Rare Diseases

A Mediaplanet Guide to Rare Disease Research, Therapies, and Advocacy

Rare Diseases

William Flaherty The skier with a rare immune disorder talks about his journey to the Olympics as a bone marrow transplant survivor

How one company is creating therapies for two rare diseases Why rare diseases can hurt families financially

MARCH 2022 | FUTUREOFPERSONALHEALTH.COM

An Independent Supplement by Mediaplanet to USA Today

Building Health Equity for Rare Diseases Each year, on the last day of February, people across the country and globe celebrate Rare Disease Day, an important awareness day to build understanding of rare diseases and their impact.

W

hile each rare disease affects a small number of people, approximately 25-30 million Americans are living with one of the estimated 7,000 rare diseases. This is roughly the same number of Americans diagnosed with diabetes or asthma, yet the experience of living with a rare condition is extremely different from a common one.

The theme for Rare Disease Day 2022 is health equity, which presents an opportunity to shine a light on the challenges rare disease patients face and what we can do — individually and as a society — to help.

Everyone’s at risk Rare diseases do not discriminate and can affect people of all genders, ages, races, ethnicities, socioeconomic statuses, religions, and sexual orientations.

Regardless of any other position they hold in society, rare disease patients often find themselves @MEDIAPLANETUSA

feeling isolated and as part of a marginalized group, sidelined from a healthcare system that is not yet perfected for their position, leaving them at a medical disadvantage.

There are urgent needs for treatment, research, and improved diagnostics. Only a few hundred rare diseases have an FDA-approved treatment, few specialists exist for each condition, and patients wait seven years, on average, for a correct diagnosis. Gaps that exist in the healthcare system are often worsened in the rare disease community, and marginalized groups may face extra barriers to care and are underrepresented in clinical trials.

Confronted with these challenges, what would health equity look like for people living with rare diseases and how can we achieve it?

Health equity will be possible by finding solutions to the disparities that exist and will be measured by results that make a difference to patients, @FUTUREOFPERSONALHEALTH

Lisa Phelps Sarfaty, M.P.H. Vice President of Community Engagement, National Organization for Rare Disorders (NORD)

including the availability of treatments, early diagnoses, improved understanding of rare diseases among medical professionals and the public, and bipartisan policies that support every single rare disease patient.

These goals require action, and there are things each of us can do — for Rare Disease Day and throughout the year — to make a difference.

Be an advocate Rare Disease Day has grown to become a movement complete with awareness events, legislative meetings, school programs, and medical training around the country, often span-

ning weeks at a time. This level of community engagement shows how much stronger we are when we work together.

Keep the momentum going and organize events in your community, attend virtual events around the country, take part in advocacy campaigns, and speak up for policies that help patients and stand against those that hinder progress.

Share your story Each person’s experience matters, and we encourage every patient, caregiver, friend, family member, teacher, colleague, doctor, nurse, researcher, and anyone touched by a rare disease to share their experience.

Increased information about living with a rare disease helps advocates and researchers target their efforts.

Support increased access Before the pandemic, most healthcare was provided in person. Frequent doctor visits

and participation in clinical trials have long resulted in costly travel, and missed work and school for rare disease patients and their caregivers.

Help ensure rare disease patients can receive the best care and quality of life with permanent expanded access to telehealth options. Check if there is a NORD Rare Disease Center of Excellence near you, or if a medical center in your community is eligible to join this national network to promote knowledge sharing, and supply more consistent and equitable care for rare diseases around the country.

The rare disease journey is not an easy one, but there are more reasons to believe in progress than ever before. We hope every American will find an opportunity to learn about the realities of rare diseases and be moved to help create a better future that gets rid of disparities by advancing science, public policy, and access to care. n

INQUIRIES: US.EDITORIAL@MEDIAPLANET.COM AND US.ADVERTISE@MEDIAPLANET.COM

PLEASE RECYCLE

Publisher Shannon Ruggiero Managing Director Jordan Hernandez Lead Designer Kayla Mendez Designer Keziah Makoundou Lead Editor Jon Adams Copy Editor Dustin Brennan Director of Content and Production Jordan Hernandez Cover Photo Tania Coffey All photos are credited to Getty Images unless otherwise specified. This section was created by Mediaplanet and did not involve USA Today.

2

READ MORE AT FUTUREOFPERSONALHEALTH.COM

MEDIAPLANET

Translating real patient needs into real-world treatments.

At CHOC, we know that research can lead to lifesaving decisions. A key part of our vision is to address a critical need in rare disease research, so every child can live the healthiest life possible.

Finding the answers that each child needs to thrive Start With One Child. This is one of our guiding principles as we seek the answers for each child to thrive. Our “bedside-to-bedside” approach to research means we learn from every child and when we know the answer for one, we can extrapolate to find the answer for many.

With more than 530 active studies in over 30 specialties, CHOC is committed to personalized, precision-medicine research for the neonatal, pediatric, adolescent, and young adult populations.

A destination for kids with rare conditions Kids from around the world come to CHOC for treatment of their rare conditions. We are the largest center in the United States, and second largest in the world, for Brineura treatment for kids with CLN2-associated Batten disease, a neurological disorder that leads to blindness, loss of ability to speak or move, dementia, and death.

CHOC is on track to become an active site for a gene therapy clinical trial to give brain cells the ability to produce the missing enzyme that causes Batten disease.

Success in rapidly diagnosing genetic diseases In the last four years, CHOC has ordered the comprehensive and cutting-edge test of rapid whole genome sequencing (rWGS) on 150 patients, with more than half of them getting a precise diagnosis that, in many cases, has resulted in life-changing care.

• rWGS can identify the cause of rare diseases in a manner of days, leading to faster, more customized treatments.

• This level of early intervention can eliminate the need for further tests, reduce costs and save lives in the short and long term.

READ STORIES OF INNOVATIVE RESEARCH choc.org/research-usatoday

The Uncommon Cause of Rare Disease

The pandemic has focused a white-hot spotlight on health disparities, particularly those related to COVID-19.

