During a regulatory forum on Thursday, gene therapy experts and advocates voiced serious concerns about the field’s challenges to FDA leadership, even as remarkable scientific advances continue to demonstrate the technology’s potential.
The meeting came in the same week that 10-month-old KJ Muldoon was discharged from a Philadelphia hospital after receiving a customized CRISPR treatment for a rare liver condition called CSP1 deficiency. While not completely cured, the treatment has allowed KJ to return to a normal diet, with doctors reducing supportive medications and expressing optimism that a liver transplant may no longer be necessary.
CRISPR scientist David Liu highlighted at the FDA meeting that approximately 10 million infants are born annually with one of roughly 10,000 known rare genetic diseases, many of which could potentially be treated with genetic medicines. However, the 23 experts and advocates present weren’t there to celebrate successes – they came to discuss an industry in crisis.
Despite dozens of approved cell and gene therapies in the United States offering transformative treatment potential for conditions like spinal muscular atrophy and sickle cell disease, the sector faces significant headwinds. Investment has declined as companies struggle with profitability challenges for these complex, expensive treatments. This has led to research cuts, workforce reductions, and some business closures. Major pharmaceutical companies are increasingly hesitant to invest billions in overcoming regulatory and reimbursement obstacles.
According to Terence Flotte, dean of UMass T.H. Chan School of Medicine and ASCGT president, over 100 rare disease gene therapy products in clinical development have been discontinued since 2023 due to market viability concerns rather than treatment ineffectiveness. Stanford University’s Crystal Mackall emphasized that despite “spectacular” scientific progress, the field struggles to deliver treatments to all eligible patients.
FDA leadership, including Commissioner Martin Makary and cell and gene therapy office head Vinay Prasad, expressed support for the field’s concerns. Makary committed to improving regulatory efficiencies while maintaining facilitation of the approval process. Prasad acknowledged that transformative results aren’t always immediate and expressed openness to incremental advances.
Experts proposed various solutions during the meeting. Penn
immunologist Carl June suggested adopting elements of China’s two-tier regulatory system to expedite first-in-human trials. UCLA’s Don Kohn requested reduced comparability testing requirements when
transitioning from academic to commercial production. Others emphasized the importance of regulatory incentives like priority review vouchers and called for increased sharing of FDA feedback.
A common thread throughout the discussion was concern about
maintaining U.S. leadership in developing curative treatments. June warned that without adaptation, the next generation of treatments would emerge from other countries, putting “the future of medicine with cell and gene therapy” at stake.
The FDA officials appeared receptive to these concerns. Prasad indicated plans to make more internal documents available to help developers understand agency requirements. Makary emphasized the meeting’s purpose as “an honest listening session” rather than a perfunctory exercise.
The discussion highlighted the paradox facing genetic medicine: while scientific capabilities for treating rare diseases continue to advance, as demonstrated by cases like KJ Muldoon’s, the industry’s ability to bring these treatments to market faces mounting challenges that threaten to impede progress unless regulatory and economic hurdles can be addressed.