Blood Health and Life Sciences by Mediaplanet_USA

A Mediaplanet Guide to Blood Cancer, Treatment, and Medical Technology

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Health and Life Sciences SEPTEMBER 2022 | WWW.FUTUREOFPERSONALHEALTH.COM An Independent Supplement by Mediaplanet to USA Today Why access for all is key for blood cancer research 04Three ways for life science companies to capitalize on industry trends 03 Why you should be proactive about your blood cell count as you age 06 SEPTEMBER is Blood AwarenessCancerMonth

uring the last two decades, technolog ical advancements have delivered groundbreaking new insights about the molec ular activities of cancerous cells. Most significantly, we have learned that every per son’s cancer — like every per son — is biologically unique. Guided by these discoveries, some physicians have begun to embrace a new way of treating cancer patients called person alized

All

Health systems across the world are studying the longterm effects that broad-based MCED testing may have on healthcare costs and patient outcomes. Some providers have become early adopters.

The impact personalizedofmedicine

are credited

unless otherwise specified. This section was created by Mediaplanet and did not involve USA Today. INQUIRIES: US.EDITORIAL@MEDIAPLANET.COM AND US.ADVERTISE@MEDIAPLANET.COM PLEASE RECYCLE Following recent discoveries about the molecular activities of cancerous cells, some physicians are embracing a new way of treating cancer patients called personalized medicine.

Personalized Medicine Is the Future of Cancer Care

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Multi-cancer early detection (MCED) tests can spot dis ease-associated genetic mate rial and proteins circulating in the blood streams of seem ingly healthy people. Such testing promises to deliver unprecedented benefits to patients and health systems by finding cancers at earlier stages, when they may be eas ier and less expensive to treat.

Oncologists can use genetic tests to identify the unique set of oncoproteins fueling the growth of each patient’s can cer. Targeted therapies disrupt specific oncoproteins.

Targeted therapies

attack cells that exhibit can cer-associated proteins.

Targeted therapies, cell-based immunotherapies, and MCED tests are hallmarks of a new era of personalized medicine in cancer care. By providing physicians with new oppor tunities to alleviate the root causes of cancer and detect cancers at earlier stages in their development, person alized medicine can enhance the efficiency and effective ness of cancer care. n

Cell-based immunothera pies are designed to teach the immune system to rec ognize and destroy cancerous blood cells. To administer the therapies, scientists extract and genetically modify a patient’s immune cells to

Multi-cancer early detection testing

Cell-based immunothera pies are believed to have cured some leukemia patients. The FDA has also approved cell-based immunotherapies for the treatment of some lymphomas and multiple myelomas.

plans that are tailored to each individual. Targeted therapies, cell-based immunotherapies, and multi-cancer early detec tion tests are playing leading roles in advancing the frontiers of personalized medicine.

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@MEDIAPLANETUSA @FUTUREOFPERSONALHEALTH Publisher Claire Hines and Shannon Ruggiero Business Developer Joelle Hernandez Managing Director

Alsomedicine.referredto as precision medicine, personalized medi cine focuses on understanding and influencing the unique set of cancer-related molecular interactions occurring within each patient’s body.

The goal is to address the root causes of each patient’s disease and develop treatment

The U.S. Food and Drug Administration (FDA) has approved targeted therapies for more than 30 types of genetically defined cancers, including certain forms of breast, lung, and colon cancers. immunotherapiesCell-based

Lincoln Nadauld, M.D., Ph.D., CEO, Culmination Bio Jordan Hernandez Kayla Mendez Joelle Hernandez photos to Getty Images

Lead Designer

Designer Christine Foltz Lead Editor Dustin Brennan Copy Editor Griffin Cronk Director of Content and Production

Cancer occurs when genes mutate inside of otherwise healthy cells. The mutations cause cancerous cells to pro duce dysfunctional proteins, called oncoproteins, that prompt uncontrolled cellular reproduction. The rapidly spreading cancerous cells crowd out healthy ones, dis rupting the body’s ability to function normally.

Targeted therapies are designed to disrupt the activ ity of mutated proteins that promote cancer growth.

For example, the drug dosing discussed above require under standing of regression, classifi cation, clustering, dimension reduction, and clinical termi nology and concepts. A basic understanding of algorithms, such as decision tree, linear regression, and neural net works is also needed for ML.

Few industries have greater promise than the life sciences industry, where cures for devastating diseases like cancer loom on the horizon.

ers, consultants, tech vendors), might include academics, futurists, and businesses from otherTheseindustries.nontraditional part ners can bring fresh points of view to the challenge of digital transformation. They also can help provide the financial and intellectual capital companies need to create innovative and open ecosystems of healthcare products and services and gain first-mover advantage.

1The Washington Post, “Longtime HIV patient is effectively cured after stem cell transplant,” Mark Johnson, July 27, 2022.

Understanding and Building a Skill Set for Machine Learning With Drug Dosing

priate ML algorithm, mathe matical formulas, parameters, approximate confidence levels, and statistical modeling proce dures are all basic concepts to apply. Fundamental computer science, such as data struc tures, algorithms, space and time complexity, and different programming languages like R and Python for ML and SQL for database management, is another important skill for ML.

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utors, healthcare providers, and even large-scale technol ogyLifeproviders.sciences firms can harness that data to inform product development and deci sion-making.Finally,keep cybersecurity at the forefront of digital trans formation strategy. Cyberse curity is viewed as critical by customers, business partners, investors, and other stakehold ers, and without their trust, life sciences firms will struggle to win their support and achieve their goals. n

Charting the Path to a Brilliant Future

This is an excerpt from an article recently published in the Journal of AHIMA in which AHIMA22 presenter

When selecting the appro

Soft skills in ML, such as communication, prob lem-solving, and critical thinking, are equally import ant when working with ML to convey your technical skills to non-technical peo ple, solve ongoing problems, and make better decisions. n

Shannon H. Houser, Ph.D., M.P.H., RHIA, FAHIMA, and co-author R. Jeffrey Harris, RPH, MSHI, take a closer look at the role of machine learning as this technology evolves.

