has been focused and appraised by industry players with an increase in its level and number of participants. During ISPE-CCFDIE China Conference Series Events 2014, the Drug Certification Center of China Food and Drug Administration will become an official organiser. The Center will implement and improve China’s newly-revised GMP, enhance communications between the government and the non-governmental sector, and improve the overall quality of GMP inspectors to enhance the capacity of China’s pharmaceutical sector and ensure the safety of medication for the public.

In 2013, we witnessed adjustments in China’s pharmaceutical sector. Since China Food and Drug Administration was set up, its supervision function on food and cosmetics (exclusive of pharmaceuti-

cals) has been adjusted. Safety supervision on pharmaceuticals, food and cosmetics is positioned with new requirements and orientations. China Center for Pharmaceutical International Exchange, one of the organisers of CHINA-PHARM, was renamed as China Center for Food and Drug International Exchange.

Facing new opportunities and challenges, CHINAPHARM invites customers and industry players to meet together in Shenzhen. CHINA-PHARM will continue to contribute to implementing GMP in China, upgrading technological installation for manufacturers, introducing advanced equipment and technology and helping Chinese pharmaceutical equipment enterprises catch up with peers overseas.

The organisers of CHINA-PHARM organised China’s leading Pharmaceutical Machinery Pavilion for Interpack 2014 – the world No.1 packaging and process show. All the exhibitors of China’s leading Pharmaceutical Machinery Pavilion are the exhibitors of CHINA-PHARM. They showcased the advanced pharmaceutical machineries, technologies and creative solutions from China. During Interpack, the organisers also held a presentation named CHINA DAY, focusing the updated policies and information of drug, food, cosmetic Industry in China and the highlights and future development of CHINA-PHARM. Visit the official website www.china-pharm.net to obtain in-depth information, and to be part of the industry feast!

Advertorial www.pharmafocusasia.com

35

Peptides Remain a Growth Story

Bachem’s strategic refocus

36

P h a rm a F o c u s A s i a

ISSUE - 20 2014

1. How has peptide business evolved at Bachem and what changed over the last 14 years?

Since 1971 we were among the very first to supply peptide chemists around the world with the necessary tools to make peptides and soon had the biggest selection of such amino acid derivatives available from stock. We also began to synthesize many bioactive peptides in the 70s and 80s, which we sold to customers around the world. As peptides became drugs, we metamorphosed from a pure research chemical manufacturer into the best provider of active pharmaceutical peptides in the world.Over the last 14 years, the amount of peptide APIs increased dramatically, as did the standards for purity. There is also a high demand for longer and more complex structures. We still are at the forefront of the field.

José de Chastonay, Chief Marketing Officer Bachem Group, Switzerland José de Chastonay joined Bachem AG in 1991 as International Marketing Manager. As of 1992, he relocated to the USA, first as President and COO of Bachem Bioscience, Inc., and subsequently of Bachem, Inc. and ultimately as President of Bachem Americas. In 2007, he left Bachem to become CEO of Irvine Scientific Inc. and Managing Director of Wombat Capital Ltd. in Los Angeles, before rejoining Bachem as Chief Marketing Officer in 2012. José de Chastonay started his industrial career with Ares Serono as Assistant Director of Biotechnology and joined Roche Diagnostica as International Product Lines Manager several years later. He served on the Board of Directors of Viroblock SA as well as on the Strategic Advisory Board of Rapid Pharmaceuticals and serves as Treasurer of the European University Foundation. José de Chastonay earned his Ph.D. in medical microbiology from the University of Bern and his MBA from the European University in Montreux.

2. In 2012 Bachem has taken the strategic decision to re-focus on the core business of peptides. Why was this decision made? How has it benefitted Bachem in the last two years?

Bachem’s re-focus on peptides is the result of an in-depth analysis of the market. We are convinced that peptides remain a growth story. In order to stay ahead in the field, Bachem must fully concentrate its resources on the core business.

It’s a clear strategy to constantly build upon our pole position and grow in existing and new markets. We benefit from our re-focus by achieving strong growth in the New Chemical Entities (NCEs) business, where we are recognized as a reliable business partner with innovative drive, who can ensure the successful execution of peptide projects and deliver superior quality solutions.

3. What are your views on the market for peptides?

We expect that in Asia, especially in China, the pharmaceutical industry will grow rapidly and therefore we consider the region as an increasing market for peptide drugs. Bachem is getting ready to enter these markets competitively, because there should be an increased need for peptide solutions there. It would be difficult to stay ahead of our competition if we did not capitalize on growth opportunities in emerging markets. Also the future will belong to those CMOs that can build successful partnerships with customers around the globe. The market is highly regulated, so product quality as well as compliance are essential attributes to success.

4. What are the key challenges in the market today that Bachem looking to solve by focusing on peptides?

The CMO business in the pharmaceutical industry is highly competitive and one of the key developmentsis that many APIs are now manufactured in Asia. By focusing on peptides we are well prepared to maintain our leading position. For years we have established best industry practice in the execution of peptide projects for our customers. Our facilities, equipment and approach to manage product development as well as scale up contribute to staying cost competitive. Distractions in adjacent fields would break the crucial focus.

5. The primary objective of Bachem vision is to be the undisputed leader in peptides. With this in mind, what do you think is on offer this year?

Bachem will continue to evolve the peptide field. One hot topic is the targeted synthesis of specifically glycosylated proteins and peptides. We developed an industrial scale process for Interferon beta-1a with our Japanese partner GlyTech Inc. last year. Such products have interesting properties and can now be made economically on an industrial scale.We hope to catalyze the finding of potential new drug compounds in the form of glycopeptides.