Still largely hidden from public view, however, are the challenges facing minoritized communities living with rare diseases.

No matter what race, culture, or background you come from, if you have a rare disease, you are already underserved. Rare diseases collectively affect more than 400 million people worldwide (that’s about the number of people estimated

4

to have had COVID-19). Yet for more than 95 percent of the hundreds of millions living with rare diseases, there are no vaccines, no approved treatments, and no globally funded and orchestrated efforts to urgently find cures.

More than 80 percent of rare conditions have a genetic basis, so people with rare diseases typically couldn’t have done anything to avoid having one. More than half of the rare disease population is made up of children, and nearly a third of those children will die by the age of 5.

It takes five to seven years on average to get a diagnosis for

READ MORE AT FUTUREOFPERSONALHEALTH.COM

a rare disease — literally more than a lifetime for some. Adolescents and adults often face severe, debilitating, or deadly impacts from rare diseases. In the absence of approved medicines, the cost of hospitalization and other interventions associated with rare diseases was estimated to be nearly a trillion dollars in the United States alone in 2019.

Lack of access Now consider the plight of rare disease patients and families from communities that are already disproportionately disadvantaged in our healthcare

system. The lack of access to screenings, genetic testing, and medical specialists can further extend the diagnostic odyssey, leading to even worse outcomes and greater suffering. The financial hardships associated with rare diseases — which extend well beyond medical costs — can also be crippling.

The difficulties of diagnosing and reaching patients with rare diseases from minoritized communities can also lead to significant under-representation in clinical trials, which quite often is the only hope for treating a rare condition.

Investment in research and drug development for rare diseases that disproportionately impact minoritized populations has also lagged, further diminishing prospects for access to effective treatments.

Improving equity In 2021, Global Genes partnered with the Rare Disease Diversity Coalition (RDDC) to help address problems and find solutions for critical challenges that those in minoritized communities face. This partnership included a summit in November that brought together stakeholders to explore and identify actionable takeaways for partners across the rare disease community. These discussions and related outputs were captured in a report released in early March.

As a next step, the partnership will launch a campaign to reach communities of color with a focus on discovering and learning about one’s family medical history. This has been identified as a glaring yet common gap in BIPOC communities, lengthening time to correct diagnoses and appropriate treatments.

As more resources and programs become available for already underserved rare disease patients and families, we need to ensure these advancements are inclusive of and equitably accessible to minoritized populations within the rare disease community.

Finally, we need to make our collective voices heard in unison so addressing unmet needs across all populations living with rare diseases becomes the public health priority it deserves to be. n Craig Martin, CEO, Global Genes

SPONSORED

Bridging the Gap Between Pediatric and Adult Sickle Cell Care

André Harris is a social work PhD student from Houston and a passionate advocate for young people with sickle cell disease (SCD). He knows all too well how hard it is to be a teen living with SCD. “I grew up in a single-parent home and my mother had to work. As a child, I had to learn about my SCD and how to navigate not only the healthcare system but the systems of transportation and social services by myself so that my mother could provide for us.”

Life is already overwhelming with the transition into adulthood, but it’s made more challenging with a disease that can cut life tragically short. The average life expectancy for those living with SCD remains up to 30 years lower than that of the average American.1 SCD is a genetic blood disorder more common among Black and Hispanic

Americans.2 From birth, the disease sets out to deform and destroy red blood cells, causing excruciating pain during an attack (known as a “pain crisis”), and if left untreated, organ failure and death. The CDC estimates that 100,000 Americans are affected by the disease.2 Within the U.S. healthcare system, SCD exposes the painful vulnerability of its minority and low-income affected individuals, with these inequalities amplifying as children transition to adulthood. Though great strides have been made to reduce pediatric mortality and morbidity in SCD, the period of transition leads to significant care gaps, and sadly is often marked by increased hospitalizations and mortality.

“SCD patients need healthcare to be more supportive between ages 16 and 30. It’s the most vulnerable time in their life.” says Dr. Ifeyinwa Osunkwo, M.D., MPH, Forma’s chief patient officer and senior vice president. “Even with good

care, it’s still hard. Without good care, it’s devastating.”

Transition is an important next step in the life of teens living with SCD. It is the process culminating in the point at which a patient (usually age 18) must move from the warm, protective arms of pediatric care to adult care. It comes at a critical time as young people are poised to navigate the complexities of new healthcare systems, and insurance changes with an increased focus on education or employment — while simultaneously managing their disease. There is also the dark shadow of systemic racism, unconscious bias, and the stigma of the disease to contend with, impeding prompt and ongoing access to appropriate care.3 ”As sickle cell providers, you need to prepare a patient, try and reassess the gaps that this patient may have so that when they do get to the adult side, they’re successful,” says Nirmish

Lubeck et al., 2019; Piel et al., 2017.

Centers for Disease Control and Prevention. (2019, October 21). Sickle

cell disease (SCD). Retrieved from link. 3Power-Hays A, McGann PT. When actions speak louder than words—

racism and sickle cell disease. New England Journal of Medicine. 2020 Nov 12;383(20):1902-3. 4 2021 Forma

1

2

Shah, M.D., associate professor in the division of hematology at Duke University and director of their sickle cell transition program.

Both Harris and Shah have partnered with formabridge — an initiative

by Forma Therapeutics, a clinical-stage biopharmaceutical company — to help SCD patients navigate the complexities of managing their transition.

Within this program, Forma launched a comprehensive online resource, www.formabridge.com, curating available information and tools for the SCD community to help patients and their caregivers prepare for and successfully transition into adult care.

According to the Forma SCD Trend Report: The State of Transition, the top patient challenges during transition include suboptimal support in moving to an adult provider, lack of mental health support, and limited availability of disease information. Many patient respondents indicated the transition conversation did not start until 17, well beyond the recommended age of 12, meaning patients aren’t properly prepared.4 “If there’s one thing for a patient to understand about improving the transition process, it would be to know everything they can about themselves and their disease. By understanding their disease, they understand what’s coming, and how to prepare.” says Dr. Shah.

