Rare Diseases - Q1 2023

emotions.

Living with a rare disease doesn’t mean you have to struggle alone

Presenter

Nikki Lilly shares her experiences living with the rare disease arteriovenous malformation (AVM) and how she helps raise awareness.

Q: What are your interests/passions?

I started making videos online when I was eight, to cope with everything and find new interests and hobbies. I found such a love and passion for making videos online. Baking and makeup helped me express myself at a time when I felt very isolated from the world.

Q: How did you find out about your condition?

I was diagnosed at six years old, and it took a lot of referrals. There was such a lack of information on AVMs back then. It wasn’t even in the NHS directory.

AVM is a problem with the vascular system and is a condition I was born with. My AVM is on the right side of my face, top of my head and gums. A facial AVM affects three in a million people, so it’s extremely rare.

Q: How does AVM impact your day-to-day life?

Common symptoms include chronic pain, fatigue, swelling and bleeding. Bleeding is a big one; it’s also the most life-limiting for me.

I get life-threatening nosebleeds which can be really scary, and I never know when they’re coming.

You end up living life with a lot of anxiety and uncertainty. From an early age, my parents and I had to make life or death decisions regarding treatments and operations. Having a chronic disease is a constant day-to-day battle and rollercoaster of emotions.

Advancing health equity to improve the lives of people with rare diseases

WRITTEN BY Peter L. Saltonstall President and CEO, National Organization for Rare Disorders

For many of the roughly 7,000 identified rare diseases, those who are diagnosed are one in a million. Health equity is needed to improve the lives of people with a rare disease.

Q: How has the (Butterfly) AVM Charity helped you and others?

Because AVMs are so rare, online information is lacking and often outdated, especially back when I was diagnosed. As the first registered AVM charity, we wanted to provide emotional support to AVM sufferers and their families and talk to them about doctors and available treatment options worldwide.

In the United States, for a disease to qualify as rare, it must affect less than .06% of the population.

Living with a rare disease is an isolating experience. But while the number of people impacted by an individual rare disease is often quite small, rare diseases do not discriminate. They affect people of all genders, ages, races, ethnicities, socioeconomic statuses, religions and sexual orientations.

Fighting for health equity in rare diseases

The theme for Rare Disease Day 2023 is health equity — which gives us a chance to highlight the challenges the world’s 300 million rare disease patients face and what we can do to help.

that often involves visits to multiple doctors and specialists and countless tests.

Once they receive a diagnosis, rare disease patients face more challenges — since fewer than 10% of rare diseases do not have approved treatments. For conditions that do have treatments, patients are often unable to access them due to cost or where they live.

How to help people with a rare disease

Q: What action needs to be taken for rare diseases?

Firstly, raising awareness is vital. Many pharmaceutical companies are not willing to invest in an illness that occurs in such a small percentage of the population. Funding for research could not be achieved without volunteers who selflessly dedicate their time and efforts to help raise money — from running marathons to baking cakes.

Our researchers have now found one of the genetic mutations that cause AVMs. Focused research has the potential to provide breakthroughs; this hope keeps me — and people with a rare disease — going.

For those with rare diseases, health equity means that all patients and families would have a fair opportunity to achieve their best health and wellbeing, regardless of who they are, where they live and what disease they have. Unfortunately, rare disease patients face significant obstacles in achieving this ideal.

Obstacles to achieving health equity

For many, the obstacles begin with getting an accurate and timely diagnosis of their condition. The journey to diagnosis is often long and costly. For the average patient, it takes between five to six years to get an accurate diagnosis — a process

Health equity is possible by finding solutions to existing disparities and exploring ways to address the needs of every rare disease patient. Together, we can advocate for change by participating in campaigns and speaking up for policies in our respective countries that help rare disease patients. Together, we can advance breakthroughs that discover new treatments and medicines. The rare disease journey is not easy. But because the worldwide rare disease community is stronger and better organised than ever before, health equity can be more attainable.

We hope everyone will learn about the realities of rare diseases and be moved to take action and help create a better future that eliminates disparities by advancing research, public policy and access to care.

Dr Jennifer

Director of Research Policy, ABPI

INTERVIEW WITH Nikki Lilly Charity Campaigner, founder of Butterfly AVM charity, Digital Creator and

“UK genomics can transform the lives of people living with rare diseases.”

Harris

“Why we must all work together to beat childhood cancer.”

Kiki Syrad Director of Impact and Charitable Programmes, GOSH Charity

For the average patient, it takes between five to six years to get an accurate diagnosis.

WRITTEN BY Angelica O’Toole

Our researchers have now found one of the genetic mutations that cause AVMs.

Shaping a better future for people living with sickle cell disease in the UK

While referred to as ‘rare’ due to the smaller size of individual patient populations, rare diseases collectively are common, with 1 in 17 people affected.1

Rare disease communities are underserved, with only 5% of rare diseases having available treatment options.2 On Rare Disease Day 2023, we shine a light on one of those rare conditions, sickle cell disease (SCD).