6. How important do you think is it to have a local journal giving the Asian perspective on developments in the pharmaceutical world, and at the same time, to keep readers informed about what is happening in other parts of the world and markets that they might be considering targeting?

The Asian pharmaceutical industry with its rapid growth already is an important part of the business. People and companies need to be well aware of what is going on in the industry on a global level. I am personally convinced, that a local Asian journal will contribute to an open-minded environment and facilitate cross cultural understanding. This may be a key for future innovation and development within our industry, because global partnerships and cooperations may become increasingly important to reach the ultimate goal of creating innovative drugs in the future.

www.pharmafocusasia.com

37

PharmaLytica

Breakthrough opportunity for India bio-pharma sector

India is set to emerge as a leading player in the global biotech arena. According to Ernst & Young reports, global biotech companies will have to deploy significant time and resources for reimbursement and managing payer expectations. And there would be constraints that the global biotech players may face, driving them to look at more optimal avenues.

On the other hand, India’s strengthening commitment towards the healthcare sector in general and Government of India playing a major supporting role by creating suitable physical, financial, legislative and regulatory infrastructure in particular, has opened up interesting opportunities for Indian BioPharma players to venture and capitalize upon.

38

P h a rm a F o c u s A s i A a

ISSUE - 20 2014

The Indian BioPharma market–comprising primarily of vaccines, therapeutic drugs, insulin, animal biologicals, stations and diagnostics, continues to grab the largest share of the total biotech industry revenue. However, India needs to look at human resources in the biotech / biopharma field, as a priority, and needs to put in order and strengthen India’s biotech / biopharma regulatory agencies, systems and mechanisms. Growing at an average of 20 per cent year-on-year may turn out to be a dream if required action is not taken at the right time.

UBM India the organiser of CPhI & P-MEC, South Asia’s biggest and most comprehensive Pharma event proudly announcing the launch of our second

www.pharmafocusasia.com

39

Pharma event in India viz. PharmaLytica with active support from Karnataka Drugs and Pharmaceuticals Manufacturers Association (KDPMA) - a trade show and conference, to be held from 25th – 27th September, 2014 at the Bangalore International Exhibition Centre (BIEC), Bangalore, India.

The Indian BioPharma industry – comprised of a large pool of scientific talent, world class information technology and rapidly growing pharmaceutical sector and looking lucrative – is still at its nascent stage with less heavy regulation. There need to be a single platform to not only exchange ideas and harness opportunities but also get associated with industry experts and their knowledge.

PharmaLytica 2014 seeks to channelize inputs from the chief executives of biotech, IT, pharma & analytical instrument companies, custom manufacturing, Contract Research Organisations (CROs), venture capitalists, policy makers, academicians, universities and Research & Development (R&D) organizations to harness the immense potential of the industry into a working reality. This will add value to the interest seekers’ who are designing their strategies to venture into the science-clad ocean and gearing up to discover the underneath hidden opportunity.

PharmaLytica integrates UBM’s expertise and understanding of Pharmaceuticals, BioServices, Analytical & Lab Services with the limitless possibilities in the Pharma Industries and presents it as one solid B2B package.

PharmaLytica is the combination of a trade fair and conference where participants can pick up on the latest industry trends, techniques and methods. It connects pharmaceutical community with

Bangalore-India’s new BioPharma hub The Indian biotech sector has generated revenues of US$2.5 billion and is growing at an annual rate of about 35 per cent. The industry today comprises 340 core biotech companies in 5 distinct segments, namely biopharma, bioagriculture, bioinformatics, bioindustrial, and bioservices. Karnataka alone has over 180 biotech companies in India and these facts reinforce our decision to hold PharmaLytica event at BIEC, Bengaluru, India from 25-27 September 2014.

outsourcing solution providers, including clinical trials, contract research, custom manufacturing, biotech, IT, analytical services among others from across India and select global markets.

For more details you can get in touch with Mr. Rahul Deshpande T: +91 22 61727165 | M: +91 98209 02476 or E: rahul.deshpande@ubm.com

Advertorial 40

P h a rm a F o c u s A s i A a

ISSUE - 20 2014

Industry Reports CHRONIC HEART FAILURE – GLOBAL DRUG FORECAST AND MARKET ANALYSIS TO 2022

A report by Global Data Executive Summary This table provides a summary of the key metrics for chronic heart failure (CHF) in the seven major pharmaceutical markets during the forecast period from 2012–2022.

Sales for Chronic Heart Failure by Region 2012–2022 GlobalData estimates that sales of CHF therapeutics in 2012, the base year of the forecast period, totalled approximately $2.56 billion in the seven major markets (7MM): US, France, Germany, Italy, Spain, UK, and Japan. Branded drugs alone accounted for only $1.02 billion across the markets, while generics made up the majority of sales. As a result of higher drug prices and a large CHF population, the US dominated the 2012 base-year sales, with 51% of the overall market, totalling approximately $1.30 billion in sales. The CHF market has been slowly overtaken by generic drugs, and more branded products are expected to lose market exclusivity during the next few years.

By the end of the forecast period in 2022, CHF sales will grow to $4.45 billion at a Compound Annual Growth Rate (CAGR) of 5.7%, as shown in the figure below

www.pharmafocusasia.com

41

Industry Reports The major drivers of CHF market growth over the forecast period are: • The launch of Novartis’ novel combination drug LCZ-696 in 2015 will mark the first entrance of a novel branded CHF drug in the past five years, boosting the overall market size considerably during the forecast period.