Through the creation of formabridge, Forma commits to working with the community to empower and support young adults living with SCD so that no one is lost in transition. n formabridge

For more information on SCD transition, please visit formabridge.com

Sickle Cell Disease Trend Report: The State of Transition, 1st ed., Watertown, MA, Forma Therapeutics, 2021.

MEDIAPLANET

5

Why It’s an Exciting Time in Rare Disease Drug Development Experts from the World Orphan Drug Congress USA 2022 discuss the factors enabling better research and development of rare disease drugs, and what can be done to improve the field in the future.

Janet Woodcock, M.D. Principal Deputy Commissioner, U.S. Food and Drug Administration

Why does it take more than six years for the average rare disease to be diagnosed?

Janet Woodcock: Medicine still relies a lot on the “see one, do one, teach one” paradigm. If you’ve never seen one diagnosed, you probably won’t recognize one when you do see it.

We need to use more information technology in diagnosis, not just rely on standard diagnostics — they often don’t reveal the rare disorder.

Peter Saltonstall: Every family’s rare story is unique. There are costs associated with every step of the long diagnostic odyssey, from accessing resources for testing, to finding a specialist, to recognizing and considering a rare disease, to receiving authorization for insurance coverage for testing. It is often symptoms that are being treated initially, as opposed to the underlying cause.

What is the most important medical advancement in rare diseases in the past five years?

Suneet Varma: With more than 7,000 known rare diseases, this is an area of immense complexity. Recent 8

Peter Saltonstall President and CEO, NORD

breakthroughs have allowed for better understanding of the underlying drivers of many rare diseases, 80 percent of which have genetic origins.

This has led to the development of highly targeted investigational treatments with potential to provide a transformational clinical benefit, one example being gene therapy.

PS: In 2012, the FDA set up the PatientFocused Drug Development (PFDD) initiative to obtain and integrate the patient perspective on rare diseases, treatments, and outcomes. While not explicitly a medical advancement, I believe the most important display of growth in the rare disease field as of late has been the re-emphasis on the patient; accessing their natural history data, sharing and learning their stories, and engaging their participation in PFDDs, clinical trials, and drug development.

How can we make rare disease drug development more equitable?

JW: Most drug development is done by for-profit companies. They have to stay in business, so they need to have successful programs and get a return on investment. The FDA runs incentive

READ MORE AT FUTUREOFPERSONALHEALTH.COM

Suneet Varma Global President, Rare Disease, Pfizer

programs like Orphan Drug exclusivity to sweeten the pot, and we also give out grants to help with development costs.

Patient groups that help stake development costs have been successful in some diseases. The FDA works with patient groups to develop knowledge about the disease, its progression, and the kinds of problems it causes, and this can give developers a head start on their programs, incentivize investment, and potentially create more competition in the field.

SV: Clinical trials must be representative of those most impacted by a disease, and inclusive of communities that have, unfortunately, historically been underserved. This is particularly important for rare diseases, many of which disproportionately impact communities of color. Progress has been made, but much more work is needed.

What do you think is most exciting about the future of rare disease drug development?

JW: The new tools that are on the horizon — gene therapies, cellular therapies, gene editing technologies — will let us attack the causes of many

rare diseases in ways we couldn’t even imagine previously. These tools could help us treat the causes of diseases rather than just reducing the symptoms, bringing people longer and healthier lives.

PS: Telehealth and improving patient access to care. The field of digital health has changed rapidly as of late, and we must ride that wave to combat the barriers that have arisen, including bridging the digital divide and providing credible and high-quality patient data.

SV: Currently, only 5 percent of rare diseases have an FDA-approved treatment. Thankfully, we are seeing a tremendous increase in the number of clinical trials that seek to address this significant unmet need. This is coupled with an unprecedented opportunity to leverage lessons learned from the COVID-19 pandemic to expedite drug development without compromising safety.

I’m excited about the potential to apply the same sense of urgency to rare disease drug development; from research and clinical development, to regulatory reviews and approvals, to manufacturing, and ultimately, delivering breakthroughs to patients. n MEDIAPLANET

We remain committed to bringing innovative treatments for people living with rare diseases We believe that mRNA therapeutics will target the root cause of many rare diseases and change the future course of treatments

Our rare disease pipeline includes clinical and preclinical programs for ornithine transcarbamylase (OTC) deficiency and cystic fibrosis, respectively, as well as multiple partnered programs.

For more information visit: ArcturusRx.com

New data is shedding light on a public health crisis — the cost of suffering from a rare disease. ““What is the cost of rare disease to you?”

We posed this question to the national rare disease community — patients and caregivers — while conducting the recent National Economic Burden of Rare Disease Study, the most comprehensive assessment of the total cost of rare diseases in the United States to date. The answer? In 2019 alone, the cost was nearly $1 trillion for just 379 rare diseases.

This estimate surpasses the economic impact estimated for many of the costliest chronic diseases described by the Centers for Disease Control and Prevention (CDC), including diabetes, heart disease, and cancer. To generate the data for this study, we identified both direct medical costs, via an analysis of claims data, and indirect and non-medical costs, via a survey of 1,399 members of the rare disease community.

But it wasn’t the overall findings that were the most breathtaking. The data revealed indirect and non-medical costs — costs absorbed directly by families — to be the highest driver at $548 billion.

The data is growing Since our findings were released, three more studies from a variety of authors have been published which shed new light on the collective economic cost impacts of rare diseases, disorders, and conditions that affect between 25 to 30 million people in the United States. While each study was constructed differently, significant commonalities exist between them in terms of certain data sources, approaches, and, most importantly, conclusions.

We joined key stakeholders from the studies to identify specific and actionable solutions that can, if implemented, more fully capture the complete medical and economic impacts of rare diseases and improve our ability to meet the needs of this population.

Find out more about the policies impacting the rare disease community and how to take action at EveryLifeFoundation.org.