First, embrace a partnership approach to digital transforma tion. With so much changing so fast on so many fronts, no company can hope to navigate digital transformation on their own. Success will depend on working with a diverse eco system of partners that, in addition to the usual suspects (e.g., contract research organi zations, contract manufactur

Second, develop a robust data architecture and data eco system built not just around internal data, but also data from an array of external part ners, including product distrib

Machine learning (ML) is a subset of artificial intelligence (AI) that uses reinforcement learning with human-like levels of intelligence to predict outcomes and improve task performance.MLiswidely applied in healthcare, including phar macy practices. It can be used to calculate dosages in special populations that are difficult for traditional human com puting.There are, however, chal

KPMG has identified three key ways life sciences com panies can speed their digital transformation agenda and extract maximum value from it — for themselves and the people depending on their innovative agendas.

Skills needed for machine learning

Some basic technical skills are needed when working with ML. Those skills include applied mathematics, com puter science fundamentals

To learn more, visit life-sciences-technology-http://institutes.kpmg.us/healthcare-life-sciences/blog-series.html

lenges in data management and analytics, and special skill sets are needed when working with ML in drug dosing appli cations.

Justin Hoss Principal,KPMGAdvisory,US

Data in general are fun damental constructs for ML. When building data modeling, it involves data structures, and the patterns of the data.

and programming, data modeling and evaluation, algorithms used in ML, and natural language processing.

Just in the past year, research ers have identified another patient likely cured of HIV after receiving transplanted stem cells containing a virus-defeat ing mutation. 1Examples like this point to a bright future for life sciences organizations, but capitalizing on the opportunity will require ongoing invest ment in digital transformation not just in research laborato ries, but across the enterprise.

Shannon H. Houser, Ph.D., M.P.H., RHIA, FAHIMA, and R. Jeffrey Harris, RPH,

Soft skills are also neces sary characteristics for deliv ering your technical skills more effectively.Mathemat ics, such as linear algebra, probability, statistics, and multivariate calculus, are fundamental skills in ML.

Recent advancements in the field of hematology offer many reasons to be optimistic about the future, but efforts in promoting diversity, equity, and inclusion (DEI) within hematology will also have a real impact on that future.

At the same time, immuno therapies are moving beyond malignant disease to improve outcomes in a broader range of disorders. Research into stem cell transplantation, cellular therapy, transfusion medi cine, and other cutting-edge immune-based therapies is yielding a deeper understand ing of the mechanisms of hematologic disease and revo lutionizing treatment.

While the advances in research in hematology are exciting, they’re only half the story. Initiatives in diversity, equity, and inclusion are not only vital in terms of the research and treatment of blood cancers and other disor ders like leukemia, lymphoma, and myeloma, they are also crucial to supporting both the patient community and the professionals doing the research and providing the care.Diversity and access are crucial to the success of clini cal trials, and increased access to hematologic healthcare for underserved populations serves a basic human right. In order to ensure awareness and access to everyone deal ing with blood cancer or other blood disorders, a wealth of resources and initiatives have been established:

ticipation is crucial.

• The CLL Society promotes increased equitable access through a dedicated focus on its web page and by provid ing resources and data that patients and their caregivers can use to combat the sys temic bias that often affects blood cancer outcomes.

Whether you or a loved one are dealing with a disease like leukemia, or if you’re a pro fessional in the field of hema tology, there are resources available to get informed, to get up to date about the issues surrounding equitable access — and to get involved. n

like single-cell sequencing have already had a tremen dous impact, and gene editing holds the potential to revo lutionize how hematologists and other healthcare providers treat blood disorders.

Jeff Somers

• The MPN Research Foun dation, which pursues new treatments for the group of blood diseases known collec tively as ofpublicnessatedneoplasmsmyeloproliferative(MPNs),hascreasocialmediaawarecampaigntoeducatetheabouttheimportanceclinicaltrialsandwhypar

Research into the treatment and prevention of blood can cers is producing exciting results. Aside from the excit ing developments in CAR T-cell therapies, advances in gene discovery science combined with the use of advanced analytic platforms

• The MDS Foundation has launched its Move for MDS program of community walks to raise awareness, push research, and encour age support for people affected by myelodysplastic syndromes.

In the wake of a global pandemic that saw people with blood cancers suffering a much higher mortality rate from COVID-19 infections, an expanding understanding of the ways infectious diseases and blood cancer intersect promises to save even more lives in the future.

The Future of Treatment and Inclusion in Blood Cancers

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Better diversity, equity, and inclusion measures in blood cancer research can improve outcomes for many patients.

millions of people every day — they represent 10% of all new cancer cases, and 9% of all cancer-related deaths. Every improvement of outcomes will save — and improve the quality of — those lives.

• The International Myeloma Foundation has established the M-POWER project as part of its Diversity Initiative. The project’s goal is to improve the short- and long-term out comes for African Americans diagnosed with this blood disease by improving aware ness and access to treatment and resources.

“Turn it Red” Campaign during Blood Cancer Aware ness Month, seeking to pro mote awareness of the work needed in the fight against blood cancers like leukemia, lymphoma, and myeloma by lighting up iconic buildings and public spaces in red.

lood cancers like myelomalymphoma,leukemia,andaffect

• The Leukemia & Lymphoma Society has launched its

Improving outcomes

Diversity and inclusion

• LLS’s Patti Robinson Kaufmann First Connection Program® — a free service that matches blood cancer patients and their loved ones with trained peer volunteers who have shared similar

experiences. Young adults can receive or volunteer to offer peer support.

Aside from physical side effects, the psychological and psychosocial effects of a cancer experience can be detrimental to young adults as they nav igate their diagnosis, where they are in life, and their rela tionships. Treatment can be isolating and might limit or prevent cancer patients from participating in regular rou tines and activities.

• Support groups — local, in-person groups that provide mutual support and educa tion to members who may feel a little less alone by meet ing with others whose situa tions are similar to their own.