What is sickle cell disease?

SCD is a rare genetic disease affecting approximately 52,000 people in Europe3 and 15,000 people in the UK,4 primarily of African, Mediterranean and South Asian descent.

SCD is a debilitating lifelong blood disorder affecting haemoglobin, a protein carried by red blood cells (RBCs) that delivers oxygen throughout the body.5 People with SCD form abnormal haemoglobin called sickle haemoglobin. 5 This causes RBCs to lose flexibility, becoming rigid, sticky and sickle shaped.5 Recurrent sickling process results in the breakdown of RBCs, blockages in capillaries and small blood vessels and haemolytic anaemia (low haemoglobin and low oxygen delivery in the body due to RBC destruction).5

Reduced oxygen delivery to tissues and organs means people with SCD experience progressive, life-threatening complications, including damage to major organs such as the liver, kidneys, lungs and heart, contributing to decreased quality of life and early death.6 Life expectancy is reduced by approximately 30 years compared to the general public.7

Improving care for people with SCD

Recent reports have described the urgent need for improved care and treatment for people living with SCD:

• The ‘No One’s Listening Report’ published by the APPG on Sickle Cell and Thalassaemia with the Sickle Cell Society, found inadequate levels of training and investment and low awareness of SCD among healthcare professionals. It called for positive change including mandatory training on SCD for nurses and guidelines to support healthcare professionals.8

• In January 2023, the NHS Race and Health Observatory commissioned the Sickle Cell Digital Discovery report, echoing the No One’s Listening report.9 Patients were exposed to negative attitudes; and during a sickle cell crisis, the NHS does not always provide patients with a reliably good experience, concluding the NHS should redesign sickle cell services.9

• A multinational survey commissioned by Global Blood Therapeutics, a Pfizer subsidiary, and conducted by Ipsos Healthcare of 1,345 people from 10 countries, highlighted the societal and economic burden SCD places on patients, caregivers and healthcare systems.10 The survey underscored that living with SCD goes beyond physical pain and significantly impacts the quality of life and mental health of both patients and caregivers.10 Patients with SCD also miss over three months of work or school every year due to SCDthus reducing earning potential.10

There is an urgent need for new conversations around SCD from a medical, socioeconomic and political perspective — industry, healthcare, government and professional bodies need to work together to help improve quality of life for SCD patients and caregivers in the UK to help ensure they receive the care and support they need.

References

1. The UK Rare Diseases Framework. Published 9 January 2021. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/ attachment_data/file/950651/the-UK-rare-diseases-framework.pdf [Accessed February, 2023].

2. Global Genes. Available from: Rare Disease Facts. [Accessed January 2023].

3. European Medicines Agency. https://www.ema.europa.eu/en/medicines/ human/orphan-designations/eu3182125. [Accessed February 2023]

4. Sickle Cell Society. About Sickle Cell. https://www.sicklecellsociety.org/aboutsickle-cell/. [Accessed January 2023]

5. National Heart, Lung, and Blood Institute. Sickle Cell Disease. https://www. nhlbi.nih.gov/health-topics/sickle-cell-disease. [Accessed February 2023].

6. Kato GJ, Piel FB, Reid CD, et al. Sickle cell disease. Nat Rev Dis Primers. 2018;4:18010. Available from: https://www.nature.com/articles/nrdp201810. [Accessed January 2023].

7. Piel et al. Sickle Cell Disease. New England Journal of Medicine. 2017;376:1561. DOI: 10.1056/NEJMra151086 5

8. The Sickle Cell Society and All-Party Parliamentary Group on Sickle Cell and Thalassaemia. No One’s Listening report. 15 November 2021. https://www. sicklecellsociety.org/no-ones-listening/ [Accessed 9 December 2022].

9. The NHS Race and Health Observatory. Sickle Cell Digital Discovery Report. January 2023. Available at:; https://www.nhsrho.org/wp-content/ uploads/2023/01/Sickle-cell-digital-discovery-report-designing-better-acutepainful-sickle-cell-care-January-2023.pdf [Accessed February, 2023].

10. GBT Sickle Cell Health Awareness, Perspectives and Experiences (SHAPE) Survey: Final Report. Data on File. (2022) (PP-UNP-GBR-2659)

WRITTEN BY Owen Marks

Head of Rare

Diseases UK, Pfizer

Paid for by Pfizer

Gene therapies are a promising treatment option for people with rare diseases living with genetic conditions. However, pricing remains an issue. Payment solutions must be identified to ensure gene therapies are available to those who need them.

Since the majority of rare diseases have genetic causes, it is encouraging that there are around 150 ongoing gene therapy clinical trials for rare conditions. We can therefore expect more gene therapies to become available in the coming years.