Annie Kennedy, Chief of Policy, Advocacy, and Patient Engagement, EveryLife Foundation for Rare Diseases

When William Flaherty was diagnosed with HLH at 3 years old, he was given a 10 percent chance to live. Now he’s competing for Olympic gold.

William Flaherty competed in both the men’s slalom and giant slalom at the 2022 Winter Olympics in Beijing, where he notched the third-best finish ever for a Puerto Rican athlete in the Winter Olympics.

But Flaherty’s road to success began with a major hurdle: when he was 3 years old, he was diagnosed with hemophagocytic lymphohistiocytosis (HLH), a rare disease with a very low survival rate.

The worst moments “It was December 31st of 2007,” Ann Flaherty, William’s mother, remembered, “and I saw some yellow in the corners of his eyes.”

As a pediatric nurse, Ann knew William’s symptoms meant he likely had liver problems and that she had to act fast.

“We got two potential diagnoses in one night; one of leukemia and one of liver failure,” Ann said. “Right away, they’re asking, ‘Does he have a sibling? Where can we get a liver?’ Basically, he was in the hospital for a week before we got a proper diagnosis.”

When the diagnosis was narrowed down to leukemia or HLH, the doctors told William’s parents to “Pray for cancer.”

“They said, ‘Don’t Google HLH, you’re not going to like what you see,’” Ann said. “Pray for leukemia, because leukemia had at that time an 85 percent cure rate, but HLH had a 10 percent cure rate.”

Hoping for the best William’s doctors outlined a plan. First, they would put

10 READ MORE AT FUTUREOFPERSONALHEALTH.COM

PHOTO TANIA COFFEY

Olympian William Flaherty’s Early Battle With a Rare Disease

The Economic Impact of Rare Disease

him on steroids and give him a round of chemotherapy, and if that didn’t work, they would need to perform a bone marrow transplant.

“Through the whole process, he was a happy kid,” Ann said. “But about two days after they started chemo, he started vomiting and couldn’t keep anything down. We had to put a feeding tube up his nose.

That was the only time we broke his spirit.”

After the chemotherapy treatment didn’t work, William’s parents had to seriously consider a bone marrow transplant. Luckily, William’s brother Charles was a 100 percent match. William’s bone marrow transplant was a success, but the chemotherapy treatment still impacts his life today.

Advocacy William’s father Dennis, who recently passed away, became a huge advocate for rare disease awareness after William’s transplant.

“The first thing he did was set up the Center of Excellence at Cincinnati Children’s Hospital,” Ann said. “We did a ton of outreach and started a conference that ran for probably 10 years at Cincinnati Children’s.

We would invite doctors from all over the world and pay for their flights and their housing for them to come for a weekend and learn all about HLH.” At 17 years old, William is able to live an active life.

He’s also able to keep up with his studies anywhere in the world thanks to Laurel Springs School, an online school.

“Laurel Springs has helped me significantly,” he said, with Ann adding that “It’s given us the flexibility to travel whenever we need to.” n Ross Elliott

Why the Future Looks Bright for Geneticists and Their Patients The American College of Medical Genetics and Genomics (ACMG) provides the resources, advocacy, outreach, and education necessary to help medical geneticists identify and treat genetic diseases; those that result from a mutation that affects one’s genes.

It wasn’t long ago that doctors had few, if any, therapies to offer patients who presented with rare genetic disorders. But a lot has changed in the past couple of decades.

“In my own career, when I started training 20 or so years ago, there were very few therapies available for rare genetic diseases,” said Dr. Brett Graham, M.D., Ph.D., an associate professor in the Department of Medical and Molecular Genetics at the Indiana University School of Medicine. “And now, there’s just so many more.”

Know thy enemy One of the key reasons research into genetic diseases has come so far over the past few decades is the Human Genome Project, a collaborative scientific effort (that was finished in 2003) in which

the entire human genome was mapped and sequenced.

“That gave us for the first time, at least in theory, the ability to understand everything about the genetics of our bodies,” said Dr. Jerry Vockley, M.D., Ph.D., a professor in the Department of Pediatrics at the University of Pittsburgh School of Medicine.

When Dr. Vockley graduated from the University of Pennsylvania almost 40 years ago, gene therapies were something of a far-off concept. But because the Human Genome Project introduced exome and genome sequencing as diagnostic tests, it allowed clinicians to make informed healthcare decisions for patients with these disorders, and researchers to develop more targeted therapies.

Supporting geneticists Dr. Vockley is a board member of the ACMG and Dr. Graham chairs its Therapeutics Committee. Through political advocacy, community outreach, aggregation of resources, and more, the ACMG serves as a critical resource for medical geneticists and their patients.

Because of contributions and advocacy provided by the ACMG, similar organizations, and the U.S. government, Dr. Graham says there are hundreds of clinical trials ongoing for genetic diseases, resulting in a constant flow of therapies and cures becoming approved and available. “That really is changing the face of medicine,” he said.

As the field of genetics is constantly evolving, the ACMG also aims to inspire more medically inclined professionals to pursue careers in genetics so they can further advance our understanding of and therapies for these disorders.

“With 7,000 diseases and technology that’s advancing rapidly, there aren’t enough geneticists out there,” Dr. Vockley said. “For every one person who finishes training, there are probably half a dozen jobs to fill. So, it’s one of the goals of the ACMG to get our message out to medical schools and get medical students excited about it.”

Learn more about the advocacy, support, and resources the ACMG provides by visiting ACMG.net. n

Why Genetic Testing Is the Key to Diagnosis For those with a primary immunodeficiency (PI), one of more than 450 rare conditions that affect the immune system, genetic testing holds the key to early diagnosis and appropriate treatment.

There are more than 450 types of PI, a rare, chronic, genetic disorder that affects approximately 500,000 Americans. People with PI are prone to a wide range of infections and are at increased risk of certain cancers and autoimmune disorders. It is a life-threatening and lifelong condition.