• LLS Community — an online community that features a group specifically devoted to the young adult cancer com munity.

acing cancer at any age is dev astating, but for young adults ages 18-39, a diagnosis comes with unique challenges and consid erations.Atatime when individu als in this age group are likely embarking on new journeys in their education, profes sional careers, relationships, and more, cancer can bring their lives to a screeching halt. Treatment can cause long-term health complications, such as

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Coping With a Cancer Diagnosis as a Young Adult

In addition to the pro grams listed above, any patient, family member, or caregiver affected by a blood cancer diag nosis is encouraged to contact an LLS Information Specialist. These trained oncology pro fessionals offer one-on-one, personalized support through out the entire cancer journey into survivorship, providing accurate, up-to-date informa tion about blood cancers, clin ical trials, nutrition resources, and more, as well as help navigate financial and social challenges they might face. n

Melissa Valentino, The Leukemia & Lymphoma Society

Young people who are diagnosed with cancer need community and support. The Leukemia & Lymphoma Society offers a variety of programs designed to help.

free programs and support services LLS offers to all those affected by blood cancers, and features resources and groups dedicated to young adults. They connect young adult patients and survivors with others affected by blood cancer and with LLS’s trained oncology professionals, allowing them to share experiences, ask ques tions and seek support and information about their disease and experience.

“Experiencing cancer at any age is difficult,” said Karen DeMairo, vice president of education, support, and inte gration for patient and profes sional programs at The Leu kemia & Lymphoma Society (LLS). “For young adults work ing toward future goals, there are special considerations and having an adequate support system is Connectingcritical.”with others who have experienced or been affected by blood cancer in some way can be a valuable source of support.

Kyle Frazier Savannah State Univ. Football Player and Lymphoma Survivor

“I love and cherish LLS for the connections I made through their community,” said Kyle Frazier, lymphoma survivor and Savannah State football player. “I met and connected with so many won derful people who I still talk to today while in remission.” Fra zier remains involved with LLS by volunteering his time and support to other blood cancer patients.Below are some of the many

• Weekly Online Chat — an open forum for young adults dealing with cancer and can cer survivorship moderated by oncology social workers.

an increased risk of developing secondary cancer later in life, compromised organ function, and fertility issues.

Advocacy

An estimated 60,000-170,000 Americans live with MDS. Each year, 12,000-20,000 new cases are reported in the United States. Worldwide, an estimated 87,000 new cases are diagnosed Diagnosingannually.someone with

Symptoms and diagnosis

Many patients with the con dition don’t experience any symptoms. MDS may reveal itself through routine blood work, such as a reduced red cell count or a low hemocrit.

well as providers in the field. The foundation is working to advance research to better diagnose, manage, and cure MDS and related diseases. But it can be challenging to create awareness and fundraise for research.“Partof what we do at the foundation is to educate peo ple on awareness of the dis ease, just the simple fact that MDS exists,” said Tracey Iraca, Executive Director, MDS Foundation, Inc. “It can be really frustrating for a patient when you’re diagnosed with a disease you’ve never heard of, that then you go out, and no one you know has heard of it either.“It’s difficult for the patient but it’s also difficult for advo cacy organizations. It’s tough to fundraise for, it’s tough to

Myelodysplastic syndromes (MDS) are often referred to as bone marrow failure disorders.

The unrecognized and under-diagnosed condition occurs when bone marrow doesn’t produce enough healthy blood cells.

Why6

Foundations and Advocacy Work Are Important to Patients With MDS

People with MDS often have low blood cell counts

and often experience anemia, infection, spontaneous bleed ing, or easy bruising.

Treatment

MDS is also known as a form of blood cancer.Healthy bone marrow produces imma ture blood cells that develop into mature red blood cells, white blood cells and platelets. But in people with MDS, the cells may not mature and they may accumulate in the bone marrow. The end result is that the patient has fewer than normal mature blood cells.The condition, which pri marily affects people over age 65, can affect younger people, too.MDS is not necessarily fatal because it’s a gradual process. But some patients die as a result of the effects of the dis ease, including reduced blood cells and the body’s loss of the ability to fight infections and controlAboutbleeding.30%of people diag

There’s no cure for MDS. Three treatments are currently available to treat symptoms and slow the progression of the disease. A stem cell trans plant is considered the only potential cure. The average survival rate for low-risk patients who don’t receive a transplant is six years. However, high-risk patients have a survival rate of only five months.

For over 25 years, the MDS Foundation, a global nonprofit advocacy organization, has been supporting patients with MDS and their families, as

nosed with MDS will progress to AML, acute myeloid leuke mia, a fast-growing cancer where too many immature white blood cell are found in the blood and bone marrow.

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Doctors may dismiss symptoms as just being part of aging, but since the median age of people with MDS is 70, patients need to be aware of the condition and be their own advocate and seek out an advocacy organization for support.“Find an organization that specializes in your disease to learn more and to get help walking through the process of your disease,” Iraca said. n

support when you don’t have that general public knowledge of your disease,” Iraca said. Iraca encourages patients who are anemic or feeling fatigued to examine their lab work, and if any blood counts are off, to ask their doctor to take a deeper look.

Kristen Castillo

MDS is not inherited and it’s not contagious. Still, the causes are unknown. While some people are thought to be born with a tendency to develop the condition, known as primary MDS, others develop it after radiation and chemotherapy treatments for cancer. This is known as sec ondary MDS.

MDS can be challenging.

N r r r 1 F H r-r k r r fr x r 2 COULD FOCUSING ON MACROPHAGES AND PHAGOCYTIC SIGNALS LEAD TO CLUES ABOUT HIGHER-RISK MDS? GILEAD and the GILEAD Logo are trademarks of Gilead Sciences, Inc. © 2022 Gilead Sciences, Inc. All rights reserved. US-UNBP-1213 08/22 References:1. Chao MP, Takimoto CH, Feng DD, et al. Front Oncol. 2020;9:1380. doi:10.3389/fonc.2019.01380 2. Yamauchi T, Moroishi T. Cells. 2019;8(5):398. doi:10.3390/cells8050398

about 25-30% of patients, we are seeing response rates with CAR T-cell therapy of over 90%, which is truly remarkable.