Gene therapy pricing challenges

Some gene therapies may be clinically effective for many years or decades. These long-term benefits are one of the reasons gene therapies are often considerably more expensive than other types of treatments. It is not possible for the National Health Service (NHS) and gene therapy manufacturers to know exactly how long a gene therapy will be effective when a price needs to be agreed upon. This creates more uncertainty, making it harder to determine what a fair price is.

Gene therapy payment options

Traditionally, manufacturers of new treatments have offered the NHS discounts where there is any uncertainty surrounding how effective a therapy is. However, some have argued that gene therapies would still be too expensive, even if large discounts were used.

One alternative payment option called ‘outcome-based payments’ would mean the NHS only pays for a gene therapy for as long as it is beneficial to the person receiving it. This option would require medical teams to collect data from people receiving gene therapies over a number of years. However, implementing outcome-based payments may be difficult due to the resulting administrative burden and high costs for the NHS, at a time when the NHS is already under increasing pressures.

Pricing challenges must not affect access

Those involved in pricing negotiations for gene therapies must continue engaging with each other, as well as the patient community, to ensure appropriate payment solutions are identified. These challenges must not prevent patients from accessing potentially life-changing gene therapies.

WRITTEN BY Kate Hanman UK Head of Rare Diseases, Costello Medical

UK genomics can transform the lives of people living with rare diseases

Many rare diseases have a genetic origin, so genomics — the study of a person’s genetic sequence — has the potential to reduce this timeline through quicker diagnosis and greater access to testing.

Patients with rare diseases often face an unpredictable journey known as the ‘diagnostic odyssey.’ When considering that the average process towards a diagnosis lasts eight years, this compares just two years short of Odysseus’s journey — and can be just as fraught.

Studies and findings in rare disease genomics

The 100,000 Genomes Project is an initiative to sequence and study the role our genes play in health and disease. It led to ‘actionable findings’ for 25% of rare disease participants to date.1

Whether it is conducting genetic tests to enhance diagnosis or researching new treatments using genetic data, harnessing the power of genomics has the potential to transform the lives of all patients, particularly those with rare diseases.

Using genomics in clinical research

Genomic testing can be used to improve diagnosis and patient care and for developing new treatments. The results of genomic tests can identify potential participants for clinical trials. Genomic data can provide biological insights that help understand rare diseases better and discover new drug targets.

The UK needs to collaborate globally on research, as rare disease patient populations are geographically dispersed. The sharing of data, knowledge and expertise through international research collaborations is equally as critical.

Growing the genomics workforce

We also need people in the UK’s genomics workforce with the right skills. Training in fields such as computational sciences, bioinformatics and data science is essential to understanding and interpreting genomic data. Upskilling the current

healthcare workforce in genomics is also a priority to ensure they can interpret the results from genomic tests and help patients understand their diagnosis and prognosis.

The way forward in rare disease genomics

The Genome UK and Rare Disease Framework implementation plans for England include actions to make these happen. These plans are a big step forward in delivering on the Government and industry’s shared commitment to fully harness the power of genetic medicine to transform care for patients. It builds on the recommendations of our report on genomics last year.2

The industry will continue to work with government and system partners to deliver on these commitments and help people with rare diseases feel the full benefits of the UK’s leadership in genomics.

References

1. https://www.genomicsengland.co.uk/initiatives/100000-genomes-project /rare-disease

2. https://www.abpi.org.uk/r-d-manufacturing/genomics-in-healthcare-andresearch/harnessing-the-uk-s-genomics-expertise-to-improve-patient-outcomes/

Scan the QR code to find out more about ABPI’s recommendations on genomics in our report ‘Harnessing the UK’s genomics expertise to improve patient outcomes.’

WRITTEN BY Dr Jennifer Harris Director of Research Policy, ABPI

Genomic testing can be used to improve diagnosis and patient care and for developing new treatments.

Gene therapies offer hope to the rare disease community – but how do we pay for them?

How cell and gene therapy offers hope to patients with rare ophthalmic diseases

Patients impacted by inherited retinal diseases — a group of rare genetic eye conditions — have had limited treatment options. Now cell and gene therapy offers them new hope.1,2

Inherited retinal diseases (IRDs) are rare genetic eye conditions which all have one thing in common: they affect people in different, debilitating and ultimately devastating ways.

Physical and mental impact of IRDs

“There are many types of IRDs, with over 300 causative genes described,” reveals Avril Daly, CEO of Retina International, a global umbrella organisation for patient-led charities and foundations that support research into rare, genetically inherited and age-related forms of retinal disease. “For instance, retinitis pigmentosa (RP) affects night and peripheral vision and, globally, 2 million people are estimated to live with it.” Other examples include Stargardt’s disease which affects central vision, the ability to see colour and causes sensitivity to light; and Leber congenital amaurosis (LCA), which can result in vision loss from early childhood.

The impact of IRDs can be damaging from a practical and psychological standpoint, says Daly. “When a young person is living with this kind of degenerative vision loss, they can’t engage in sporting activities or drive, which can impede the development of social groups. It also affects access to educational and career opportunities — it is fair to say that the wellbeing of those who live with IRDs is seriously impacted across the board.”

