How drugs for rare diseases make it to the people who need them
Fact checked by Shannon Sparks
Known as “butterfly children,” their skin is so delicate it tears at the slightest friction. Everyday tasks — dressing, walking, even eating — can cause blisters and cuts.
These children have a rare disorder called epidermolysis bullosa, or EB. This life-threatening genetic skin disorder affects an estimated 500,000 people worldwide, including nearly 50,000 in the United States.
For decades, patients had no approved treatment options. In the past two years, however, three therapies have gained Food and Drug Administration (FDA) approval — a dramatic shift in a field where most rare diseases lack a single approved drug.
“More important today than ever is good data. Data drives decisions and creates incentives in the rare disease ecosystem,” says Michael Hund, CEO of EB Research Partnership, the largest global nonprofit dedicated to funding research to treat and cure EB.
Rare disease drug development follows the same regulatory framework as other medicines — but with higher hurdles. Here’s how it happens.
Building the knowledge base
Researchers often begin with natural history studies and biobanks — repositories of genetic and clinical information that track disease progression. For EB, clinicians at Stanford University and Cincinnati Children’s Hospital Medical Center launched a 22-hospital EB Clinical Research Consortium. The group shares information through a centralized database, expanded with philanthropic funding.
“Simply put, when PhD researchers are working on solutions, the ultimate goal is what we call ‘from bench to bedside,’” Hund says.
That translation requires clearing what researchers refer to as “the valley of death” — the gap between promising laboratory findings and first human trials. Sponsors — organizations leading the study — must submit an Investigational New Drug application to the FDA, which includes preclinical safety data, manufacturing plans, and proposed study protocols to demonstrate that the treatment is reasonably safe and capable of measuring a defined outcome.
The hurdle of limited literature
Many academic discoveries stall before human testing because of cost and regulatory complexity. Melissa Byrn, assistant dean for clinical research at the University of Chicago, says rare diseases face additional hurdles.
“Historically, there has been less research on those diseases or pathways that lead to them,” Byrn says. “So we have limited literature.”
A thinner scientific foundation makes it harder to identify drug targets, design trials, and attract investors. “The process and the requirements are the same,” she says. “You still have to prove that something’s safe and effective. But finding funding to support the expense of bringing a drug or device to market is more challenging.”
David Gortler, PharmD, former senior advisor to the FDA commissioner on science policy, says the process moves from preclinical testing in cells and animals to first-in-human studies, followed by multiple clinical phases.
“There are legal steps, preclinical steps, and then four clinical phases,” Gortler says. “The reports I used to write at the FDA for these [human study reviews] were routinely hundreds of pages long.”
Challenges in clinical trials
Early-stage trials may enroll as few as five patients to assess safety. Later phases expand enrollment to evaluate effectiveness, dosing, and manufacturing at scale.
Recruitment is especially difficult for rare diseases. EB’s four major subtypes, for example, each correspond with specific genetic mutations. Most trials focus on a single subtype, shrinking the pool of eligible participants. And potential participants may live far from medical centers, forcing families to navigate long trips, missed work, and time away from school.
“The biggest barrier for EB, and largely across rare diseases, is clinical trial recruitment — really finding the patients,” Hund says.
Smaller clinical trials can complicate the interpretation of safety data. “When you’re only testing in a few dozen or a few hundred people, you don’t have the same depth of data,” Gortler says.
Incentivizing innovation
Federal policy heavily influences participation. The Orphan Drug Act of 1983 created incentives for developing treatments for conditions affecting fewer than 200,000 Americans. Drugs developed for rare diseases are known as orphan drugs because the pharmaceutical industry historically neglected such therapies due to limited financial returns in small populations. Benefits include seven years of market exclusivity, tax credits for clinical testing, and eligibility for expedited FDA programs such as Fast Track and Breakthrough Therapy designations.
Fast Track designation speeds development and review for drugs that treat serious conditions and address unmet needs. It allows frequent FDA communication and rolling review of application materials as they’re submitted.
Breakthrough Therapy designation applies to drugs that show substantial improvement over existing treatments based on early clinical evidence. It provides intensive FDA guidance and is eligible for all Fast Track designation features.
The Orphan Drug Act also created priority review vouchers. When a company wins approval for a qualifying rare disease drug, it receives a voucher that speeds FDA review of another product. Companies can use or sell the voucher.
In 2025, Abeona Therapeutics, which developed an FDA-approved gene therapy for EB, sold its voucher for $155 million.
Hund calls the framework innovative. “If that provides an incentive for companies to develop therapeutics for rare diseases, then ultimately rare disease patients benefit,” he says.
Gortler says expedited programs still require rigorous evidence. “Not all drugs are approved automatically,” he says. “It requires the work of pharmacists, pharmacologists, toxicologists, chemists, physicians — hundreds of people.”
“Special approval pathways introduced by the FDA, like the Fast Track designation, can speed up the development and review process for drugs that treat serious conditions and fulfill an unmet medical need,” Byrn says. “But it does not eliminate scientific standards.”
For families living with EB, the journey doesn’t end with FDA approval. Access, insurance coverage, and the logistics of ongoing treatment remain daily challenges.
Hund says patient registries and advocacy networks are crucial to advancing research. “Families and patient groups aren’t just participants; they’re partners,” he says. “Their insights help shape which endpoints matter most and ensure therapies truly address patient needs.”
For butterfly children, each step forward in research and drug development represents more than a regulatory milestone — it means stronger skin, fewer hospitalizations, and the possibility of living a longer, fuller life.
