Inside the Orphan Drug Revolution

Damian Doherty talks to James Geraghty about his new book

Jim Geraghty
Jim Geraghty

Jim Geraghty, a seasoned biotech executive and a veteran of the orphan drug movement since its inception, took some time to talk to Damian Doherty about his new book, Inside the Orphan Drug Revolution. Jim gives an historical perspective of the leading protagonists who drove this revolution forward and gives often deeply personal accounts of the patients and parents who had to navigate a trepidatious path, risking new and unproven therapies. He deftly balances issues such as pricing, politics, misaligned incentives, and ubiquitous access and gives the reader a peek into the future with the promise of next generation gene therapies and editing techniques and how these could impact the rare disease community. He cautions that, as we’ve witnessed recently, things can easily unravel and continued progress ultimately depends on constant vigilance.

Q:  First of all congratulations on a wonderful book, how long had this project been incubating?

Inside the Orphan Drug Revolution book cover A: The idea for this book grew out of my helping with the book Conscience and Courage, a biography of orphan drug pioneer Henri Termeer, in 2019. I thought there was a broader story still to be told, and started in on it with the start of Covid quarantine in March 2020.

Q: For those of us who are uninitiated, what’s an orphan drug?

A: Orphan drugs are treatments for orphan diseases—the thousands of rare genetic diseases long “orphaned,” or ignored, by big pharma companies because they were too small to make money. In the U.S. they’re defined by the Orphan Drug Act as diseases affecting fewer than 200,000 people.

Q: What are some of the better-known rare diseases for which these drugs are needed?

A: Most people have heard of hemophilia, cystic fibrosis, or muscular dystrophy, all orphans. And almost everyone in the Black community knows the scourge of sickle cell disease among people of African descent. Few know the thousands of others unless they strike in their own families.

Q: Individually, each of these diseases is rare. But collectively what numbers are we looking at?

A: There are an estimated 7000 rare genetic diseases in total. These diseases afflict an estimated 25-30 million Americans, almost 1 in 10. And an estimated 95% of them still lack a therapy.

Q: In 1983, the Orphan Drug Act was passed. Did it do the trick, or is more legislation needed?

A: The Orphan Drug Act was critical to launching the orphan drug revolution. But we need stronger incentives to support investment for “ultra-rare” diseases—afflicting only tens or hundreds of people each—as most of that 95% are. We also need to find new ways to pay for a growing wave of one-time gene therapies that can save a lifetime of burden and cost but are expensive upfront.

Q:  You reference Harry Meade in chapter 6 and his statement on how ‘the suits manage to screw things up’- how critical is it that senior management in our Industry understand the importance of taking, at times, the unconventional route particularly when it comes to rare diseases?

A: Accepting and indeed embracing unconventional approaches is absolutely critical to success in the orphan drug world. Many if not most successful approaches grew out of ideas initially deemed impossible by the conventional wisdom.

Q: What is the revolution of which you’re speaking?

A: In the whole decade before the Orphan Drug Act fewer than 10 orphan drugs were approved; over 30 were approved just last year, and hundreds more are in development. And while Pharma long ignored the pleas of patients and families, biotech companies now actively court them.

Q:  For those of us who don’t have one of these diseases, and don’t have anyone in our family with these diseases, why should we care about orphan drugs?

A: Orphan drugs make a huge economic and social contribution by helping people live healthier lives, sparing their families fulltime caregiving, and avoiding millions of dollars in other costs. People should also care because genetic diseases don’t just “run in families,” as some assume, but in fact can strike any family at a birth of a child or grandchild, niece or nephew, without warning.

Q:  Do you think Pharma is doing enough to open up their vaults and let the rare disease community have access to some of their abandoned drugs?

A: Big Pharma companies are inherently bureaucratic and risk-averse,  but most want to see value realized by abandoned drugs and are open to trying, if cautiously,  to work with others who want to develop them.

Q: What has the orphan drug revolution taught us about ways to treat other, more prevalent diseases—like Parkinson’s, Alzheimer’s, and even high cholesterol?