Using patient-centric approaches

To compound the issue, the majority of IRD patients are currently living with no available treatment options.3

Partnership simplifies and accelerates operational distribution of rare disease treatments

Specialist innovator drug companies with novel treatments for rare diseases can benefit from partnering with expert service providers who focus on managing the regulatory and supply chain complexity of distribution operations.

WRITTEN BY Mike Flatt Operations Director, Therismos

Expert distribution partners provide services to their specialist drug company clients, managing the complexities and removing the overheads but enabling the client to maintain control. This eliminates the need for their clients to establish and run regulatory-compliant distribution supply chain operations themselves.

Making rare disease treatments attainable

According to healthcare operations director Mike Flatt, this means patients with rare diseases benefit from accelerated access to treatment through established robust and cost-effective channels, while niche drug development companies benefit from the outsourced services enabling them to invest in further value-adding product development and commercialisation activities.

Now, however, the field of cell and gene therapy offers new hope,1,2 notes Marianthi Psaha, Global Head of Cell & Gene Therapy at Santen, a global pharmaceutical company specialising in ophthalmology. “We want to unlock the power of cell and gene therapies to restore vision, reduce the loss of social and economic opportunities and transform lives,” she explains.

The cell and gene therapies model is very different from traditional drug development, so it’s crucial for pharma companies involved in this new science to work closely with patient groups.

“In the field of rare diseases — with its small disease population and limited treatment options — it’s very important to understand the patient perspective and their unmet needs,” says Psaha.

At Santen, this can include discussions, roundtables and patient visits. “Ultimately, we want to capitalise on our knowledge, skills and capabilities to accelerate the development and delivery of cell and gene therapies that effectively target high unmet medical needs,” says Psaha. “In our Cell & Gene Therapy unit, we are committed to putting patients at the heart of our strategy.”

References

1. Wang AL, Knight DK, Vu TT, Mehta MC. Retinitis Pigmentosa: Review of Current Treatment. Int Ophthalmol Clin. 2019 Winter;59(1):263-280. doi: 10.1097/ IIO.0000000000000256. PMID: 30585930.

2. Zhang Q. Retinitis Pigmentosa: Progress and Perspective. Asia Pac J Ophthalmol (Phila). 2016 Jul-Aug;5(4):265-71. doi: 10.1097/APO.0000000000000227. PMID: 27488069.

3. Vázquez-Domínguez I, Garanto A, Collin RWJ. Molecular Therapies for Inherited Retinal Diseases-Current Standing, Opportunities and Challenges. Genes (Basel). 2019 Aug 28;10(9):654. doi: 10.3390/genes10090654. PMID: 31466352; PMCID: PMC6770110.

distribution company focused on supporting companies with a bespoke distribution service offering. This eliminates the WDA investment risk caused by potential delays in the pricing and reimbursement phase. It simplifies the work needed for a rapid launch of patient access to groundbreaking medicines for rare diseases.

Therismos is a specialist distribution company with the infrastructure in place and the experience across several health sectors and clients to professionally offer a distribution service at the optimal time.

Simplified and quicker access to rare disease treatments

Companies must have a Wholesale Distribution Licence – also known as a WDA (Wholesale Distribution Authorisation) – before they can distribute new drugs to patients. Acquiring, maintaining and operating a WDA requires systems, procedures, premises and qualified staff.

Companies often embark on this themselves as their drug nears commercialisation. Besides the cost, it can typically take up to nine months to set up, apply for a licence and be successfully audited and approved by a health authority. To avoid this, companies may enter into distribution licencing deals with organisations but in such arrangements control of the product is lost.

A third, lesser-known route, is through a partnership with a specialist

Cost-effectiveness for rare disease treatment supply

With a bespoke distribution partnership arrangement, companies can avoid the need to set up a local UK business entity, staffed with a supply chain and quality team, and order management and finance functions. They can avoid the investment required to obtain and manage a WDA plus the setting up and management of contracts with local partners for product storage and movement.

Additionally, the specialist distribution service company offers clients benefits from economies of scale and a means by which supply can be switched on rapidly and only when required. Unlike distribution licensing deals, clients don’t lose control of their product and the whole process is simplified for them.

Paid for by Santen

INTERVIEW WITH Marianthi Psaha

Global Head of Cell & Gene Therapy, Santen

WRITTEN BY Tony Greenway

INTERVIEW WITH Avril Daly CEO, Retina International

Accelerating rare disease drug discovery by combining research and therapeutics development

Rare disease research and drug discovery requires collaboration between patients, organisations, researchers and clinicians. Only then can treatments for the millions of people with a rare disease become a reality.

Only a small percentage of people living with a rare disease have an approved therapy for their condition, presenting a great challenge to global health.