Because PI often presents in the form of infections, clinicians treat the infection while missing the underlying cause. Thousands go undiagnosed, and even for those with a diagnosis, it can take 9-14 years from the onset of symptoms to get a proper diagnosis and treatment.

Because this group of diseases is caused by defects in genes involved in the development and functioning of the immune system, genetic testing is often required to ensure an accurate diagnosis. Genetic testing may also hold the key to early diagnosis, proper treatment, and an increased understanding of the prevalence of PI. There are currently two sponsored, no-charge genetic testing programs available that include pre- and/or post-testing genetic counseling services. If you are a resident of the United States or Canada, talk to your doctor to determine if you meet the criteria to qualify for either genetic testing program.

You can learn more at primaryimmune.org/ genetic-testing.

Tammy C. Black, Vice President, Communications, Immune Deficiency Foundation

Dustin Brennan

PEOPLE WITH APDS ARE PRONE TO INFECTIONS AND OTHER CONDITIONS.

.com

Visit AllaboutAPDS.com to learn more about the signs and symptoms of APDS and eligibility for genetic testing.

Activated PI3K Delta Syndrome (APDS), a rare form of Primary Immunodeficiency

APD-US-2022-0045

MEDIAPLANET

11

Innovative Program “Drafts” Researchers To Support People Impacted

by Rare Diseases The Young Investigator Draft shines a spotlight on the critical need for rare disease research and honors emerging researchers who are making an impact.

The Uplifting Athletes Young Investigator Draft celebrates some of the best and brightest young scientists whose research will positively shape the lives of people impacted by rare diseases. On this night, science — and the impact it is having on the more than 30 million Americans affected by rare diseases — takes center stage.

This a unique event where athletes, people impacted by rare disease, scientists, life science professionals, and many others unite to cheer on these scientists, because together they believe that through science, there is a hope tomorrow will be better than today.

Uplifting Athletes teams up with rare disease patient advocacy organizations, which are formally organized communities created to support the specific needs of an individual disease population, to infuse rare disease researchers with funding to impact as many of the more than 7,000 known rare diseases as possible.

A Young Investigator Draft grant is awarded to the top researchers who apply through a joint application with a patient advocacy organization, which also cofunds the grant with Uplifting Athletes. The co-funding of these unrestricted grants doubles the money each young investigator receives, and allows them to expand the basic scientific research they are doing in order to acquire the data needed to support much larger and competitive grant proposals.

At the 2022 Draft, nine promising young investigative rare disease researchers were honored. Over the past five years, the Young Investigator Draft has grown and, after this year’s event, 34 researchers across North America have been awarded more than $620,000 in grant funding.

Andy Shay, Uplifting Athletes

12 READ MORE AT FUTUREOFPERSONALHEALTH.COM

How the Tiniest Things Can Make the Biggest Differences Small but mighty. Sometimes we forget that in this time of uncertainty and turmoil, it’s the little things that bring us the greatest comfort and lead to the most important personal and cultural breakthroughs. No one is more aware of this truth than the rare disease community.

Faced with the chronic stress of the journey of diagnosis, treatment, and often great loss, we have seen families rise to the challenge with inspirational resilience, but we have seen as many families exhausted and depleted, both physically and mentally.

The COVID-19 pandemic has exacerbated challenges and highlighted the vulnerabilities of this community. Funding has dropped off dramatically and many of the most helpful services have been interrupted. The already small social supports have been stretched and most research was put on hold at a time when the need was even greater than before.

Translational care This unique situation underscores the need for a patient-centric, Translational Care approach for disease understanding and patient support. This means the patient is the catalyst and works in conjunction with clinicians and researchers to make key observations,

develop research ideas, and find new avenues of treatment and care to explore.

Since 2008, Rare Disease Foundation (RDF) has employed this approach using a small but mighty philosophy in awarding $5,000 microgrants for rare disease research projects. Many of these small projects have grown into much larger endeavors; one in particular turned into a $2.25 million research project with a major Children’s Hospital Foundation.

All from a tiny seed of an idea and a grassroots organization supported by many small donations.

Mental health and wellness support is just as critical as research funding to the rare disease community. Rare disease patients, their families, and caregivers struggle with mental health issues, social isolation, and financial burdens.

Hope in action The good news is that mental health can be improved over the course of one’s life with the right supports in place. One major shift in healthcare as a result of the pandemic is the rise of telehealth, which reduces barriers to access.

As an example, in response to community needs during the COVID-19 pandemic, RDF developed a Mental Health and Wellness program that specifically funds counseling and related mental health supports for the rare disease community.

Even though donations were drastically reduced during the pandemic, RDF prioritized funding for the community in this way, and was able to subsidize more than 200 counseling sessions in 2020 and 2021. Due to positive participant feedback, the program received extra funding from a major donor that will allow the program to expand this year.

As we emerge from a devastating worldwide pandemic, now is the time to ramp up support for children and families navigating a rare disease diagnosis or care journey.

Technology continues to provide new innovations, and we at RDF continue to look for collaboration and strength through our rare disease community, researchers, advocates, donors, and supporters as we come together to highlight the importance of funding rare disease research and mental health support programs. n Dr. Millan Patel, M.D., Co-Founder and Chief Medical Officer, Rare Disease Foundation (RDF)

MEDIAPLANET

The first and only FDA-approved medicine for metastatic uveal melanoma

The promising potential to live longer* through KIMMTRAK Ask your doctor about a simple blood test to see if you are HLA-A*02:01 positive and determine if KIMMTRAK is right for you.

KIMMTRAK is a prescription medicine used to treat HLA-A*02:01-positive adults with uveal melanoma that cannot be removed by surgery or has spread. * KIMMTRAK was proven to extend median overall survival by 6 months in patients with metastatic uveal melanoma (21.7 months with KIMMTRAK vs 16.0 months with other treatments studied†).

Median is the middle number from all patients in the study.