It is in the relapse setting where we have seen the great est progress in the development of new treatments, especially those considered to be “immu notherapy,” where we employ a

Foundation has a dedicated program to help overcome these disparities. The M-Power Project is designed to empower patients and communities to change this unfortunate course of myeloma.Theincreasing number of treatment options has been one of the reasons behind considerable improvements in survival rates among myeloma patients. We now use more combinations of new therapies in the frontline setting, as well as during a relapse.

multiple myeloma cells, the antibodies they produce now damage the body and can par ticularly cause bone and kid neyMultipledamage.myeloma accounts for about 2% of all cancers but is twice as common in African Americans. It has been histori cally considered incurable, but the prognosis has dramatically changed over the past 10 years — with most patients living a decade or more. However, we are aware that tremendous disparities exist in myeloma, especially in the African Amer ican community, including delayed diagnosis, reduced access to therapy, and, as a result, shortened survival.

It is an exciting year for progress toward a cure in blood cancer as dozens of drugs and therapies are being developed for multiple myeloma.

Multiple myeloma is a blood cancer that originates in the bone marrow, which is the fac tory of our blood. The specific cell that becomes cancerous is the plasma cell — the cell that makes antibodies. When you have a vaccination, or when your body is exposed to an infection, it is the plasma cell that jumps into action and pro duces antibodies (also known as immunoglobulins) to help fight that infection.

I have been a myeloma doc tor and researcher for over 25 years. I have never seen a more exciting year than 2022 for the development of new ways to conquer this awful disease. There is still so much to do, but we genuinely believe we are seeing a cure on the horizon. n

And there are dozens of other drugs and approaches being developed in myeloma.

This saves the complexity of CAR T-cell therapy by avoid ing the challenge of collecting T cells, manufacturing them, and re-infusing them in the patient.Over 10 bispecific antibodies are being developed, and we are see ing response rates in about two-thirds of the patients. This is unprecedented.

The International Myeloma

Joseph Mikhael, M.D., M.Ed., FRCPC, Chief Medical Officer, MyelomaInternationalFoundation

Lastly, the future is bright in myeloma research, and it brings hope to our patients.

When plasma cells become

The next wave of therapies will be “bispecific” antibod ies. These are drugs we give directly to patients that have two arms (hence the phrase “bi”) — one arm attaches to the myeloma cell, while the other attaches to a local T cell and immediately engages it to destroy the myeloma cell.

TreatmentsTherapiesinDevelopmentsExciting8Myelomaand READ MORE AT WWW.FUTUREOFPERSONALHEALTH.COM

patient’s own immune system to fight the myeloma. One of the most exciting forms of immunotherapy is CAR T-cell (chimeric antigen receptor) therapy. In this pro cess, we collect T cells from patients — these are like sol dier cells that are designed to attack. We then “teach” these T cells to recognize the myeloma cell by attaching to them a receptor that is specific to theFurthermore,myeloma. we multi ply them in the lab so we now have a full army of T cells primed to attach to the myeloma. We then re-infuse these cells into the patient.

Whereas prior relapse ther apies may induce response in

Not only are we seeing incredible response rates, we are also seeing that they are durable — lasting over two years in most patients. We now have two CAR T-cell products approved by the FDA, and many more on the way.

A powerful way to ight cancer lives inside your body.f

To ﬁght cancer, we are developing immunotherapies that work with the body’s natural defenses. Helping us get closer to a future where disease is a thing of the past. Learn more at www.janssen.com.

forusedbeingisandmodelscontainsdepictedimageThe 2022JGS©LLC.Services,GlobalJanssenonly.purposesillustrative

quality of life, and, ultimately, finding a cure.

Symptoms and diagnosis

Approximately 295,000 Americans have one of a rare group of blood cancers — polycythemia vera, essential thrombocythemia, or myelofibrosis — collectively known as bloodincharacterizedneoplasmsmyeloproliferative(MPN),whicharebyanincreaseredbloodcells,whitecells,orplatelets.

fatigue, muscle pain, and lack of concentration. One of his worst symptoms was itching.

Patient voices

Symptoms of MPNs, such as fatigue, bleeding or bruising, nights sweats, and itchy skin, often start months or years before diagnosis. However, symptoms are often overlooked since they may overlap with anotherDiagnosisdiagnosis.often occurs after abnormal bloodwork, such as

high or low blood counts. MPNs are typically diagnosed in men and women who are over the age 50, with most being in their 60s.With proper treatment, many people with MPN live normal life spans. However, others may experience com plications including clots and abnormal bleeding.

Kristen Castillo

In polycythemia vera (PV), there are too many red blood cells made in the bone marrow. Essential thrombocythemia (ET) occurs when the bone marrow produces too many platelets. Both PV and ET may put the patient at risk for heart attack, stroke, or pulmonary embolism.Peoplewith primary myelo fibrosis (PMF) have “fibrosis,” a buildup of scar tissue in the bone marrow, causing prob lems, such as an enlarged spleen or liver.

MPNsUnderstandingandWhat ET, PV, and MF Patients Need to Know

While MPNs are chronic and there are a few therapies avail able, there isn’t a cure. But one group — the MPN Research Foundation (MPNRF) — is on a mission to fund research toward discovering new treat ments, improving patients’

The research foundation, which has been working for 21 years to fund global innovative approaches for prevention and new therapies, has awarded over $16 million for MPN blood cancer“MPNs,research.specifically new treatment options, have become a hot topic. The prom ising news is we now have four treatments available for some MPN patients. The hopeful news is also the several treat ments in late-stage develop ment that could become avail able in the next 18-24 months,” said Kapila Viges, CEO of MPN Research Foundation. “Doctors are eager to learn about and gain experience with these drugs to have more options to offer and help patients through their journey.”

is focused on to better under stand it.”