Turning promise into action

Most rare diseases have a genetic cause, resulting from variations in a person’s DNA. With recent developments in genomics and the ability to quickly and cost-effectively sequence patients’ DNA, there is now the exciting opportunity to design personalised medicines for rare diseases.

The Oxford-Harrington Rare Disease Centre (OHC), a partnership between the University of Oxford and Harrington Discovery Institute, is combining world-leading research with expertise in therapeutics development to accelerate the discovery and delivery of new treatments for rare diseases.

New hope for patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease characterised by progressive muscle degeneration and weakness. DMD is caused by a defect in a gene that makes dystrophin, which acts like a shock absorber when muscles contract. Without dystrophin, muscles progressively become damaged and weakened. People with DMD typically do not live past their 30s.

Angela Russell, Professor of Medicinal Chemistry at Oxford, has been working on a protein called utrophin, which was found to function similarly to dystrophin in protecting muscle. Her group has discovered new classes of molecules that increase utrophin production. Her project was recently selected by the OHC for further drug development and commercialisation support.

Innovative technologies: DNA repeat expansion disorders

Huntington’s disease (HD) is a fatal disease that causes certain brain cells to degenerate. Symptoms include uncontrolled movements and difficulty walking. HD results from a disease-causing DNA repeat expansion, wherein a segment of DNA within the huntingtin gene expands.

Edward Grabczyk, Professor of Genetics at Louisiana State University and Harrington Rare Disease Scholar, identified that the genetic mutation underlying DNA repeat expansion in

HD is driven by the protein MLH3. He designed novel oligonucleotide drugs to decrease MLH3 activity, which in turn should slow or stop the progression of the disease. Grabczyk’s approach may enable the treatment of other related disorders, and today, his technology is licensed with Takeda Pharmaceuticals.

The OHC has a philanthropically funded programme focussed on Friedreich’s ataxia, a neurodegenerative rare disease with a related disease mechanism. It works with an international network of patients, foundations, researchers and clinicians towards developing new therapies for the one in 40,000 people affected by this disease.

Advancing treatments towards patients Harrington Discovery Institute is an international drug discovery and development organisation established to address unmet therapeutic needs. It provides comprehensive support to leading scholars and entrepreneurs across academic centres in the US, UK and Canada. The focus is on medical breakthroughs that show great promise but would not otherwise advance to clinical trials.

By concentrating on philanthropic, scientific and business development resources during the early, high-risk stage of drug discovery and creating pathways toward commercialisation, Harrington drives the progress of therapeutic candidates towards further investment and clinical trials.

Partnering for cures

The University of Oxford has hundreds of researchers working on a range of rare diseases and cutting-edge therapeutics. Its new Institute of Developmental and Regenerative Medicine (IDRM), where the OHC is based, aims to develop new drugs and therapeutic strategies for neurological, cardiovascular and immune diseases.

Matthew Wood, Director of the OHC, Professor of Neuroscience at Oxford’s Department of Paediatrics, and Director of the MDUK Oxford Neuromuscular Centre, recognises the need for partnership with the global rare disease community in achieving the goal of accelerating rare disease therapeutic development. Wood explains: “There are significant challenges in meeting the needs of rare diseases. With advances in genomics and drug development and delivery, we are now in a position to make a difference for people who have had little hope of finding a treatment.”

INTERVIEW WITH Professor Matthew Wood Director, Oxford-Harrington Rare Disease Centre

Although individual rare diseases are rare, collectively they represent about one-third of human diseases.

INTERVIEW WITH

Jonathan S. Stamler, MD President, Harrington Discovery Institute

Finding hope in a global movement to cure rare diseases

Global collaborations are needed to meet the challenges of rare disease and to drive progress in scientific research towards delivering therapies for people living with rare diseases.

Individuals with rare diseases and their families typically have a long journey to a diagnosis with little hope for a cure.

The Oxford-Harrington Rare Disease Centre, a partnership between the University of Oxford and Harrington Discovery Institute, brings together the resources and capabilities needed to accelerate novel treatments for patients living with a rare disease.

Individually rare, collectively common There are 400 million people across the globe living with a rare disease, affecting 1 in 17 people during their lifetime. Although individual rare diseases are rare, collectively they represent about one-third of human diseases. Fewer than 5% of rare diseases have approved treatments.

The Oxford-Harrington Rare Disease Centre (OHC) was established to accelerate treatments and cures. Its work supports the drug development life cycle from early drug discovery to preclinical studies, clinical development, regulatory approval and ultimately through to commercialisation.

“This affiliation represents a commitment to patients first and a tremendous opportunity to improve the health and outcomes of those living with a rare disease,” says Jonathan S. Stamler, MD, President of Harrington Discovery Institute.

for philanthropists to combine their resources to magnify the impact of their medically related giving, whether on a specific disease or across a broader spectrum.

“For the first time in Cooper’s life, someone understood our son. Not only did they understand our medical mystery, but they also provided us with the most impactful gift we could’ve imagined, hope. Harrington turned on the lights in our blacked-out world,” says Jordan New.