• The prescription of mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is expected to increase across the CHF markets within this report’s 10-year forecast period.

The major barriers that will restrict the growth of the CHF market during the forecast period are: • A significant barrier faced by the CHF market is the lack of late-stage pipeline drugs.

• Patent expirations of most of the drugs marketed for CHF have resulted in a market that is crowded with generics; the presence of inexpensive generics will diminish the overall value of the market and may hamper the uptake of LCZ-696.

The table below represents the drivers and barriers in the global CHF market during the forecast period.

Drug Developers Frequently Pursue Approval in Hypertension Prior to Seeking a Label Expansion into Chronic Heart Failure In recent years, pharmaceutical companies have entered the CHF market only after gaining initial approval of their drugs in hypertension (high blood pressure). While obtaining approval in CHF has not been an afterthought, it has been sought by companies to expand their products’ lifecycles, rather than serving as a leading aspect of their market entry strategies. Novartis’ LCZ-696 will follow in the footsteps of its predecessors by first filing for hypertension

42

P h a rm a F o c u s A s i a

ISSUE - 20 2014

in 2013, followed by CHF in 2014. However, the similarity ends there. Unlike the currently marketed CHF drugs, LCZ-696 targets the underserved segment of the population with heart failure with preserved ejection fraction (HF-PEF); to date, no drug developer has successfully targeted this population. Furthermore, it is a first-in-class combination drug, whereas the majority of CHF therapies fall into wellestablished drug classes.

The CHF therapy market has been fairly stagnant for a number of years, and is marked by the presence of generics.

However, LCZ-696’s launch is poised to mark the beginning of a new era in which companies will be pursuing truly novel approaches for treating CHF. These approaches include potentially game-changing nonpharmacological therapeutic approaches. For example, Celladon is developing the gene therapy Mydicar (rAAV1-SERCA2), while Bioheart and Cardio3 BioSciences are developing stem cell therapies. In addition, other companies, including Bayer and Cytokinetics, both aim to break into the CHF market with novel drugs, in keeping with the trend started by Novartis.

The Chronic Heart Failure Market Has Considerable Unmet Needs, Despite the Availability of Well-Established Treatments Although the CHF market has numerous well established therapies, it is marked by the presence of a number of unmet needs in current treatments. All of the standard CHF therapies are easily accessible to patients because most treatments are generically available and are inexpensive.

However, these standard therapies cater to the needs of many, but not all, CHF patients.

Industry Reports GlobalData’s research indicates that the overall attainment level of unmet needs in current treatments is within the moderate-to-high range, as shown in the table below.

Of the drugs that are in late stages of development specifically for chronic, rather than acute, heart failure (HF), only Novartis’ LCZ-696 is likely to address a major unmet need in the current treatment paradigm for CHF by providing a treatment for HF-PEF patients. LCZ-696 was tested in HF-PEF in a Phase II trial, with encouraging results. It is currently being evaluated in a Phase III trial in the US, Europe and Asia to investigate its efficacy in patients with New York Heart Association (NYHA) Class II–III heart failure with reduced ejection fraction (HF-REF).

GlobalData expects LCZ-696 to receive Food and Drug Administration (FDA) approval in 2015 for HF-REF and to launch shortly thereafter. At the time of the publication of this report, Novartis had not yet publically disclosed any plans to pursue further development of LCZ-696 in the HF-PEF population. However, given the lack of efficacious treatments and the corresponding high level of unmet need in this population segment, GlobalData expects that Novartis will conduct a Phase III trial in the HF-PEF population. In the event that Novartis pursues the development of LCZ-696 for HF-PEF and confirms its efficacy in this segment of the population, it will be the first drug to be approved for the HF-PEF and will fulfill the unmet need of treating this underserved population.

There remains an opportunity to develop more efficacious treatments that could further increase survival times for CHF patients, particularly in patients who continue to suffer from worsening CHF, despite the use of the existing treatments.

Novel Combination Drug LCZ-696 Will Be a Major Market Player by 2022 Novartis’ LCZ-696, a combination of Diovan (valsartan) and a new agent — a neprilysin inhibitor, AHU-377 — is the only drug forecast to be launched in the next 10 years.

The market entry of this novel combination drug in 2015 will mark the first entrance of a novel branded CHF drug in the past five years, boosting the overall market size considerably during the forecast period. LCZ-696 has the potential to replace angiotensin-converting enzyme (ACE) inhibitors in the treatment paradigm for CHF. In addition, LCZ-696 will also steal patient share from Diovan and other angiotensin receptor blockers (ARBs), which are given to patients who cannot tolerate ACE inhibitors.

GlobalData forecasts that LCZ-696 will achieve sales of approximately $1.87 billion by 2022, the final year of the forecast period.

Market Opportunities for New Entrants

What Do the Physicians Think?

Although the CHF market has several efficacious treatments for HF-REF patients, there is a lack of efficacious therapies that can reduce morbidity and mortality in this population segment. To date, no drug has demonstrated sufficient efficacy in terms of reducing morbidity and mortality in HF-PEF in large-scale clinical trials. Therefore, this unmet need presents a significant opportunity for investment by drug developers. Novartis’ LCZ-696 is the only drug that has shown some promise in treating the HF-PEF population. In addition to the development of LCZ-696, a large-scale trial sponsored by the US National Institutes of Health (NIH) is currently underway for the treatment HFPEF using the well-established MRA, spironolactone. The much-awaited results of this trial are expected in June 2013, and will shed more light on the possible role of MRAs in the HF-PEF population.