MPNRF held an externally led, patient-focused drug development meeting with 135 in-person and web-based participants, which gave the MPN patient community an opportunity to educate Food and Drug Administration rep resentatives, biopharmaceuti cal companies, and academic researchers about the chal lenges of living with an MPN.

“In terms of prognosis, some MPN patients may progress very quickly, in a matter of a few years,” said Richard Win neker, Ph.D., head of scientific strategies for MPNRF. “Yet many patients can go decades maintaining stable health, with the uncertainty of if or when they might get worse. It’s this concept of MPN dis ease progression that MPNRF

“It was nearly body-wide pain worse than any burn I’ve ever had,” he said. “It was so bad, I was unable to fix a glass of ice water, which I thought helped, or say more than three words.”Another PV patient, Diane R., said, “I’m very worried about having another TIA or stroke. To quote my neurolo gist, ‘It’s not if but when.’”

Out of that meeting, MPNRF released the “Voice of the Patient” report. For example, David A., a 64-year-old PV patient, says his disease pro gression was marked a decade after diagnosis with increasing

On a mission

MPNRF is committed to raising awareness among all stakeholders, including patients and providers. Its website, mpnresearchfounda tion.org, is a comprehensive resource. n

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INDICATION

Colitis: Discontinue if signs or symptoms of colitis.

Ophthalmologic Toxicity: Advise patients to have eye examinations before and during treatment. Evaluate eye symptoms promptly and discontinue if new or worsening eye disorders.

Cardiovascular Toxicity: Avoid use in patients with severe, acute or unstable cardiovascular disease. Monitor patients with history of cardiovascular disorders more frequently.

Patients exhibiting the following events should be closely monitored and may require dose reduction or discontinuation of therapy: Depression and Suicide: Monitor closely for symptoms and need for Endocrinetreatment.Toxicity: Discontinue if endocrine disorders occur that cannot be medically managed.

Pulmonary Toxicity: Discontinue if pulmonary inﬁltrates or pulmonary function impairment.

Dental and Periodontal Toxicity: Advise patients on good oral hygiene and to have regular dental examinations.

Hypersensitivity Reactions: Stop treatment and immediately manage Pancreatitis:reaction.Consider discontinuation if conﬁrmed pancreatitis.

Avoid use in patients with eGFR <30 mL/min.

DRUG INTERACTIONS

bone marrow,

NCCN, National Comprehensive Cancer Network; PV, polycythemia vera. the the source of so you can address the underlying disease1

BESREMi is indicated for the treatment of adults with polycythemia vera IMPORTANT SAFETY INFORMATION

Reference: 1. Besremi. Package insert. PharmaEssentia Corporation; 2021. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.2.2022.

Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment

History or presence of active serious or untreated autoimmune Immunosuppresseddiseasetransplant recipients

Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Discontinue if severe renal impairment develops.

Driving and Operating Machinery: Advise patients to avoid driving or using machinery if they experience dizziness, somnolence, or hallucination.

Decreased Peripheral Blood Counts: Perform blood counts at baseline, every 2 weeks during titration, and at least every 3-6 months during maintenance treatment.

BESREMi, the BESREMi logo, and PharmaEssentia are registered trademarks of PharmaEssentia Corporation, and the PharmaEssentia logo is a trademark of PharmaEssentia US-BSRM-2200066Corporation.(v1.0)06/2022

Hepatotoxicity: Monitor liver enzymes and hepatic function at baseline and during treatment. Reduce dose or discontinue depending on severity.

ADVERSE REACTIONS

PV,

Ropeginterferon alfa-2b-njft (BESREMi) is a recommended option by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)2 Discover more BESREMiHCP.comat

Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping

Hyperlipidemia: Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated.

USE IN SPECIFIC POPULATIONS

Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide Hypersensitivityattempt to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi.

Patients on BESREMi who are receiving concomitant drugs which are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modiﬁcation for these concomitant drugs. Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression. Avoid use with narcotics, hypnotics or sedatives and monitor patients receiving the combination for effects of excessive CNS toxicity.

© National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed May 18, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Pregnancy: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective Lactation:contraception.Advisewomen not to breastfeed during treatment and for 8 weeks after the ﬁnal dose.

The most common adverse reactions reported in > 40% of patients in the PEGINVERA study (n=51) were inﬂuenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. In the pooled safety population (n=178), the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and inﬂuenza-like illness (11%).

Please see Brief Summary of full Prescribing Information, including Boxed Warning, on adjacent pages.

BESREMi targets

CONTRAINDICATIONStherapy.

Dermatologic Toxicity: Consider discontinuing if clinically signiﬁcant dermatologic toxicity.

WARNINGS AND PRECAUTIONS

WARNING: RISK OF SERIOUS DISORDERS

Ophthalmologic toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include severe eye disorders such as retinopathy, retinal hemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion which may result in blindness. During BESREMi therapy, 23% of patients were identified with an eye disorder. Eyes disorders ≥5% included cataract (6%) and dry eye (5%). Advise patients to have eye examinations before and during BESREMi therapy, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension. Evaluate eye symptoms promptly. Discontinue BESREMi in patients who develop new or worsening eye disorders.

5.11 Hepatotoxicity

Risk of Serious Disorders: Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy [see Warnings and Precautions (5.1, 5,2, 5.3, 5.4) and Adverse Reactions (6.1)].

5 WARNINGS AND PRECAUTIONS

Hyperlipidemia has occurred in patients treated with interferon alfa products, including BESREMi. Hyperlipidemia, hypertriglyceridemia, or dyslipidemia occurred in 3% of patients receiving BESREMi. Elevated triglycerides may result in pancreatitis [see Warnings and Precautions (5.6)]. Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated. Consider discontinuation of BESREMi in patients with persistently, markedly elevated triglycerides.

Hepatotoxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include increases in serum ALT, AST, GGT and bilirubin. BESREMi is contraindicated in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment [see Contraindications (4)]

Cardiovascular toxicity has occurred in patients receiving interferon alfa products, including BESREMi. Toxicities may include cardiomyopathy, myocardial infarction, atrial fibrillation and coronary artery ischemia [see Adverse Reactions (6.1)] Patients with a history of cardiovascular disorders should be closely monitored for cardiovascular toxicity during BESREMi therapy. Avoid use of BESREMi in patients with severe or unstable cardiovascular disease, (e.g., uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction.

Leukopenia of grade 3 (WBC counts <2,000 – 1,000/mm3) or greater occurred in 2% of BESREMi-treated patients. Infection occurred in 48% of BESREMi-treated patients, while serious infections occurred in 8% of BESREMi-treated patients. Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of infection or bleeding.

5.5 Hypersensitivity Reactions

BESREMi is contraindicated in patients with:

5.7 Colitis

5.6 Pancreatitis

• Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt

Endocrine toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include worsening hypothyroidism and hyperthyroidism. Autoimmune thyroiditis and hyperglycemia, including new onset type 1 diabetes, have been reported in patients receiving interferon alfa-2b products. Eight cases of hyperthyroidism (4.5%), seven cases of hypothyroidism (3.9%) and five cases (2.8%) of autoimmune thyroiditis/ thyroiditis occurred in the development program of BESREMi.

5.2 Endocrine Toxicity

5.8 Pulmonary Toxicity

5.9 Ophthalmologic Toxicity

BESREMi is indicated for the treatment of adults with polycythemia vera.

• Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi

5.4 Decreased Peripheral Blood Counts

Decreased peripheral blood counts have occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). Thrombocytopenia of grade 3 (platelet counts <50,000 – 25,000/mm3) or greater occurred in 2% of BESREMi-treated patients. Anemia of grade 3 (Hgb < 8 g/dL) or greater occurred in 1% of BESREMi-treated patients.

BESREMi (ropeginterferon alfa-2b-njft) injection, for subcutaneous use

BESREMi (ropeginterferon alfa-2b-njft)

Increases in serum ALT ≥3 times the upper limit of normal (ULN), AST ≥3 times the ULN, GGT ≥3 times the ULN, and bilirubin >2 times the ULN have been observed in patients treated with BESREMi.

Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease [Contraindications (4)]. Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during BESREMi therapy. Discontinue BESREMi in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi.

Hypersensitivity reactions have occurred in patients receiving interferon alfa products, including BESREMi. BESREMi is contraindicated in patients with hypersensitivity reactions to interferon products or any of the inactive ingredients in BESREMi [see Contraindications (4)]. Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis). If such reactions occur, discontinue BESREMi and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment.

• Immunosuppressed transplant recipients

Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa products, some cases occurring as early as 12 weeks after start of treatment. Symptoms may include abdominal pain, bloody diarrhea, and fever. Discontinue BESREMi in patients who develop these signs or symptoms. Colitis may resolve within 1 to 3 weeks of stopping treatment

In the clinical development program of BESREMi, 36 patients (20%) experienced liver enzyme elevations, 33 of whom had elevations of 1.25-5x ULN. Patients were able to resume BESREMi upon resolution of liver enzyme elevations. Liver enzyme elevations have also been reported in patients after long-term BESREMi Monitortherapy. liver enzymes and hepatic function at baseline and during BESREMi treatment. Reduce BESREMi dosage by 50 mcg for increased AST/ALT/GGT then monitor AST/ALT/GGT weekly until the values return to baseline or grade 1 (ALT and AST < 3 x ULN if baseline was normal; 1.5 - 3 x baseline if baseline was abnormal, and GGT < 2.5 x ULN if baseline was normal; 2 - 2.5 x baseline if baseline was abnormal) [see Dosage and Administration (2.3) in

See package insert for full Prescribing Information

Pulmonary toxicity has occurred in patients receiving interferon alfa products, including BESREMi. Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis. Some events have resulted in respiratory failure or death. Discontinue BESREMi in patients who develop pulmonary infiltrates or pulmonary function impairment.

WARNING: RISK OF SERIOUS DISORDERS

• Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment

Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy.

5.10 Hyperlipidemia

4 CONTRAINDICATIONS

1 INDICATIONS AND USAGE

• History or presence of active serious or untreated autoimmune disease

Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Serious neuropsychiatric reactions have been observed in 3% of patients treated with BESREMi during the clinical development program. Among the 178 patients in the clinical development program of BESREMi, 17 cases of depression, depressive symptoms, depressed mood, and listlessness occurred. Of these seventeen cases, 3.4% of the patients recovered with temporary drug interruption and 2.8% stopped BESREMi treatment.

Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products. BESREMi is contraindicated in patients with a history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt [see Contraindications (4)].

Pancreatitis has occurred in patients receiving interferon alfa products, including BESREMi. Pancreatitis was reported in 2.2% of patients receiving BESREMi. Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever. Patients may experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. Interrupt BESREMi treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation of BESREMi in patients with confirmed pancreatitis.

5.3 Cardiovascular Toxicity

5.1 Depression and Suicide

Brief Summary of Prescribing Information for

• Endocrine Toxicity [see Warnings and Precautions (5.2)]

Vertigo

e Includes headache, migraine, and head pain.

Fatigue b 47

6 ADVERSE REACTIONS

Transaminase elevations m

BESREMi may impact the ability to drive and use machinery. Patients should not drive or use heavy machinery until they know how BESREMi affects their abilities. Patients who experience dizziness, somnolence or hallucination during BESREMi therapy should avoid driving or using machinery.

Grouped Term Definitions

Renal toxicity has occurred in patients receiving interferon alfa products, including BESREMi. During BESREMi therapy, <1% of patients were reported to develop renal impairment and <1% of patients were reported to have toxic nephropathy. Monitor serum creatinine at baseline and during therapy. Avoid use of BESREMi in patients with eGFR <30 mL/min. Discontinue BESREMi if severe renal impairment develops during treatment [see Use in Specific Populations (8.6)].

• Depression and Suicide [see Warnings and Precautions (5.1)]

• Colitis [see Warnings and Precautions (5.7)]

• Embryo-Fetal Toxicity [see Warnings and Precautions (5.16)]

Upper respiratory tract infection g 27

Pruritus 45

b Includes asthenia, malaise, and fatigue.