From diagnosis to doctorate

Christian Lantz was diagnosed at age eight with the rare neuromuscular disease, limb-girdle muscular dystrophy. His diagnosis inspired his interest in science and the ambitious decision to pursue a doctorate in neuromuscular disease research.

Lantz, now a doctoral student in the National Institutes of Health (NIH) Oxford-Cambridge Scholars Program, researches a group of rare diseases originating from mitochondria, causing amyotrophic lateral sclerosis (ALS), a form of dementia, and a form of spinal muscular atrophy (SMA). He is mentored by the OHC Director, Professor Matthew Wood, at the University of Oxford. His project links the immense resources of the NIH and National Center for Advancing Translational Sciences (NCATS) in the US with disease-specific expertise and UK institutions with a shared mission. These invaluable projects create the global networks that will bring together the funders, researchers, drug development experts, foundations and regulatory bodies that will drive rare disease drug delivery.

Finding hope and community

Sophie and Jordan New learned through genetic testing that their young son, Cooper, has FBXO11, an intellectual developmental disorder. This ultra-rare disease occurs in less than one in a million people.

Cooper’s parents, and grandparents Rusty and Liz Cooper, set out to learn as much as possible about FBXO11 and any potential treatments. Rusty, a financial advisor at Morgan Stanley, learned about Harrington Discovery Institute at University Hospitals in Cleveland, Ohio through Morgan Stanley GIFT CuresSM powered by Harrington Discovery Institute. This programme provides opportunities

“I feel very fortunate to be involved in rare disease research having experienced living with a rare disease. The rate of advancements in gene therapy and research gives me hope that many more rare diseases will be addressed with treatment options in the future,” says Lantz.

Help us cure rare diseases

We invite you to join us in supporting the OHC and its mission to advance cures for rare diseases. Your support will help us to continue to fund drug discovery and development and provide the resources needed to advance promising scientific breakthroughs into treatments for patients. Together, we can make a difference in the lives of those living with rare diseases and their families.

I feel very fortunate to be involved in rare disease research having experienced living with a rare disease.

INTERVIEW WITH Christian Lantz DPhil Candidate in Biomedical Sciences, NIH-Oxford

SPREAD WRITTEN BY Dr Julie Stevens Programme Manager, Oxford-Harrington Rare Disease Centre, University of Oxford

INTERVIEW WITH Sophie New, Jordan New and Cooper New

These services offer hope for a better future to people living with rare conditions and their families.

Benefits of collaborative care for people living with rare conditions

Collaborative care is essential for people living with rare conditions and their families to minimise the impact of health appointments. It will help healthcare professionals to work together effectively and provide high-quality care.

Many rare conditions are lifelong and complex. People affected by rare conditions need support and expertise from a range of healthcare professionals such as hospital consultants, specialist nurses and physiotherapists, to name a few. This can mean having multiple appointments across different settings and on different dates.

and tests) that takes place over two days. Over these two days, there are around 10–15 healthcare professionals involved in Hassan’s care.”

Professor Timothy Barrett is a paediatrician at the clinic. He says: “The Alstrom syndrome clinics are a tri-partite model with a specialist nurse, transition coordinator and family support worker from the charity Alstrom Syndrome UK.”

WRITTEN BY Louise Fish Chief Executive, Genetic Alliance UK

Collaborative care can ease pressures

For Rare Disease Day 2023, we are highlighting how well-coordinated care can make a real difference in people’s quality of life.

For example, Alstrom syndrome is an ultra-rare, life-limiting condition that affects multiple parts of the body. People living with the condition experience increasing problems as they grow older, including problems with their vision, hearing, sense of smell and poor control of their bodily functions.

There is a highly specialised service for treating Alstrom syndrome at a hospital in Birmingham delivering Alstrom syndrome clinics around six times a year through a one-stop shop model. Kez Hayat’s son, Hassan, has benefited from the coordinated care provided by the service.

Complete expertise in collaborative care

Hayat says: “Each year, we travel to the hospital for a ‘full body MOT’ (measurements, observations

“The specialist nurse coordinates the medical aspects of care and liaises with schools to educate teachers about the medical impact of the condition. The transition coordinator supports individuals who may be moving into senior school or employment.”

“They can help families get an educational healthcare plan (EHCP) at school or claim any benefits or personal independence payments they are entitled to. The family support worker coordinates travel and accommodation for patients and families to come to the clinic.”

Helping families through rare disease care

There is a range of models for care coordination emerging, including national services for ultra-rare conditions like the Alstrom syndrome clinic or regional rare disease hubs for more common rare conditions. These services offer hope for a better future to people living with rare conditions and their families.

People living with the condition experience increasing problems as they grow older, including problems with their vision, hearing, sense of smell and poor control of their bodily functions.