Important Safety Information Including Boxed Warning What is the most important information I should know about KIMMTRAK? KIMMTRAK can cause serious side effects that can be severe or life threatening and usually happen within the first three infusions, including: • Cytokine Release Syndrome (CRS). Symptoms of CRS may include: fever, tiredness or weakness, vomiting, chills, nausea, low blood pressure, dizziness and light-headedness, headache, wheezing and trouble breathing, rash.

Tell your healthcare provider right away if you get any of these symptoms. Your healthcare provider will check for these problems during treatment with KIMMTRAK. Your healthcare provider may temporarily stop or completely stop your treatment with KIMMTRAK if you have severe side effects.

See “KIMMTRAK can cause other serious side effects” for more information.

Before receiving KIMMTRAK, tell your healthcare provider about all of your medical conditions, including if you: • are pregnant or plan to become pregnant. KIMMTRAK may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with KIMMTRAK. For females who are able to become pregnant: – Your healthcare provider should do a pregnancy test before you start treatment with KIMMTRAK. – Use an effective form of birth control during treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK. • are breastfeeding or plan to breastfeed. It is not known if KIMMTRAK passes into your breast milk. Do not breastfeed during the treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK. Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Immunocore and KIMMTRAK are registered trademarks of Immunocore Ltd. ©2022 Immunocore Ltd. All rights reserved. CM-US-TEBE-2200020 March 2022

KIMMTRAK can cause other serious side effects, including: • Skin reactions. KIMMTRAK may cause skin reactions that require treatment. Tell your healthcare provider if you get symptoms of skin reactions—such as rash, itching, or skin swelling—that are severe and do not go away.

• Abnormal liver blood tests. Your healthcare provider will do blood tests to check your liver before you start KIMMTRAK and during treatment with KIMMTRAK. Tell your healthcare provider if you get symptoms of liver problems such as right-sided abdominal pain or yellowing of the skin or eyes.

The most common side effects of KIMMTRAK include: • cytokine release • stomach pain syndrome (CRS) • swelling • rash • low blood pressure (symptoms may • fever include dizziness or light-headedness) • itching • dry skin • tiredness • headache • nausea • vomiting • chills • abnormal liver blood tests These are not all the side effects possible with KIMMTRAK. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 (1-800-332-1088).

Please read the Patient Information before you receive KIMMTRAK and discuss any questions you have with your healthcare provider.

Please see complete KIMMTRAK Patient Information on the following page.

HLA-A, human leukocyte antigen-A. † Other treatments studied: pembrolizumab, ipilimumab, or dacarbazine (chemotherapy).

Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive KIMMTRAK? This information does not take the place of talking to your healthcare provider about your condition or treatment.

To learn more about KIMMTRAK, you should talk to your healthcare provider or pharmacist. To obtain the FDA-approved patient labeling call 844-775-2273 or visit www.KIMMTRAK.com.

What is KIMMTRAK? KIMMTRAK is a prescription medicine used to treat HLA-A*02:01-positive adults with uveal melanoma that cannot be removed by surgery or has spread. Your healthcare provider will test you for the presence of the HLA-A*02:01 gene to make sure KIMMTRAK is right for you.

It is not known if KIMMTRAK is safe and effective in children.

KIMMTRAK will be given to you by intravenous (IV) infusion into your vein for 15 to 20 minutes.

• KIMMTRAK is usually given every week.

• Your healthcare provider will decide how many treatments you need.

• Your healthcare provider will keep you under observation for at least 16 hours following the first three KIMMTRAK treatments and for at least 30 minutes after future treatments.

• Your healthcare provider may delay your treatment of KIMMTRAK if you have certain side effects.

• Your healthcare provider may do blood tests regularly during treatment with KIMMTRAK. What are the possible side effects of KIMMTRAK?

What is the most Important Information I should know about KIMMTRAK?

KIMMTRAK can cause other serious side effects, including:

KIMMTRAK can cause serious side effects that can be severe or life threatening and usually happen within the first three infusions, including:

• See “What is the most important information I should know about KIMMTRAK?”

• Cytokine Release Syndrome (CRS). Symptoms of CRS may include: - fever - low blood pressure - tiredness or - dizziness and lightweakness headedness - vomiting - headache - chills - wheezing and trouble breathing - nausea - rash Tell your healthcare provider right away if you get any of these symptoms. Your healthcare provider will check for these problems during treatment with KIMMTRAK. Your healthcare provider may temporarily stop or completely stop your treatment with KIMMTRAK if you have severe side effects.

See “KIMMTRAK can cause other serious side effects” for more information.

What should I tell my healthcare provider before taking KIMMTRAK? Tell your healthcare provider about all of your medical conditions, including if you: are pregnant or plan to become pregnant. KIMMTRAK may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with KIMMTRAK.

• Skin reactions. KIMMTRAK may cause skin reactions that require treatment. Tell your healthcare provider if you get symptoms of skin reactions—such as rash, itching, or skin swelling—that are severe and do not go away.

• Abnormal liver blood tests. Your healthcare provider will do blood tests to check your liver before you start KIMMTRAK and during treatment with KIMMTRAK. Tell your healthcare provider if you get symptoms of liver problems such as right-sided abdominal pain or yellowing of the skin or eyes.

The most common side effects of KIMMTRAK include: • cytokine release • stomach pain syndrome (CRS) • swelling • rash • low blood pressure (symptoms • fever may include dizziness or • itching light-headedness) • tiredness • dry skin • nausea • headache • chills • vomiting • abnormal liver blood tests These are not all the side effects possible with KIMMTRAK. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA1088 (1-800-332-1088).

For females who are able to become pregnant: • Your healthcare provider should do a pregnancy test before you start treatment with KIMMTRAK. • Use an effective form of birth control during treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK. • are breastfeeding or plan to breastfeed. It is not known if KIMMTRAK passes into your breast milk. Do not breastfeed during the treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK.

General information about safe and effective use of KIMMTRAK. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information.

If you would like more information about KIMMTRAK, talk with your healthcare provider. You can ask your healthcare provider for more information about KIMMTRAK that is written for healthcare professionals.