Physician experts interviewed by GlobalData acknowledged that LCZ-696 could change the treatment paradigm for CHF if it shows significantly superior efficacy to ACE inhibitors in its ongoing trials. However, if LCZ-696 shows similar efficacy to ACE inhibitors, it is unlikely to have a significant impact on the CHF market. Although Phase II trials of LCZ-696 did not raise any safety concerns, one physician pointed out the risk of heightened adverse effects due to its dual action.

There is a significant need for CHF treatments that are safe to use in the presence of comorbidities such as renal impairment, anemia, arthritis, chronic obstructive pulmonary disease (COPD) and asthma. Due to the high prevalence of

44

multiple comorbidities in the elderly population, physicians often face difficulties in treating these patients because many of the CHF drugs are contraindicated in them because of these comorbidities.

P h a rm a F o c u s A s i a

ISSUE - 20 2014

“The objective of the currently-running trial [for LCZ-696] is to see whether we can replace ACE inhibitors, which is one of the pillars, one of those foundations, of the pharmacological treatment of heart failure. That trial is a headto-head trial of LCZ-696 versus the gold-standard ACE inhibitor treatment [enalapri]. So, if LCZ-696 were to be significantly superior to enalapril, then it would potentially replace ACE inhibitors and other key drugs [ARBs, MRAs, beta blockers]. So, absolutely, yes, of course, it could be at a very important position in the guideline. It could be right at the top where you start.”

“I am skeptical about the dual blockade because dual blockade in the RAAS [renin-angiotensinaldosterone] system does not really have convincing data. If you combine drugs that may induce hypotension, it may not be beneficial; in fact, it may be risky for the patients. So, the ongoing trial results need to show that this combination will provide benefit for the patient.”

which one we use first. But because the trials for ACE inhibitors were done first, and those with beta blockers later, the convention is you start someone who comes in untreated with an ACE inhibitor for [a] few weeks, build up the dose to a middle region, and then start a beta blocker and then up-titrate it.”

Key opinion leader, January 2013 Key opinion leader, January 2013 As indicated in the published treatment guidelines, all interviewed key opinion leaders (KOLs) agree that ACE inhibitors and beta blockers are the current standard care of therapy in CHF, and are likely to remain so during the next 10 years.

“According to the guidelines, everyone should be started with an ACE inhibitor and a beta blocker. The order is usually…to start with an ACE, reach a reasonable dose, then start a beta blocker and uptitrate. The order of this — which one to use first — is debated. A couple of trials looked at it and said it is clear now that it doesn’t matter

Interviewed KOLs also indicated that MRAs are used more frequently in Europe than in the US for CHF treatment, and they anticipate that the use of MRAs will increase in the US and Japan during the forecast period.

“Mineralocorticoid receptor antagonists, even in 2012, are used much less in the US and Canada than they are in Europe and Latin America. That is because among some physicians, they have a bad reputation in the US and Canada, in terms of safety. Whereas in Eastern, Central, and Southern Europe, physicians use mineralocorticoid receptor antagonists very widely and very happily.”

Key opinion leader, January 2013

“autoclaves are our business”

Laboratory autoclaves delivering the ultimate in steam sterilising performance and reliability multiple installation of rectangular and cylindrical chamber Priorclaves

• Choice of more than 60 standard autoclaves • Small benchtop and high capacity free-standing designs • Standard ranges up to 700L • Special designs more than 7,500 litres capacity • Choice of top or front loading models • Antimicrobial finish • Noted for small footprint and high capacity • Low loading heights • World-wide recognition for build quality

call +44 (0)20 8316 6620 email sales@priorclave.co.uk visit www.priorclave.co.uk

double-door Priorclaves

small-footprint, free-standing Priorclaves

www.pharmafocusasia.com

45

Industry Reports TYPE 2 DIABETES - GLOBAL DRUG FORECAST AND MARKET ANALYSIS TO 2022 – EVENT-DRIVEN UPDATE A report by Global Data Executive Summary Sales for Type 2 Diabetes by Region 2012–2022 This report focuses on type 2 diabetes pharmaceuticals in seven major markets (US, France, Germany, Italy, Spain, UK, and Japan) and three emerging markets (China, India and Brazil). These 10 markets will be referred to as the global market.

The global type 2 diabetes pharmaceutical market in the 2012 base year was $28.1 billion, including both branded and generic drugs. Branded products alone accounted for $19.2 billion across the 10 markets. At 58% of the overall type 2 diabetes market, the US is clearly the dominant market, totaling $16.4 billion in branded and generic pharmaceutical sales. This is due to the much higher prices of pharmaceuticals in this country and due to the high diagnosed prevalence. The next-largest individual market is Japan, at 9% of the worldwide type 2 diabetes market, totaling $2.5 billion. The 5EU countries make up 18%, while emerging markets, including India, China and Brazil together, account for 15% of the total market.

Over the forecast period, emerging markets will grow in size most rapidly, due to a dramatic increase in the prevalence and diagnosis of type 2 diabetes, which are attributed to increased life expectancy and lifestyle changes that have occurred through rapid economic growth. Uptake of branded drugs will also increase in these markets due to fast growth of the middle class. Sales in the US will grow by about 9% per year over the forecast period. The European and Japanese markets will also increase steadily; however, cost constraints in Europe and the slow regulatory process in Japan will slightly limit growth in these regions.

The table below presents the drivers and barriers in the global type 2 diabetes market during the forecast period.