5.16 Embryo-Fetal Toxicity

The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of polycythemia vera in 51 patients in the PEGINVERA study [see Clinical Studies (14) in the full prescribing information].

Leukopenia

Edema j

The pooled safety population described in the Warnings and Precautions section reflects exposure to BESREMi as monotherapy for the treatment of polycythemia vera dosed every two to four weeks in 178 patients in two open-label trials [PEGINVERA, PROUD/CONTINUATION PV]. The mean age at baseline was 58.6 years (range 30-85 years), 88 (49.4%) women, 90 (50.6%) men, 177 (99%)

• Renal Toxicity [see Warnings and Precautions (5.12)]

Depression

Sleep disorder i

• Ophthalmologic Toxicity [see Warnings and Precautions (5.9)]

• Dental and Periodontal Toxicity [see Warnings and Precautions (5.13)]

• Cardiovascular Toxicity [see Warnings and Precautions (5.3)]

5.13 Dental and Periodontal Toxicity

• Pancreatitis [see Warnings and Precautions (5.6)]

• Hyperlipidemia [see Warnings and Precautions (5.10)]

Among the 51 patients receiving BESREMi, 71% were exposed for 12 months or longer, 63% were exposed for three years or longer, and 53% were exposed for greater than five years.

liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).

Urinary tract infection

Dental and periodontal toxicities may occur in patients receiving interferon alfa products, including BESREMi. These toxicities may include dental and periodontal disorders, which may lead to loss of teeth. In addition, dry mouth could have a damaging effect on teeth and oral mucous membranes during long-term treatment with BESREMi. Patients should have good oral hygiene and regular dental examinations.

Adverse reactions requiring permanent discontinuation in >2% of patients who received BESREMi included depression (8%) arthralgia (4%), fatigue (4%), and general physical health deterioration (4%) In the PEGINVERA study, patients were not pre-screened for depression or anxiety disorders.

Nausea

6.1 Clinical Trials Experience

Serious adverse reactions were reported in 16% of patients in the PEGINVERA study. The most common serious adverse reactions observed during the study (≥ 4%) included urinary tract infection (8%), transient ischemic attack (6%) and depression (4%).

*Adverse Reactions defined as all treatment emergent adverse events

a Includes pyrexia, chills, and influenza-like illness.

Dermatologic toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities have included skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, and hyperhidrosis. Consider discontinuation of BESREMi if clinically significant dermatologic toxicity occurs.

the full prescribing information]. If toxicity does not improve, continue decreasing the BESREMi dose at biweekly intervals until recovery to grade 1. Hold if AST/ALT/GGT > 20 x ULN and consider permanent discontinuation if increased liver enzyme levels persist after four dose-reductions. Discontinue BESREMi in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage) during treatment [see Use in Specific Populations (8.7)].

Influenza-like illness a 59

Rash l

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

• Hepatotoxicity [see Warnings and Precautions (5.11)]

f Includes night sweats and hyperhidrosis.

c Includes pharyngitis and nasopharyngitis.

Arthralgia 47

5.12 Renal Toxicity

• Hypersensitivity Reactions [see Warnings and Precautions (5.5)]

Local administration site reactions

Thrombocytopenia

• Driving and Operating Machinery [see Warnings and Precautions (5.15)]

• Dermatologic Toxicity [see Warnings and Precautions (5.14)]

• Pulmonary Toxicity [see Warnings and Precautions (5.8)]

Table 2 Adverse Reactions in > 10% of Subjects with Polycythemia Vera in the PEGINVERA Study Over 7.5 Years.

Diarrhea

d Includes musculoskeletal pain, back pain, pain in extremity, bone pain, flank pain, and spinal pain.

Abdominal pain h

Decreased appetite

Muscle spasms

The following clinically significant adverse reactions are described elsewhere in the labeling.

Caucasian and 1 (1%) Asian. Among 178 patients who received BESREMi, 80% were exposed for 12 months or longer. The mean dose of BESREMi was 334 mcg SD ± 121 during the treatment period. In this pooled safety population, the most common adverse reactions greater than 10%, were

5.14 Dermatologic Toxicity

5.15 Driving and Operating Machinery

Nasopharyngitis c 43 Musculoskeletal pain d 41 Headache e

• Decreased Peripheral Blood Counts [see Warnings and Precautions (5.4)]

The most common adverse reactions reported in ≥10% of patients in the PEGINVERA study are listed in Table 2.

Alopecia

Hypertension k

Based on the mechanism of action, BESREMi can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) in the full prescribing information and Use in Specific Populations (8.1)]. Pregnancy testing is recommended in females of reproductive potential prior to treatment with BESREMi. Advise females of reproductive potential to use an effective method of contraception during treatment with BESREMi and for at least 8 weeks after the final dose [see Dosage and Administration (2.1) in the full prescribing information and Use in Specific Populations (8.1, 8.3)].

Adverse Reactions*

BESREMiN=51%

Neutropenia

Hyperhidrosis f 29

Dizziness

6.2 Immunogenicity

Pregnancy Testing

Infertility Females

Increased liver enzyme levels have been observed in patients treated with BESREMi. When the increase in liver enzyme levels is progressive and persistent, reduce the dose of BESREMi. If the increase in liver enzymes is progressive and clinically significant despite dose-reduction, or if there is evidence of hepatic impairment (Child-Pugh B or C), discontinue BESREMi [see Dosage and Administration (2.2) in the full prescribing information and Warnings and Precautions (5.11)].

8.4 Pediatric Use

8.1 Pregnancy

i Includes insomnia, sleep disorder, and abnormal dreams.

There are no data on the presence of BESREMi in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from BESREMi, advise women not to breastfeed during treatment and for 8 weeks after the final dose.

No dose adjustment is necessary in patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min [see Clinical Pharmacology (12.3) in the full prescribing information]. Avoid use of BESREMi in patients with eGFR <30 mL/min [see Warnings and Precautions (5.12)].

k Includes hypertension and hypertensive crisis.