Immunocore and KIMMTRAK are registered trademarks of Immunocore Ltd. ©2022 Immunocore Ltd. All rights reserved.

Accelerated Approval Delivers Hope for Rare Diseases The Accelerated Approval Pathway has delivered innovative therapies to rare disease patients for three decades.

H

owever, the recent and controversial approval by the Food and Drug Administration (FDA) of an Alzheimer’s therapy could lead Congress to reevaluate the program. Any reforms must preserve and strengthen this important tool for innovation, not just throw out the baby with the bathwater.

Background In 1992, the FDA, Congress, and the public joined forces to give the FDA flexibility in the drug approval process to expedite scientific discoveries into treatments.

This AAP is designed to carefully speed access to new drugs, while preserving the FDA’s gold standards for safety and efficacy — the same approval standard as all approvals. Accelerated approval simply permits the FDA

to accept a different type of data for approval. In exchange, the drug company must conduct post-approval studies to confirm the expected benefit.

In the United States, a rare disease is one that affects fewer than 200,000 people. According to the National Institutes of Health, there are thousands of rare diseases that together affect as many as 30 million Americans.

These are often serious or life-threatening diseases — 80 percent are genetic in origin, 50 percent impact children, and 30 percent of those children will not live to see their fifth birthday. Yet, there are only approximately 700 drugs currently approved for rare diseases.

Overcoming challenges Developing drugs for rare diseases can be challenging due to specific characteristics such as small heterogeneous patient populations, long

timeframes for disease progression, a poor understanding of disease natural history, and a lack of prior clinical studies. Therefore, the AAP pathway is an essential tool used to bring new treatments to patients living with a rare disease.

By relying on surrogate and intermediate clinical endpoints, sponsors can bring therapies to market under shorter timeframes, with less cost and smaller participant groups than traditional clinical trials, and patients can have earlier access to these medicines.

We at the Rare Access Action Project (RAAP), agree with Dr. Richard Pazdur of FDA’s Oncology Center of Excellence when he says that instead of attacking the program, we need to address “what’s going right” with it. There have been 165 accelerated approvals over the past 10 years, with only about 10 therapies removed from the market.

As Congress considers FDA’s user fee programs, which are up for reauthorization this year, it is likely the AAP will also be a key topic of debate.

Let’s not allow the recent controversies obscure the overall dramatic successes of the program.

Without accelerated approval, many with rare diseases would be left with few, if any, treatments because traditional clinical trials would be nearly impossible to conduct.

As the 30-year anniversary of AAP approaches, RAAP urges that any potential changes be designed to strengthen the areas of success and reinforce tools that offer patients access to medicines that can treat serious and life-threatening rare diseases and conditions. n Michael Eging, Executive Director, Rare Access Action Project

MEDIAPLANET 15

convenient because it’s administered once or twice a month.

Most people receiving these treatments have a bleeding incident one to two times a year.

Challenges The biggest challenges for people with hemophilia are access to care and cost.

Many patients struggle to afford premiums for comprehensive insurance coverage and out-of-pocket expenses for medication.

“They’re a disproportionate share, high-cost claimant, meaning we have 30,000 hemophilia patients in the country, and yet they sit on the top 10 to 15 of the high-cost claims list,” said Kollet Koulianos, M.B.A., the VP of payer relations at NHF. “It’s very expensive.”

How New Research and Treatments Can Help People with Hemophilia Hemophilia — an inherited bleeding disorder in which blood doesn’t clot normally — is treatable, and even more treatments may be on the horizon.

The chronic condition is marked by bleeding longer than other people, spontaneous bleeding, and bleeding into a joint after surgery or injuries. An untreated bleed can cause permanent debilitating pain, or death if it’s in a major organ.

There are two types of hemophilia: hemophilia A and hemophilia B. Proteins in the blood called clotting

factors help stop bleeding, but people with hemophilia A have low levels of clotting protein factor VIII, while those with hemophilia B have a deficiency of clotting factor IX (FIX).

“It was once considered to be a disease that resulted in death usually in the second decade of life,” said Dr. Len Valentino, a hematologist and CEO of National Hemophilia Foundation (NHF), one of the nation’s leading patient advocacy organizations for the inheritable blood and bleeding disorders community. “But people with hemophilia now can live a full, enriched life.”

16 READ MORE AT FUTUREOFPERSONALHEALTH.COM

Current treatments Hemophilia A is treated by replacing the missing protein, which allows the person with the condition to form clots, helping to reduce or eliminate the bleeds associated with hemophilia. Hemophilia B is typically treated with a concentrated FIX product, known as “clotting factor” or simply “factor.”

The therapies are infused intravenously through a port in the chest or a vein in the arm every few days. A subcutaneous monoclonal antibody, which has been in use for the past four years, makes the treatment far more

Gene therapy Gene therapy — modifying a person’s genes to treat a condition — may be the future of treating hemophilia.

Gene therapy clinical trials are underway, and Dr. Valentino says, so far, there are no significant safety or efficacy concerns.

“Patients don’t need to inject additional factor after the gene therapy begins to work, which is usually somewhere between two and four weeks after it’s administered,” he said, noting 40 to 50 percent of patients require steroids to control any immune response after they receive gene therapy, and they’ll need a lot of clinical follow up.

While gene therapy will likely be expensive, patients may choose this new treatment option.

“People may be likely to say, ‘I’m willing to do this because I want to have the opportunity to be living this normal life without hemophilia, and I also want to help advance treatments for future generations,’” Koulianos said.

NHF encourages patients to talk with their providers about potential therapies or treatments for their hemophilia. n Kristen Castillo

MEDIAPLANET

The Barriers Black Families Face When Confronting Rare Disease

C

aring for a child with a rare disease is difficult for any family. It can be nearly impossible to find a physician who is able to correctly diagnose and offer treatment for the child’s condition, and a cure may not exist at all.

People of color face even more barriers to finding proper care. A history of abuse and racism still permeates our healthcare system today.

Deavin Arnold-Hadley and her family experienced the gravity of this crisis when they were seeking diagnosis, treatment, and support for their son who had a rare form of epilepsy.