The figure below illustrates the global type 2 diabetes sales for the seven major markets (US,

46

P h a rm a F o c u s A s i a

ISSUE - 20 2014

Sanofi is developing a superior version of its own product Lantus and also a fixed-dose combination of Lantus and Lyxumia in order to protect its own franchise. Sanofi is also stepping up its biosimilar insulin development program and expects to have two projects in clinical development soon, which are likely to be versions of Eli Lilly's Humalog and Novo Nordisk's Novolog. Only Novo Nordisk does not have a biosimilar insulin strategy, which reflects its existing portfolio of novel insulin analogs in development.

Future leaders during the forecast period will include Novo Nordisk, AstraZeneca, Merck, Eli Lilly/Boehringer Ingelheim, Takeda, and Johnson & Johnson. All of these companies have late-stage pipeline products or very recently marketed products that have the potential to strengthen significantly the companies’ current portfolios. Novo Nordisk will remain the market leader in the type 2 diabetes market 5EU, and Japan) and three emerging markets (China, India and Brazil) during the forecast period. China will increase its global market share from 9% to 14%, stealing market share predominantly from the 5EU and Japan, which will lose 4% and 3%, respectively.

Corporate Shift in Focus from Therapeutic Value Towards Competitive Pricing Historic leaders in the type 2 diabetes space include Novo Nordisk, Bristol-Myers Squibb, Sanofi, Novartis, GlaxoSmithKline, Merck, Eli Lilly and Takeda; AstraZeneca and Boehringer Ingelheim have recently entered the space through the formation of partnerships. All of these companies have had or will have blockbuster drugs in this space.

Takeda and GlaxoSmithKline faced a large patent cliff in 2012 with the loss of market exclusivity for their blockbuster drugs, Actos and Avandia, respectively. Avandia’s patient share dropped sharply even before the patent cliff due to its adverse effects. Takeda is compensating for Actos’ loss of patent protection by strengthening its diabetes portfolio through partnerships, but also by developing some novel, first-in-class molecules.

Novo Nordisk, Sanofi and Eli Lilly are all facing patent expiry for their blockbuster insulin analogs (Novolog, Lantus and Humalog, respectively) this and next yearin 2013 and 2014, and will suffer erosion to biosimilars from around 2015, when presumably all the regulations for biosimilar insulin production will be in place. The companies are undertaking different strategies, whereby they either go on the offense or defense, to address this problem. Eli Lilly already has a Lantus biosimilar in late-stage development, which will be a strong competitor to Sanofi’s Lantus, while

US

SEU

Japan

China

India

Brazil

US

SEU

Japan

China

India

Brazil

www.pharmafocusasia.com

47

Industry Reports overall, and particularly in the insulin market, with its several insulin analogs, marketed or in development, and its current blockbuster from the GLP-1 class, Victoza. AstraZeneca will be the fastest growing company in the type 2 diabetes space and may become the second-largest player with its two potential blockbusters: first-to-market (in the EU and China) SGLT-2 inhibitor Forxiga, and first-to-market once weekly GLP-1 agonist Bydureon. AstraZeneca has the potential to run shoulder to shoulder with Merck, which will continue capitalizing on its blockbuster Januvia throughout the forecast period.

The type 2 diabetes market is very mature, marked by a late-stage pipeline filled with me-too drugs. Some companies, such as Sanofi, have started focusing on price rather than on therapeutic value. Sanofi’s recently marketed drug Lyxumia was launched at a heavy discount to its rival GLP-1 agonists, BMS’ Byetta and Novo Nordisk's Victoza.

Lyxumia is the fourth-to-market GLP-1 product with low level of differentiation in the GLP-1 space, and thus Sanofi had to offer a competitive price in order to win market share.

With health systems in many markets facing cost pressures today, this is likely a strategy that other companies will adopt with their me-too drugs that are in late-stage development.

However, some companies, like Eli Lilly, are embracing a new business model, discarding the traditional blockbuster

appraoach and instead focusing on highly individualized solutions for patients.

The figure below provides an analysis of the company portfolio gap in type 2 diabetes for the forecast period.

Current Therapies Leave Unmet Needs in Type 2 Diabetes Market The type 2 diabetes therapeutics market is crowded with many generics and branded generic drug products, comprising several classes of treatment options. Nevertheless, owing to the increasing prevalence and progressive nature of the disease, there are considerably high unmet needs within the indication. Overall, these unmet clinical needs are interrelated and they include improved durability of treatment, a better balance of efficacy of glycemic control with cardiovascular safety, hypoglycemia avoidance, and tolerability and ease of compliance.

The table below lists the prominent unmet needs in the type 2 diabetes market, along with a numerical value to depict the level of attainment of these needs in different markets (1 = low attainment, 5 = high attainment). The table also ranks the relative importance of each of the unmet needs on a scale of low, moderate, or high.

Entry Opportunities for Type 2 Diabetes Market Access All currently available treatments for type 2 diabetes are initially effective and reduce complication rates, but they lack the ability to maintain glycemic control in the long term because of the progressive nature of pancreatic -cell

48

P h a rm a F o c u s A s i a

ISSUE - 20 2014

dysfunction; this represents one of the highest unmet needs in the type 2 diabetes space. As the late-stage pipeline is dominated by me-too drugs and by drugs belonging to novel classes that are not very different from the marketed classes, most of the unmet needs will remain unfulfilled in the foreseeable future. Therefore, this market has a significant growth opportunity for new patent protected products.