Clinically relevant adverse reactions in < 10% of patients include: Cardiovascular System: Atrial fibrillation

m Includes transaminase increase, hepatic enzyme increase, GGT increase, AST increase, and ALT increase.

Concomitant use of BESREMi and narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity [see Warnings and Precautions (5.1)].

j Includes peripheral edema and generalized edema.

The incidence of binding antibodies to ropeginterferon alfa-2b-njft was 1.4% (2/146) and they were observed as early as 8 weeks post-dosing. Among the patients who tested positive for binding antibodies, none developed neutralizing antibodies.

Untreated polycythemia vera during pregnancy is associated with adverse maternal outcomes such as thrombosis and hemorrhage. Adverse pregnancy outcomes associated with polycythemia vera include increased risk for miscarriage.

Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates [see Clinical Pharmacology (12.3) in the full prescribing information]. Therefore, patients on BESREMi who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs.

Contraception Females

Concomitant use of BESREMi and myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression [see Warnings and Precautions (5.4)].

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other interferon alfa-2b products may be misleading.

Safety and effectiveness in pediatric patients have not been established.

8.7 Hepatic Impairment

7.3 Narcotics, Hypnotics or Sedatives

7.2 Myelosuppressive Agents

g Includes upper respiratory tract infection, rhinitis, bronchitis, and respiratory tract infection.

BESREMi may cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

8.6 Renal Impairment

h Includes abdominal pain upper, abdominal pain lower, and abdominal pain.

10 OVERDOSAGE

Overdosage of BESREMi may result in influenza-like symptoms or other adverse reactions. There is no antidote to BESREMi overdosage. In case of an overdose, frequently monitor signs and symptoms for adverse reactions.

Clinical studies of BESREMi did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy.

Disease-Associated Maternal and/or Embryo-Fetal Risk

8.2 Lactation

8 USE IN SPECIFIC POPULATIONS

8.3 Females and Males of Reproductive Potential

8.5 Geriatric Use

BESREMi is contraindicated in patients with hepatic impairment (Child-Pugh B or C) [see Contraindications (4)].

Manufactured 35PharmaEssentiaDistributedU.S.Nangang2F-5PharmaEssentiaby:CorporationNo.3YuanQuStreetDist.Taipei,TaiwanLicensenumber2155by:USACorporationCorporateDr,Suite325,Burlington, MA 01803, USA © PharmaEssentia USA Corporation, 2021 US-BSRM-2200063

l Includes rash, maculopapular rash, and pruritic rash.

Pregnancy testing prior to BESREMi treatment is recommended for females of reproductive potential.

7.1 Drugs Metabolized by Cytochrome P450

Clinical Considerations

Based on its mechanism of action, BESREMi can cause disruption of the menstrual cycle [see Clinical Pharmacology (12.1) in the full prescribing information]. No animal fertility studies have been conducted with BESREMi.

Risk AvailableSummaryhuman data with BESREMi use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal studies assessing reproductive toxicity of BESREMi have not been conducted. Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy (see Clinical Considerations). Advise pregnant women of the potential risk to a Thefetus.estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2-4% and 15-20%, respectively.

7 DRUG INTERACTIONS

Advise female patients of reproductive potential to use effective contraception during treatment with BESREMi and for at least 8 weeks after the final dose.

#1 neoplasmsMyeloproliferative(MPNs)

are a closely related group of progressive blood cancers in which the bone marrow typ ically overproduces one of the mature blood elements. Other shared features include ten dencies toward blood clotting and bleeding, organ enlarge ment, bone marrow scarring (fibrosis), and a possibility of transformation. Although MPNs can strike anyone at any age, most patients are afflicted in the sixth decade of life or later. Polycythemia vera and essential thrombocythemia are often found during routine bloodwork. It’s common for patients to have no symptoms or mild symptoms for years.

to human clinical trials and ultimately require approval by a regulatory agency, such as the U.S. Food and Drug Administration.

7 Things You

Didn’t Know About MPNs

idly, many people living with an MPN find clinical trials offer a better treatment option

MEDIAPLANET 15

Stem cell trans plants may offer a cure for some myelofibrosis sufferers, but there are no known cures for most MPNs. However, patients can experi

#3 Bringing new treatments to MPN patients takes many years, from discovery in the lab to pre-clinical research that tests for safety and effective ness. Successful pre-clinical therapeutic candidates move

for their disease symptoms, either after current thera pies failed or were not fully effective. Talk to your doctor about MPN trials you might qualify for, then ask questions and consider your personal options.

MPN research is rapidly acceler ating our understanding of what causes these chronic dis eases and how to treat them. While only a few MPN drug treatments are now approved, hundreds of clinical trials are underway across the globe, studying potential new and better treatment options. An MPN specialist can help you explore your eligibility to par ticipate in one or more trials. n

Ruth Fein Revell, The MPN Research Foundation

ence few or no symptoms for extended periods of time and many people who suffer from MPNs can enjoy longevity with proper monitoring and treatment. The identifica tion of the JAK2 gene marker in 2005 and the CALR gene marker in 2013 have led to significant advances in the diagnosis, understanding of

disease processes, and treat ment of MPNs.

#4 With advancingresearchsorap

#6 Because MPNs are rare, the challenge of finding enough people with ET, PV, and MF who are will ing and able to participate in a clinical trial can slow new drug approvals. “My life-alter ing symptoms have nearly dis appeared since starting a drug combination in a clinical trial. The drugs I’m on would not be available to me otherwise,” a 64-year-old MF patient said. Ask your doctor what MPN trial might be a good match for you.

A group of related blood cancers can occur in anyone at any age, so it is important to understand the symptoms and treatments of these diseases.

MPN clinical trials have gone beyond JAK inhibitors and are now looking at new targets and therapeutic pathways that will expand the universe of options for patients. This is especially promising for patients who could not tol erate JAK inhibitors or they stopped working.