Help rare disease patients by involving them at every stage of development

Inclusion of the ‘patient voice’ is critical at all stages of research and drug development, starting from clinical trial design, through the regulatory processes — and during access discussions.

Asmall or rare patient population can affect clinical trial recruitment and slow down the development of medicines.

Data generation

We should explore alternative study designs, developed closely with regulators, involving fewer patients but still delivering data that allows appropriate evaluation.

We are actively exploring new methods of evidence generation with an emphasis on supplementing clinical trial data with external/ historical data, as well as pre and post-approval real-world datasets.

Regulators are moving in this direction too, however, people living with a rare disease continue to tell us their concerns and stress the need for greater urgency.

Different measures

People often experience difficulties from the disease which extend beyond symptoms that can be measured in traditional clinical trials. These symptoms can be as impactful and relevant to patients, and, therefore, with better Patient Centred Outcome Research (PCOR) we can establish what matters most to people living with a rare disease.

Effective listening

We should work closely with patient organisations and Centres of Excellence to listen and learn about the patient experience. We must truly respect patients as the experts in living with their condition, as only they can tell us what they really need.

As part of our commitment to partnering with people living with a rare disease, we provide opportunities for people to speak about their personal realities and describe how their condition impacts life for themselves and their families. These insights can help improve understanding of symptoms and disease management and are invaluable in clinical trial design.

The scientific community, regulators, payers and industry should partner together in listening to and collaborating with patients, to embrace the patient view on what access to the right care would mean for them.

Industry must communicate to healthcare providers and payers the value new options provide above the treatment costs alone. This could include wider societal benefits and less tangible, but equally important, quality of life and mental health benefits for patients, families and caregivers. By working together, we can create a greater impact for people living with a rare disease.

WRITTEN BY Charl van Zyl Executive Vice President, Neurology Solutions & EU/International Markets, UCB

Paid for by UCB

A global community demands visibility for people with a rare disease

People living with a rare condition experience a kind of invisibility which exacerbates inequity, discrimination and injustice. Imagine a community of over 300 million people fighting to be seen.

On Rare Disease Day 2023, Rare Diseases

International (RDI), a global network of rare disease organisations, has a simple call to action: that the world sees and recognises people living with a rare disease. With this goal in mind, on 28 February 2023, the network will host a virtual event organised in partnership with the Rare Disease Day campaign to spotlight rare disease groups around the world and help raise awareness among the public, policymakers and healthcare systems.

Recognition is a matter of life and death

In many countries, rare diseases are virtually invisible to healthcare systems and providers. Primary care clinicians are regularly unable to identify and effectively treat conditions to which they may have limited exposure. The result is a delayed diagnosis, misdiagnosis and inappropriate treatment or clinical management leading to disease progression with life-threatening consequences. The majority of rare diseases do not have an effective treatment as research into conditions that affect fewer people is not prioritised, and companies find financial incentives insufficient to drive the development of therapies. Where treatments are available, high pricing and unequal access mean that people fail to receive potentially lifesaving therapies and care. This is especially true for communities in low and middle-income countries.

Rare disease invisibility is social injustice

In the absence of disaggregated data, the social determinants of health — including work, gender, access to social services and education — are often left out of policies on rare diseases. For example, issues such as isolation and stigma, access to occupational opportunities and the heavy cost of rare diseases on families are often excluded from social support initiatives.

Policymakers wrongly conclude that other frameworks, such as broader health and disability policies, sufficiently cover people living with a rare disease. However, rare conditions require specific attention, which focuses on the complexities presented by rarity.

A global shift for rare disease communities

There are positive signs that this previously unseen community is gaining visibility. As many countries do not have a definition of what constitutes a rare disease, RDI, working with the World Health Organization (WHO), has developed an international description of rare diseases to help inform policymakers worldwide.

WRITTEN BY Durhane Wong-Rieger President, RDI Council

WRITTEN BY Hlawulani Mkhabela Strategic Engagement Manager, RDI

In many countries, rare diseases are virtually invisible to

This Rare Disease Day 2023, RDI will dedicate its social media platforms to national rare disease groups worldwide using the hashtag #SeeRare to help shed the cloak of invisibility and demand attention and further action. Catch the #SeeRare event at 14.00 on the Rare Disease Day Facebook Live stream.

In the UK, there are over 3 million people living with one of a plethora of different rare diseases. So while by definition some diseases affect only a small number of people, the totality of people affected is significant,” explains David Worthington, Field Medical Advisor for Rare Disease at CSL Vifor UK.

David adds: “We want to be a partner for our healthcare community not just by being a medicines manufacturer, but by working with patient groups, as well as the NHS in the UK.”

Partnering with rare disease patients

CSL Vifor UK works with patients’ organisations by helping them become aware of advances in knowledge about rare diseases and their management. They also collaborate with partners in the rare disease community at a local and global level to develop resources relevant to patients, carers and anyone affected by these conditions. To successfully support the rare disease communities, it is important that the health system recognises the benefit and value of different disease management solutions — either through therapeutic interventions, uptake of technologies or access to care.