Molecules in the earlier stages of development, Phase II or earlier, employ various novel mechanisms of action. These early-stage drug classes include 11-beta-hydroxysteroid dehydrogenase (11b-HSD) type 1 inhibitors, G proteincoupled receptor 119 (GPR119) agonists, glucokinase activators, ranolazine, fructose-1,6- bisphosphatase inhibitors, protein tyrosine phosphatase 1B inhibitors, carnitine palmitoyltransferase 1 inhibitors, acetyl CoA carboxylase 1 & 2 inhibitors, salicylate derivatives, and a number of other novel agents that may hold promise for fulfilling some of the unmet needs in type 2 diabetes. In order to address the biggest unmet need in type 2 diabetes, new drugs must address the problem of insulin resistance, as this is the root of the disease, but they must do this while offering a strong cardiovascular safety profile and not causing weight gain, which is currently the biggest problem with insulin sensitizers such as TZDs.

DPP-4 Inhibitors and GLP-1 Receptor Agonists Will Still Dominate the Market in 2022

weekly instead of once daily administration. This advantage will not give them as much of an edge as it would in the injectable GLP-1 space, as DPP-4 inhibitors are oral drugs.

Merck’s MK-3102 will achieve sales of $591m by 2022. One distinguished and quite unique feature of the type 2 diabetes market, illustrative of the rapid growth expected in this disease area, is its ability to support multiple key growth drivers in single drug classes, and therefore all of the upcoming me-too drugs will gain certain share of this huge market, particularly with the novel ADA/EASD treatment guidelines which push for patient-tailored approaches.

The only first-in-class drug in late-stage development (in preparation for Phase III trials), Eli Lilly’s LY2409021 (glucagon receptor antagonist), will achieve great success.

Until January 2014, there was an additional first-in-class drug in late stage development, Takeda’s fasiglifam; however, the company terminated its trial due to concerns with liver safety, leaving the global type 2 diabetes Phase III pipeline completely void of any first-inclass molecules. Therefore, Eli Lilly’s LY2409021 may be the only drug with a novel mechanism of action to reach the type 2 diabetes market within the next five years. This drug does not address the crucial issue of insulin resistance, but it employs a novel mechanism of action and could be used as an add-on therapy. LY2409021 will likely reach sales of over $1 billion by 2022. Another first-inclass drug in the late stage, Roche’s

During the 10-year forecast period, we anticipate that the type 2 diabetes market will not experience a fundamental shift in the classes of drugs that are preferred by physicians. Rapid uptake of drugs from the novel class of SGLT-2 inhibitors will occur; however, DPP-4 inhibitors and GLP-1 receptor agonists will continue dominating the noninsulin type 2 diabetes space because SGLT-2 inhibitors will often be used as a third-line treatment. GLP-1 receptor agonists will experience the fastest growth of all classes (CAGR of 13.4%), due to their weight-loss effects and their novel onceweekly administration, which is preferable to the standard once- or twice-daily therapies. Three me-too drugs from the GLP-1 class will reach the market over the forecast period: GSK’s albiglutide, Eli Lilly’s dulaglutide and Novo Nordisk’s semaglutide. They are all once-weekly therapies like BMS’ currently marketed Bydureon, but they have a somewhat better clinical profile in terms of convenience. As albiglutide will reach the market first among these three upcoming agents, it will gain a significant market share and achieve sales of $1.2 billion by 2022. Upcoming DPP-4 inhibitors, such as Merck’s MK-102 and Takeda’s trelagliptin, will also only offer an advantage in terms of convenience, with once-

www.pharmafocusasia.com

49

Industry Reports aleglitazar (dual PPAR agonist), has also been retracted very recently from its Phase III trials, which will alter the future of the type 2 diabetes competitive landscape, leaving more room for other new entrants to gain market share.

The ultra-long-acting insulin analog, Eli Lilly’s insulin peglispro, will also reach sales of almost $1 billion in 2022.

The drug’s clinical profile (long duration of action and efficacy in achieving weight loss) would typically enable it to become a big blockbuster drug; however, it will face stiff competition from another ultra-long-acting insulin analog, Novo Nordisk’s Tresiba, and also from the biosimilars of the currently established long-acting insulin analogs.

What Do the Physicians Think?

“I think that [the number of] people needing a second and third drug is going to increase dramatically in the next 10 years and that we will just see those numbers go up, up, up.

Two things are going to drive that up. One is the expectation that we’ll treat these people fairly aggressively to get their A1c down to around 7 to 7.5. The target appears to be moving based on a few of the studies, but we are not going to tolerate people after 8.5 and 9 like we used to.

That’s going to drive it, and second is that most people are not going to have a control over lifestyle, they are going to continue to overeat and under-exercise and they are going to see their weight continue to go up and therefore their need for more medications will go up with it. So I think [in this] the market, the sky is the limit on how much the market is going to be.”

Key Opinion Leader, April 2013 “I think over the next 10 years the long-acting GLP-1 receptor agonist therapies will increase the most, because now you know the companies will be developing once-aweek treatments… Longeracting preparations, if they are proved to be effective and safe, will be used more and more because they really do have a benefit in weight loss.”

Key Opinion Leader, April 2013 “Weight change direction or level and the risk of hypoglycemia, these are strong determinants for the choice of the drug today or in the future even more.”

Key Opinion Leader, April 2013 “My biggest challenge [with type 2 diabetes] has been the lack of long-term efficacy; that the disease is complicated, the disease is resilient, and most of the agents are not potent enough to get everybody under control long enough. So, lack of efficacy and having therefore to combine

50

P h a rm a F o c u s A s i a

ISSUE - 20 2014

medications has been my biggest challenge.”