“When we began our journey, we had no idea how to advocate for our son,” she says.

Searching for answers Arnold-Hadley and her husband Chad had Mason, their second child, in 2010. Mason was hitting developmental milestones early on, but he began showing symptoms of epilepsy around age two.

“It was excruciating to watch Mason endure hundreds of seizures a day,” Arnold-Hadley says. “We felt helpless watching his cognition and personality deteriorate.”

It took consultations with multiple doctors to properly diagnose Mason with Doose syndrome, a rare, catastrophic

form of epilepsy that accounts for less than 2 percent of all childhood-onset epilepsy cases.

However, just because they knew what was going on with their son didn’t mean treatment would be easy to find.

Doose syndrome has no known cause or cure, and Arnold-Hadley reports her son wasn’t being invited to participate in the clinical trials that other patients with similar conditions were benefiting from.

“That created unnecessary burdens that compound the fact that Mason struggles with a rare disease,” she says.

Many of the treatments Mason were offered came with devastating side effects and unknown long-term complications. The family eventually decided the best course of action was to try putting Mason on a medical ketogenic diet, which is designed to mimic the effects of fasting and get the body to use fat stores as its main source of fuel. Research has shown the diet to be effective in mitigating epileptic symptoms, especially for Doose patients.

“Our family made the decision to turn away from traditional forms of medicine and start focusing on new therapeutic methods,” Arnold-Hadley says.

Fortunately, the diet was a smashing success. Now 10, Mason is still using a keto diet

18 READ MORE AT FUTUREOFPERSONALHEALTH.COM

PHOTO: COURTESY OF THE HADLEY FAMILY

A mother recounts her journey of finding proper care for her son when he was diagnosed with a rare form of epilepsy.

to manage his symptoms while he engages in homeschooling.

Lending a hand The Hadley family’s tale underscores a health crisis at the intersection of rare disease, race, and culture.

“Diversity, inclusion, and cultural concerns for the African American population have been highlighted in a multitude of settings recently,” says Lorraine Newborn-Palmer, DNP, RN, ACNS-BC, CNRN, CBIS, a member of the Epilepsy Foun-

dation’s Professional Advisory Board. “As an ethnic group, conditions such as epilepsy are being discussed more often in the context of historical backgrounds and now in the face of an ongoing pandemic.”

Arnold-Hadley has used this experience to empower and advocate for others. She’s spoken to medical professionals on behalf of The Black Women’s Health Imperative, shedding light on the damage a delayed diagnosis and treatment plan can cause. She’s also been a key-

note speaker at epilepsy-related conferences and retreats.

“It’s so important to find the right medical provider for your family,” Arnold-Hadley advises other parents facing similar situations. “Some physicians were not a good fit for our family. We were able to find one that worked together with us and didn’t just tell us what to do. We made medical decisions together.” n

Dustin Brennan

How This Fitness Coach and Influencer Took on Cystic Fibrosis and Won Cystic fibrosis is a hereditary disease commonly associated with low life expectancy, but fitness coach Sophie Grace Holmes wasn’t about to let that be her story.

A tough road ahead Cystic fibrosis (CF) is a hereditary disease in which the body produces thick and sticky mucus that can clog the lungs and pancreas. It is usually diagnosed in infants and young children, and it can be life threatening.

“When I was born, it was predicted I wouldn’t make it to 16 years old.

When I was 19, I was told I wouldn’t make it to 21,” Holmes says. She explains that the diagnosis can be daunting for parents, especially considering the poor life expectancy associated with the disease.

“Thankfully, my parents were determined to do all they could to stay positive and do everything they could to ensure my health was the best,” says Holmes. “They also remained hopeful and positive, and they encouraged me to live a big life no matter what.”

Wanting more CF can make athletics difficult, but

PHOTO: COURTESY OF DAVID CARTER (@DAVIDCARTER_98 ON INSTAGRAM)

“Fitness has saved my life,” says fitness and nutrition coach Sophie Grace Holmes. “It’s taught me who I am and what I am capable of by pushing boundaries over and over again.”

The athlete and influencer was diagnosed with cystic fibrosis at four months old. Despite dire life expectancy predictions, Holmes has never let the condition get in the way of who she is and the life she wants to live.

Holmes says this only encouraged her to achieve bigger and better things than doctors predicted she could.

“I have always naturally been positive, striving to become the person I am meant to be,” she says. She explains she always wanted not to “survive but thrive” and calls CF her “driving force” not her “definition.”

“Big goals push me,” Holmes says.

“Having stories to tell and adventure

— especially physical adventures — that’s where my passion lies. I am truly grateful for my CF, and for the big unique life it has given me. Without it, I would not have experienced so much at such a young age, from climbing some of the highest mountains in the world to crossing oceans.”

Holmes also welcomed the challenge the pandemic presented to her business and used it as an opportunity

to grow and become more creative. “By being vulnerable — I had to stay in my house for 14 weeks — this allowed me to reinvent and recreate my business, my life, and a way of living I had been working for basically overnight.”

She found a way to take her business online, create her fitness app, leverage the power of social media, and find brands that complemented her training and her health. And the results were worth it.

“I am the strongest and healthiest I’ve ever been,” she says. “It’s allowed tremendous growth in my mindset, the willingness to take a risk, but also really shown me my passion for what I want to do for work — transform as many lives as possible through fitness and mindset.”

There is no cure for CF, but the condition can be managed through specialized treatments including antibiotics, and through nutrition, which is also a part of Holmes’ fitness regimen and coaching.

But whatever anyone else’s personal journey or path might be, Holmes’ central message stays the same: everyone is able to achieve something extraordinary.

“I am a seeker of opportunity no matter what life is throwing at us,” Holmes explains. “Life is about your perspective and being creative to continually take steps forwards no matter what. I believe what’s meant for you won’t pass you by and usually these obstacles can lead to things better than you could ever imagine.” n

Lynne Daggett

MEDIAPLANET 19