Pace of clinical trials and innovation

Milos Petrovic, the company’s UK Medical Lead for Rare Diseases says: “In the last 15 years or so, there have been major technological advances, such as genetic testing and population studies extending across millions of

people — made possible in part by better use of computing power and advances in genomic research.

“Combined with the advances in basic sciences, this means we are now beginning to understand some of the specifics of how a certain rare disease affects the immune system, for example. This is crucial for studying the initiation and progression of the disease.

“Once researchers come up with a good idea, that’s where pharmaceutical companies can come in to help continue the work,” says Worthington. “We support the clinical development of potential products to assess whether they may become medicines. As a company, our pipeline of products focuses on rare diseases which are autoimmune in nature and often involve the kidney in one way or another.”

Data-gathering difficulties

With over 30 million people across Europe living with various rare diseases, there is a lot of information to be gathered and shared. Understanding each rare disease and how it manifests in each person affected is crucial to helping health practitioners understand them.

Worthington says that part of the problem in supporting rare disease patients is gathering data. “For example, we’ve been supporting a project looking into rare vasculitis by identifying how registries across Europe can be interrogated to increase the number of patients available for meaningful research

— to discover missing facts and develop better predictive tools to help doctors choose the best options for individual patients.”

Regulatory approval

Once new medicines obtain regulatory approval, it is necessary to assess their cost-effectiveness in order for them to become accessible to patients.

Joe Wildy, Head of External Affairs at CSL Vifor UK, says: “It’s challenging for Health Technology assessment (HTA bodies) to make concrete decisions around the cost-effectiveness of medicines for rare diseases. This is due to the small number of patients involved in clinical trials, compared to other diseases which HTA bodies are more used to looking at. It is harder for them to make clear decisions on cost-effectiveness with less data. So that is why it is really important that the patients’ voice come through clearly in the decision-making process.

“Because the regulators continue to create an environment where research into new drugs is encouraged, we will be able to continue working with patients’ organisations, clinicians, researchers and the NHS to help ensure that there are effective interventions for the rare disease community,” concludes Worthington.

A ‘rare disease’ is generally defined as a condition that is known to affect less than one in 2,000 people. However, there are over 7,000 possible rare diseases for which patients may need help.

It’s not that rare altogether: many rare disease patients need help

To successfully support the rare disease communities, it is important that the health system recognises the benefit and value of different disease management solutions.

INTERVIEW WITH David Worthington Field Medical Advisor, Rare Disease, CSL Vifor UK

WRITTEN BY James Martin

INTERVIEW WITH Milos Petrovic Medical Lead Rare Disease UK, CSL Vifor UK

INTERVIEW WITH Joe Wildy Head of External Affairs, CSL Vifor UK

Why we must all work together to beat childhood cancer

Investment in research has significantly improved survival rates, but cancer remains the most common cause of death in children aged 1 to 14 in the UK.

Every day, around five children are diagnosed with cancer in the UK. This is often the start of a long and difficult journey for these children and their families. All childhood cancers are rare, but Great Ormond Street Hospital (GOSH) sees the rarest and most complex cases from across the UK. With the support of vital funds from Great Ormond Street Hospital Children’s Charity (GOSH Charity), they have developed life-saving medical breakthroughs that have given hope to seriously ill children from across the globe. However, the journey towards beating cancer is far from over.

A long history of pioneering cancer treatment

Fifty years ago, only 40% of children diagnosed with cancer survived. But with the help of pioneers from the hospital, survival rates have more than doubled. Groundbreaking research has helped drive forward kinder and more effective treatments and surgical techniques. Since the hospital opened in 1852, research has been central to diagnosing and treating cancer in children. GOSH is now leading the way in CAR-T therapy, which reprogrammes the body’s own immune cells, called T-cells, to attack

cancer cells. In 2018, it became the first hospital in the UK to use CAR-T therapy to treat patients with acute lymphoblastic leukaemia as part of standard care.

In 2022, the Charity awarded a grant to a team at GOSH and University College London to develop a new CAR-T therapy for a rare and aggressive type of brain and spinal tumour, diffuse midline glioma (DMG).

This form of cancer has some of the worst outcomes for children, but the trial could be a first step towards developing effective treatments for DMG and other high-risk brain tumours that can be devastating to families.

More recently, 13-year-old patient Alyssa made headlines after becoming the first person in the world to be treated with a novel CAR-T therapy — created using a technique called base editing — for her previously incurable leukaemia. Early funding from the Charity helped make this possible.

Working to eliminate childhood cancer

The progress has been incredible. But we are committed to going even further to give hope to children with cancer. With our dedicated fundraisers, inspiring families and extraordinary clinical staff and researchers, we can turn the tide on childhood cancer once and for all.

WRITTEN BY Dr Kiki Syrad Director of Impact and Charitable Programmes, GOSH Charity