February 28, 2019

Rare Disease Day Symposium Meeting Highlights:

Today’s Rare Disease Landscape

In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people, so it may be counterintuitive to realize that rare diseases cumulatively are not in fact rare. An astounding 7,000 rare diseases are known, and 30 more are being described each year. Eighty percent of these are genetic disorders, affecting 3 to 4 percent of all births. Although the number of individuals suffering from a single rare disease is small, the total number of individuals suffering from a rare disease is significant.

Prior to 1983, only a small number of rare diseases had approved therapies. Today, 302 rare diseases have approved therapies. In the last five years alone, 21 novel first-in-class treatments were approved for treating rare diseases. At present almost 600 companies are developing novel rare disease therapies, and there are now 729 gene therapies being studied in 1,855 clinical trials.

There are still significant challenges. In the diagnostic realm, the journey to diagnosis remains lengthy, complex and often ineffective, compounded by a lack of rare disease experts in any given geographic area. In the research arena, investigators confront many unknowns regarding a disease’s natural history or what endpoints and benefits should be considered meaningful to patients—and payers. There are a limited number of patients available to participate in often-competing clinical trials. Complicating all of this is that return on investment for companies sponsoring these trials is often uncertain and the reimbursement landscape for rare disease therapies remains volatile: both have important implications for patient access to effective treatments.

Nevertheless, numerous areas of progress and opportunity can be seen in the following examples: curative potential of gene therapies, growing networks of providers sharing information and referrals, increased data generation and sharing, and continued regulatory support and innovation with positive approval trends. Importantly, patients, their families and advocates have been driving forces at the center of many of these innovations, and their voices are being heard and growing stronger.

Pioneering Progress: The North Carolina Example


Many of these positive trends have converged in North Carolina, where bipartisan legislation was passed overwhelmingly in 2015 to establish the North Carolina Advisory Council on Rare Diseases. The legislation was called “Taylor’s Law,” after Taylor King, a young girl who had been diagnosed with infantile Batten disease in 2006. Her mother, Sharon King, leads the Charlotte, N.C.-based rare disease advocacy group Taylor’s Tale, which raises funds for research and promotes public awareness.

Based at the University of North Carolina at Chapel Hill, the Advisory Council advises state government on rare disease research, diagnosis, treatment and education. The group consists of rare disease clinicians, nurses and researchers; patient advocates and survivors; and the Secretary of the N.C. Department of Health and Human Services, as well as includes representation from UNC-Chapel Hill and Duke University.

“The goal was always to be a statewide initiative,” said Tara Britt, associate chair of the Advisory Council and development officer for the UNC School of Medicine. “It took the collaboration of many people, making a clear case it would benefit both the rare disease community and the state, to move this forward.”

Creation of the N.C. Advisory Council on Rare Diseases has been a powerful catalyst for collaboration, including:

  • A task force led by patient advocates that has recommended focused efforts to address newborn screening for rare diseases and genetic testing.
  • A Rare Disease Network designed to solicit feedback and foster collaboration statewide among patients, advocates, academics, healthcare systems, industry, state/federal agencies and foundations.
  • Work statewide, led by the North Carolina Patient Coalition, to build a patient resource portal as a central resource for information and data on rare diseases in the state.


In addition, UNC Medicine has established the Rare Disease Partners Program, a philanthropic engagement to foster innovative academic/ industry collaborations.

"We all have so many strengths. It’s been an amazing journey seeing us all collaborate, accomplish great things with more on the way, and set an example for other states."

The Patient Advocacy Experience:

The Power of One

In 1987, a 39-year-old man named George McCoy with severe hemophilia volunteered to be the first human infused with a genetically engineered medicine—a recombinant DNA clotting factor. There was an urgent need for this new therapy. At the time, many in the hemophilia community—young children and adults—were dying of AIDS after receiving HIV-contaminated clotting factors derived from human plasma. The first recombinant therapy for hemophilia was approved by the FDA in 1992, and George went on to become a passionate advocate for the bleeding disorders community and founding father of the patient advocacy organization Hemophilia of North Carolina.

“George McCoy was one of my biggest mentors,” said Charlene Cowell, executive director of Hemophilia of North Carolina. “He experienced years of pain and lack of mobility, and he was determined to change that for others. He participated in many clinical trials, and we all need to do what George was willing to do and drive research forward.”