A: Lessons from rare “monogenic,” aka single gene, forms of common diseases—Parkinson’s, Alzheimer’s, and others from high cholesterol to obesity—often show the way to new therapies for more common forms. Studying genetics has also helped us tailor common drugs to patients who will actually benefit, as many drugs work for only a subset of patients with common diseases, from melanoma to breast cancer to HIV/AIDS.

Q:  What will it take to sustain this revolution? 

A: Every year politicians hold hearings to reduce drug prices, which can sharply reduce the number of new drugs and how many people can get them. Only if people speak up will policymakers focus instead on reducing co-pays, which are what really limit access to critical orphan drugs.

Jim Geraghty
Jim Geraghty speaking at the opening of the Boston-area labs of
Canbridge Pharmaceuticals (a biotech company working to develop
orphan drugs for and in China)

Q:  In a post-Roe America and with implications around Mifepristone and Cushings Disease for example, do you genuinely worry things could reverse for the rare disease movement?

A: As I say in the book, the greatest risk to continued orphan drug innovation is complacency. If we take it for granted, drug price controls and other misguided policies can cripple it.

Q:  Peppered throughout your book are the stories of individuals who have personally benefited from these medications. Can you tell us about some of them?

A: The book opens with the stories of Abbey Meyers, who became the “mother” of the orphan drug revolution when a drug company stopped supplying a drug that worked for her son’s disease, and Brian Berman, whose treatment at age 3 allowed the first real biotech orphan drug to go forward. More recent examples are Pete Frates, who inspired the Ice Bucket Challenge that brought such attention to ALS (Lou Gehrig’s disease), and mothers who are leading efforts to fund R&D and get drugs approved for diseases from Duchenne’s (Pat Furlong) to Retts (Monica Coenraads).

Q:  What’s at stake for some of these people and their families?

A: Having a child with a serious genetic disease turns a family’s life upside down. Constant care, desperate efforts to find a treatment, and knowing your child may die before the age of 5, as 1 in 3 do, becomes all-consuming. Much of the work of the orphan drug revolution has been inspired by families who took on the mission of helping find a cure for children who come after theirs.

Q:  If you could change one thing today amongst all the
issues surrounding skewed incentives, industry greed, outdated payment models, rigid regulatory policies—what would it be?

A: One urgent need for many rare disease communities today is for regulatory and reimbursement policies that favor one-time genetic therapies over chronic lifetime therapies.

Q:  You’re not an MD. You come to all of this as a board member of five biotech companies. Is there a role for Big Pharma in all of this, or is it destined to be left to smaller biotech firms?

A: The orphan drug revolution was driven by the passion and risk-taking of physician-scientists and biotech entrepreneurs. Big Pharma can help in the marketing of approved drugs worldwide, but breakthrough innovation for new treatments will continue to come from smaller companies.

Q:  What big breakthroughs and developments are on the immediate horizon?

A: The orphan drug environment is active on many fronts. A gene therapy for hemophilia will come up for approval and reimbursement this year, decisions critical to the future of one-time therapy. Clinical trials will expand controversial “gene editing” (think “The Code Breaker”). Decisions on drug prices, an FDA commissioner, Alzheimer’s drug reimbursement, and many other aspects of health policy leading into the 2022 elections will all impact the future of orphan drug availability.  It’s a critical moment; the best of this revolution lies ahead, but is at risk if we take it for granted.

Q:  If you could have dinner with anyone past or present that you respected and admired, who would that be?

A: Thats a great question, and tough to answer. Would it be cheating to say I’d like to host a dinner party for true orphan drug pioneers like Abbey Meyers, Henry Waxman, Marlene Haffner, and Roscoe Brady to see the fruits of the revolution they started?


Jim Geraghty is national director for AI, health, and life sciences at Microsoft. In this role he works with health providers, payors, and governments in planning and implementing innovative technology solutions that improve the quality and efficiency of health services delivered around the globe. He focuses on strategies for health information modernization, business intelligence, and performance optimization. He previously served as director of organizational performance for the Microsoft Health Solutions Group.

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