The FDA must provide consistent and predictable regulatory frameworks if the U.S. is to maintain its leadership in gene therapy, one of the most consequential therapeutic fields of our generation.
The resignation of FDA Commissioner Marty Makary on May 12 was the latest disruption in what has been a difficult period for the rare disease and gene therapy communities. For families living with devastating genetic conditions, and for innovators working to develop these transformative therapies, it is one more reminder that predictability at the FDA is not a bureaucratic nicety. It is a lifeline.
From my time on the House Ways and Means Committee, and now as chairman of the Institute for Gene Therapies, I have watched the promise of gene therapy evolve from scientific aspiration into clinical reality. I have met patients and families for whom these transformative treatments represent the only realistic hope of a meaningful life. And I have watched with growing concern as the regulatory environment that should be enabling this field has instead become a source of uncertainty and instability.
Makary appeared to have genuine ambitions. The plausible mechanism framework for individualized gene therapies, introduced in collaboration with former Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad, was a thoughtful attempt to acknowledge and address what the gene therapy field has long understood: that the traditional clinical trial infrastructure was not designed for ultrarare diseases. The framework sought to allow data from small patient populations to support broader approvals by targeting specific genetic, cellular or molecular abnormalities. That was meaningful progress, and it deserves credit.
But progress announced in guidance documents does not become a regulatory reality on its own. Even as new pathways were unveiled, rare disease rejection rates climbed sharply. Analysts tracking CBER decisions in early 2026 noted rejection rates for orphan products approaching 30%, compared to approximately 10% in prior years.
Predictability at the FDA is not a bureaucratic nicety. It is a lifeline.
In addition to small patient populations, manufacturing complexity and lengthy development timelines make investment decisions in this space extraordinarily sensitive to regulatory risk. As a result, that kind of inconsistency is more than frustrating for gene therapy developers. It can end programs before patients ever have the chance to benefit.
The gene therapy pipeline is not self-sustaining. It depends on investment decisions made years before a single patient is dosed, and those decisions are made against a backdrop of regulatory signals. When those signals are unclear or contradictory, capital flows to programs with more predictable paths, and sometimes to programs in other countries, where regulators have been quietly and methodically building frameworks for advanced therapies.
Today, the U.S. leads the world in biomedical innovation. Continuation of this leadership is not guaranteed, and it will not survive regulatory uncertainty in one of the most consequential therapeutic fields of our generation.
The good news is that support for advancing gene therapies is a genuinely bipartisan cause. Pediatric priority review vouchers, the Accelerating Kids’ Access to Care Act and legislative frameworks supporting rare disease development have all moved forward with backing from both sides of the aisle. The next FDA commissioner should reflect that same bipartisan commitment to more effectively put patients above politics.
Setting the stage for success
As the search for a permanent FDA commissioner begins, those of us who are committed to advancing gene therapy have both an opportunity and an obligation to define what the field needs.
We need a commissioner who genuinely centers the patient perspective. Gene therapies exist because patients with serious, often fatal genetic conditions have no other option. The evidence frameworks, flexible pathways and adaptive trial designs that this field requires are not concessions to industry. They are the appropriate scientific response to the patient populations faced with these rare and ultrarare diseases.
We need a commissioner who understands the economics of innovation. Drug development investment follows predictability. Investors and developers need to know that a well-designed program, supported by a scientifically sound evidence package and developed in good-faith alignment with FDA guidance, will receive a fair and consistent review.
We need a commissioner who is fluent in the evidence tools available for rare disease: adaptive and innovative trial designs, natural history data, real-world evidence, patient-reported outcomes and biomarker science. These are not shortcuts. They are the legitimate evidentiary methods appropriate to diseases where randomized controlled trials of traditional scale are simply not possible.
And we need a commissioner who will commit to building a durable, practical framework for gene therapy regulation—grounded in science, developed in collaboration with patients, developers and clinicians, and designed to outlast any single administration’s priorities.
The Institute for Gene Therapies stands ready to engage—with policymakers, with the acting and incoming commissioners and with the full stakeholder community—in order to advance the practical frameworks that will determine whether the next generation of gene therapies reaches patients in the U.S.
The science is ready. The patients are waiting. We now need FDA leadership that is committed to bringing vision and stability that can close this gap and cement a foundation for breakthrough innovations like gene therapy.