Key Opinion Leader, April 2013 “We have SGLT-2 inhibitors, we have the longacting GLP-1 receptor agonists, DPP-4 inhibitors, and this will be quite a choice now for physicians to find the right drugs or right combination of drugs.”

Key Opinion Leader, April 2013 “The SGLT-2s and the dual PPARs are probably going to have a better impact long-term… the things that increase insulin secretion, somewhat are similar to the sulfonylureas, they are going to have hypoglycemic events, or they are going to cause people to gain weight, or they are going to burn the pancreas out… I am much less impressed with them than I am with the SGLT-2s and the dual PPARs.” Key Opinion Leader, April 2013 “The whole concept of individualization of therapy is very important; it is something that we practiced for a long time.

Each patient is different. We have to give quite a combination of drugs to each patient depending on various factors.”

Key Opinion Leader, April 2013 “I think the use of metformin [first-line therapy] will not change. I think it will continue, but the use of sulfonylureas will decline… I think they will be gradually replaced by newer therapies, some available now, some will be available later in the future.”

Key Opinion Leader, April 2013 “The endocrinologist recognized that being overly conservative can hurt the patients, so in other words if you say that there is no long-term data for new drug that can prevent complications, you can’t wait. I am not going to wait for 10 years for randomized controlled trials to show me that injection will dispel. If I know that it prevents complications, I am happy. We are not going to have 300 randomized controlled trials checking all possible combinations because now it’s so many combinations of drugs you could test. So, me and other colleagues, what we have been doing really for years is that we know what works and we know what doesn’t work … we know that we don’t have data but we really need to prescribe certain therapies without data, knowing what the advantages are. I think that the newer guidelines fully acknowledge the reality, that’s what endocrinologists are doing, I think the guidelines didn’t set up anything new, they are just catching up with what physicians are doing already.”

Key Opinion Leader, April 2013

Books

Pharma's Prescription: How the Right Technology Can Save the Pharmaceutical Business Authors: Kamal Biswas Year of Publishing: 2013 No. of Pages: 224 Description: The pharmaceutical industry needs a shot in the arm - and not a moment too soon. The executive suite is mired in a bygone era, a time when extensive, well-funded pharmaceutical R&D produced blockbuster drugs, kept everything in-house and reaped the financial rewards. But that way of working needs to change.

Executives now need to know what the technologists in their companies are doing in order to survive the next decade. Written for those new to industry, as well as for experienced professionals or specialists looking to expand their knowledge, this book is a must-read for business executives and information technologists alike.

Pharma's Prescription bridges the knowledge gap between current business practices and the most valuable technologies today.

Successful Biopharmaceutical Operations: Driving Change (Biohealthcare Publishing Series on Pharma, Biotech and Bioscience: Science, Technology and Business)

The Impact of Regulation on Drug Development (Pharma, Biotech and Bioscience: Science, Technology and Business) Author: Heinz Guenter Hennings

Author: Chris Driscoll

Year of Publishing: 2014

Year of Publishing: 2014

No. of Pages: 250

No. of Pages: 270

Description: The impact of regulation on drug development provides the reader with a basic understanding of the evolution of global regulatory standards relevant to the research and development process of medicinal products and the role regulatory science plays, i.e. the science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of regulated products. This book provides practical guidance on how to obtain such advice efficiently and how it is incorporated in global regulatory planning and strategies.

Description: Successful biopharmaceutical operations provides a practical guide to transforming biopharma companies into industry leaders through a focus on driving change. The industry has a blind spot concerning this kind of work, because successful change management comes from a focus on people, while our technically-minded ranks invariably prefer a technical focus.

This cognitive bias causes us to pick up the tools we like the best and to swing them enthusiastically - whether they are working or not. This book provides new tools, and readers gain an understanding of how biopharma organizations developed into the cultures we see currently.

www.pharmafocusasia.com

51

Books

Collaborative Innovation in Drug Discovery: Strategies for Public and Private Partnerships (Wiley Series on Technologies for the Pharmaceutical Industry) Author: Rathnam Chaguturu, Ferid Murad Year of Publishing: 2014 No. of Pages: 752 Description: Collaborative Innovation in Drug Discovery: Strategies for Public and Private Partnerships provides insight into the potential synergy of basing R&D in academia while leaving drug companies to turn hits into marketable products.

• Gain global perspectives on the benefits and potential issues surrounding collaborative innovation • Discover how industries can come together to prevent another "Pharma Cliff" • Learn how nonprofits are becoming the driving force behind innovation • Read case studies of specific academia-pharma partnerships for real-life examples of successful collaboration • Explore government initiatives that help foster cooperation between industry and academia.

52

P h a rm a F o c u s A s i a

ISSUE - 20 2014

Molecular Diagnostics and Treatment of Pancreatic Cancer: Systems and Network Biology Approaches

Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing

Authors: Asfar Azmi Year of Publishing: 2014 No. of Pages: 458 Description: Molecular Diagnostics and Treatment of Pancreatic Cancer describes the different emerging applications of systems biology and how it is shaping modern pancreatic cancer research. This book begins by introducing the current state of the art knowledge, trends in diagnostics, progress in disease model systems as well as new treatment and palliative care strategies in pancreatic cancer.

Specific sections are dedicated to enlighten the readers to newer discoveries that have emerged from gene expression profiling, proteomics, metabolomics and systems level analyses of pancreatic cancer datasets. First of a kind and novel network strategies to understand oncogenic Kras signaling in pancreatic tumors are presented. The attempts to computationally model and prioritize microRNAs that cause pancreatic cancer resistance are also highlighted.