Charlene emphasized the “indescribable impact” that one person can have, as well as the need to work together for change. She encouraged individuals interested in advocacy to take concrete steps: If an organization has a mailing list, get on it. Attend events to hear from patients and those who represent them. Participate in consumer advisory boards.

“If you are feeling alone, reach out to patient organizations and ask for support. You may not realize how many people are there for you,” Charlene said. “Think of George or find your own inspiration. Imagine what kind of a future is possible if we all play a part.”

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“My Reasons Why”: One Mother’s Advocacy Journey


The inspiration for Kathleen Henry becoming a rare disease advocate and North Carolina Ambassador for NORD was just within a hug’s reach. She’s a mother of three with two children who were diagnosed with rare forms of cancer. She spoke powerfully about her children’s challenges and her own. “One of the hardest things was the lack of diagnosis for so long, and by then my son’s condition had become severe,” she said, speaking of her son Collin’s diagnosis at age 2 with acute lymphoblastic leukemia. Her son Patrick was diagnosed at age 6 with hepatoblastoma, a very rare form of liver cancer.

“What motivates me to be an advocate is that my whole job as a parent is to take care of my kids and to make sure they are safe and protected, that they can grow up and have a future,” Kathleen said. “Childhood cancer stole a lot of power from me as a parent, and I don’t like feeling helpless. Advocacy was a way for me to take some of that power back.”

The same goes for children. Her sons have visited with state and federal lawmakers. Students at her son Patrick’s middle school have embraced advocacy, learning about rare diseases and holding public events to share what they know (and often their own experiences) with others. “Kids in politics might seem strange,” Kathleen said, “but kids are incredible if we teach them to use their voices.”

“Living with rare disease, especially in this age of social media, we tend to put ourselves in fishbowls—everything that has happened to us has been documented,” she continued. “So use that data to advance understanding. Ask us difficult questions. Even if we start crying, it’s okay—it’s just an emotion. Ask the kids questions—they have so much to say.”

Kathleen’s very personal, and often difficult, story reminds us that the impact of rare disease, while being often debilitating, overwhelming and negatively life changing for the patient, is felt intensely by those around the patient as well. The collateral damage to family and caregivers should not be underestimated—or ignored for lack of support—in our efforts at progress.

The FDA and Rare Disease Policy:

Making Progress

When it comes to orphan drugs for rare diseases, the FDA faces a classic quandary: Some will criticize it for moving too slowly to approve new therapies for patients who desperately need them; others will criticize it for being too quick to approve too many new, unsafe drugs. As Peter Pitts, president of the Center for Medicine in the Public Interest and former FDA associate commissioner, pointed out, one’s view largely “depends on where you sit.” He made the case, however, that the FDA has been appropriately cautious while facilitating regulatory pathways to expedite medicines to patients suffering from serious and life-threatening conditions.

Several recent FDA initiatives hold promise for further supporting and accelerating rare disease research and development:

  • In January 2019 the agency announced the formation of an Office of Drug Evaluation Science (ODES) with three divisions focused on clinical outcome assessments, biomedical informatics, safety analytics and biomarker development.
  • In December 2018 the agency released its Framework for FDA’s Real- World Evidence Program. Real world evidence (RWE) is about the usage, safety or efficacy data of a drug from sources other than traditional clinical trials. Using it to improve regulatory decisions has become a top strategic priority at the FDA and advocates have generally applauded this to as a way to make clinical trials for new therapies more flexible and responsive to the needs of rare disease patients.
  • The FDA’s Patient-Focused Drug Development initiative seeks to engage patients and reflect their perspectives and needs more directly in regulatory decision making.


“The move toward patient-focused drug development is an important opportunity for patients and advocates to translate their experience and passion into usable information for regulators,” said Peter. “To be true partners, though, patient input will need to be more data-driven and outcomes focused. Nowhere is that more urgently needed than in discussions about the benefits and risks of new therapies.”

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Access and Coverage: The Payer Perspective


New therapies can’t make a difference in people’s lives if patients and their families can’t afford them. Research and development in rare disease is inherently expensive; however, making access to therapy— and the payer role in enabling that access—a critical issue for the rare disease community.

“Currently, payers focus most on the clinical benefits and outcomes of a therapy, and the direct medical costs associated with it,” said Ed Pezalla, MD, MPH, founder and CEO of Enlightenment Bioconsult and former vice president of pharmaceutical policy and strategy for Aetna. “They currently pay less attention to other things of importance to patients, such as quality of life, function and disability. They probably pay even less attention to things that are relevant to society, such as the toll of caregiving and impacts on productivity.”

Ed cautioned that simply talking about the unmet needs before us won’t be enough to bridge that gap. When patients, providers and industry say, “this is a rare disorder with few or no viable treatment options,” payers hear “this will be a high cost per patient, for a difficult-to-identify patient population, and outcomes will be uncertain because of limited clinical trials.”

To solve for this disconnect, Ed sees opportunities for companies to focus on helping reduce payer uncertainty and risk. Reducing uncertainty can involve studying the natural history of the condition and its costs, developing diagnostic algorithms, and working with professional societies and others to define diagnostic protocols. Reducing risk can involve developing frameworks for outcomes-based pricing, conducting follow-on studies and providing tools for determining response to therapy.

“Exploring innovative contracts and financing is another way to reduce uncertainty, shift risk, and align payment with value received,” said Ed. “There are multiple options, but their common basis is the availability of clinical outcome measures to assess benefit.”

"Currently, payers focus most on the clinical benefits and outcomes of a therapy, and the direct medical costs associated with it."

A Legislator’s View

“I think it’s safe to say that legislators don’t always listen to their constituents, which is a shame,” began Representative Becky Carney, a member of the North Carolina General Assembly’s House of Representatives District 102. “One day one of my constituents reached out to me to talk about establishing a rare disease network in the state. Her name was Sharon King, and her daughter Taylor had a rare disease. I’m very glad I listened.”

Becky became a lead sponsor of Taylor’s Law, the bipartisan legislation that established the North Carolina Advisory Council on Rare Diseases in 2015. She described the process leading to the bill’s passage, including the first necessary step: educating legislators about rare diseases and how they affect many more people in their districts than they might realize. Buoyed by the wellspring of support the bill received from patients, advocates, government officials, industry and others, it took just three months for Taylor’s Law to pass—which it did just six hours before Becky, confronting her own health crisis, was scheduled for open heart surgery. She listened in from her hospital room.

“I learned from my own experience just how great the needs are in our state for medical research, the tremendous healthcare resources we have here and the importance of continuing to invest in those resources,” reflected Becky. “So as a legislator but also as a patient, parent and advocate, it was like reaching the summit when Taylor’s Law passed that day.”

Industry Perspective: “Everything is Today”

Moke Sharma, head of development operations and quantitative sciences at Alexion Pharmaceuticals, began his remarks by observing, “One distinguishing feature of working for a company conducting research in rare diseases is that you are much closer to the patient community than in just about any other therapeutic area. From that you get absolute clarity on why you have to work so hard to research and develop new treatments—because if you don’t, there’s nothing else to help these patients. Everything is today.”

Moke sees the long route to diagnosis and the problem of access, even with good insurance, as two of the defining challenges facing the rare disease community. “A large portion of our work focuses on awareness and education, so when a provider sees a patient with certain symptoms, they will more readily suspect a rare disease and consider diagnostic testing or referral.” Regarding access, he said, “The drugs we develop for rare diseases do one thing only and for a very small group of patients. To recoup our investment, gain reimbursement and ensure patient access, we need to deliver value, a meaningful benefit. We need to transform.”

The FDA has been supportive—accepting new endpoints, working with sponsors when a trial “fails,” evaluating the totality of the data and being willing to discuss challenges. “We don’t have everything we’d like from the FDA, but it really is up to us to fully engage with them so that their challenges become ours as well, so that we can deliver what they need to get new therapies to patients more efficiently.”

Clinical Challenges:

Screening, Early Identification and Treatment

All too often, this happens: A young child presents with developmental delays or other easy-to-dismiss signs and symptoms. Over time the parents can see something still isn’t right. Further testing proves inconclusive until symptoms become pronounced and finally—often months or years later—their child receives a rare disease diagnosis.

“We often see patients with this long history of diagnosis,” said Cynthia Powell, MD, professor of pediatrics and genetics at the UNC School of Medicine. “It would be much better to catch these much earlier through newborn screening, which we can only do now for just a few rare diseases with a genetic component.”

One problem is that the evidence base for many conditions nominated to be included in standard newborn screening programs is weak. “Rare diseases are caught in a classic ‘catch-22’ situation,” Cynthia explained. “Screening cannot be mandated without evidence of benefit, but screening is needed in order to gather that evidence.”

The proposed solution: a collaborative initiative called Early Check—a voluntary newborn screening program being offered for each of the approximately 120,000 babies born each year in the state, designed to advance research to better inform newborn screening policy for rare conditions. “The goals of Early Check include helping us understand the early natural history of ‘screen positive’ infants, and enabling research on the benefits of early detection and treatment.”

The next challenge? Addressing the acute shortage of experts (geneticists, neurologists, pediatric subspecialists) trained to diagnose and treat people with rare diseases. The sobering fact is that approximately 50 percent of positions in medical genetics/genomics go unfilled annually in the U.S. “In North Carolina we have a shortage of pediatric subspecialists and child neurologists, and only two training programs with many unfilled faculty positions,” said Cynthia. “This shortage is one of the main reasons the diagnostic and treatment journey is so difficult for so many, and dealing with it needs to be high on our priority list.”

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Discussion: What Comes Next?

From one person’s inspirational advocacy to another’s ambitious collaborative research effort, Symposium presenters and participants shared compelling stories of meaningful progress, personal pain and growth, and deep commitment to the cause of advancing research and care for people living with rare disorders. For many the event was inspiring and energizing—a good thing, because also clear was that many challenges for concerted action remain. Actionable insights arising from the discussion included opportunities to:

  • Further empower patients and families. This includes making sure that information and resources, including training in advocacy skills and coalition building, are widely available to enable people to be effective advocates—both for others and for themselves. Coping with a rare disease can be very isolating; expanding sources of support and connecting people in the community to each other is an ever-present need.
  • Amplify the patient voice in rare disease R&D. Trends toward patient-focused drug development mean more opportunity for patient participation, particularly with regard to research study design, outcomes assessment and benefit/risk analysis. More can be done to seek out the patient voice in the process. At the same time, providing patients with skills for “speaking the same language” as researchers and regulators—being more data-driven and outcomes focused—will help strengthen their voice at the table.
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  • Evolve clinical trial design and endpoints. Make these more patient-centered to facilitate clinical trial participation, and ensure assessment of outcomes that are most meaningful to patients.
  • Expand access to rare disease therapies. Drug developers can sharpen focus on ensuring their evidence generation strategy (including outcomes data and real world evidence) is conceived from the beginning to support reimbursement by demonstrating tangible value to payers. They are also in a unique position to reduce payer uncertainty and sense of risk by providing more data on the natural history of the disease, current treatments, cost implications and outcomes. Innovative trial designs such as platform trials can target a variety of subtypes of a disease, thereby expanding access to experimental therapies.
  • Accelerate diagnosis. To help promote earlier identification and/or referral, more education directed to providers is needed. Because so many rare diseases are genetic in origin, continuing to build the evidence base for conditions to be included in standard newborn screening programs is imperative, following the lead of initiatives like North Carolina’s Early Check program
  • Build clinical expertise and manpower. Even when therapy for a rare disease is available, care for patients is hampered by a lack of experts (geneticists, neurologists, pediatric subspecialists) to diagnose and treat them. Greater effort is needed to attract and retain expertise, fund training programs and boost the number of qualified applicants.
  • Lead the way, by example. The efforts and successes to date of the rare disease community in North Carolina have given all involved a unique, 360-degree perspective on what it takes to advance diagnosis, research and care for patients and families. “Our job has been to pioneer,” said Tara Britt toward the end of the symposium, “and now it’s time to bring others along.”


In that spirit, the symposium brought together a wide array of perspectives and people dedicated to moving forward on these and other priorities. This report of the discussion that ensued offers a road map to some of the immediate opportunities available to us for deepening our connections and engagement with each other in support of the rare disease community.