Authors: Hamid Mollah, Harold Baseman, Mike Long Year of Publishing: 2013 No. of Pages: 416 Description:Risk management is essential for safe and efficient pharmaceutical and biopharmaceutical manufacturing, control, and distribution. With this book as their guide, readers involved in all facets of drug manufacturing have a single, expertly written, and organized resource to guide them through all facets of risk management and analysis. It sets forth a solid foundation in risk management concepts and then explains how these concepts are applied to drug manufacturing.

Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing features contributions from leading international experts in risk management and drug manufacturing.

The Future of Drug Discovery: Who Decides Which Diseases to Treat?

Transforming Big Pharma: Assessing the Strategic Alternatives

Author: Tamas Bartfai, Graham V. Lees

Authors: John Ansell

Year of Publishing: 2013 No. of Pages: 376 Description: The Future of Drug Discovery: Who decides which diseases to treat? provides a timely and detailed look at the efforts of the pharmaceutical industry and how they relate, or should relate, to societal needs. The authors posit that as a result of increasing risk aversion and accelerated savings in research and development, the industry is not developing drugs for increasingly prevalent diseases, such as Alzheimer's disease, untreatable pain, antibiotics and more. This book carefully exposes the gap between the medicines and therapies we need and the current business path. By analyzing the situation and discussing prospects for the next decade, the The Future of Drug Discovery is a timely book for all those who care about the development needs for drugs for disease.

Year of Publishing: 2013 No. of Pages: 265 Description: In Transforming Big Pharma John Ansell addresses critically how strategy works in the pharmaceutical industry. The longstanding dearth of new products has led to a growing shortfall in revenues.

Ansell assesses the wide range of alternative strategies big pharma companies have been pursuing in recent years in attempting to overcome this. He shows that there is sound evidence to expect the recent upturn in the number of new products reaching the market to go on to greater heights. Chapters assess the complex trends in attrition rates, show how rife spectacular sales underestimation in the industry remains, and explain how conventional wisdom on the chances of product profitability also seriously undersells the industry. The surest route to transforming the prospects for big pharma, Ansell contends, is to step up activity in acquiring and developing new products.

Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs Authors: Rodney J. Y. Ho Year of Publishing: 2013 No. of Pages: 744 Description:Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs, Second Edition addresses the pivotal issues relating to translational science, including preclinical and clinical drug development, regulatory science, pharmaco-economics and costeffectiveness considerations. The new edition also provides an update on new proteins and genetic medicines, the translational and integrated sciences that continue to fuel the innovations in medicine, as well as the new areas of therapeutic development including cancer vaccines, stem cell therapeutics, and cell-based therapies.

www.pharmafocusasia.com

53

Products & Services

Company................................................Page No. STRATEGY China Pharm.............................................17, 32 & 33 India Lab Expo........................................................ 41 Priorclave Limited................................................... 43 UBM India Pvt Ltd - CPHI&PMEC............IBC, 10 &11 UBM India Pvt Ltd – PharmaLytica...........36, 37 & 38 RESEARCH & DEVELOPMENT Bachem AG...............................................03, 34 & 35 BOSCH...................................................................IFC SCHUNK Intec India Private Limited...................... 07 MANUFACTURING Bachem AG...............................................03, 34 & 35 BOSCH...................................................................IFC NETZSCH.......................................................OBC, 27 Priorclave Limited................................................... 43

SuppliersGuide

SCHUNK Intec India Private Limited...................... 07

Company................................................Page No. Bachem AG...............................................03, 34 & 35 www.bachem.com BOSCH...................................................................IFC www.boschpackaging.com India Lab Expo........................................................ 41 www.indialabexpo.com China Pharm.............................................17, 32 & 33 www.china-pharm.net NETZSCH Werbe- und Service- GmbH.........OBC, 27 www.netzsch.com Priorclave Limited................................................... 43 www.priorclave.co.uk

To receive more information on products & services advertised in this issue, please fill up the "Info Request Form" provided with the magazine and fax it, or fill it online at www.pharmafocusasia.com by clicking "Request Client Info" link.

1.IFC: Inside Front Cover 2.IBC: Inside Back Cove 3.OBC: Outside Back Cover

54

P h a rm a F o c u s A s i a

ISSUE - 20 2014

SCHUNK Intec India Private Limited...................... 07 www.in.schunk.com/machine-potential UBM India Pvt Ltd - CPHI&PMEC............IBC, 10 &11 www.cphi.com/india UBM India Pvt Ltd - PharmaLytica............36, 37 & 38 www.ubmindia.in/pharmalytica

www.pharmafocusasia.com

54

Mix with the world of pharma, products, people & solutions

2-4 December 2014

Bombay Convention & Exhibition Centre Mumbai, India

Network and do business

with 32,000 pharma professionals from all over the world @ CPhI & P-MEC India 2014!

CPhI India has always met our expectations. The quality of the visitor is very high and majority of the potential customers we have met will lead to additional business for us which has made our participation very worthwhile

Heldin, UK Trade & Investment

CPhI & P-MEC India is the single biggest event in India and anybody who is associated with Pharma should participate.

The quality of the visitor is pretty good and all the decision makers have been here. This time we had good walk-in along with good quality

Laxmikant, Mutisorb Technologies

CONTACT: Email: kumudini.bodha@ubm.com Call: +91 (22) 6172 7163 Email: rahul.deshpande@ubm.com Call: +91 (22) 6172 7165

www.cphi.com/india

Co-located with:

In partnership with:

Supported by: