KEY POINTS
- The U.S. Food and Drug Administration declined to approve Regenxbio’s RGX-121 gene therapy for Hunter syndrome.
- The FDA’s complete response letter flagged uncertainty over trial design and surrogate endpoints.
- Regenxbio shares dropped sharply after the regulatory setback and the company plans further talks.
The U.S. Food and Drug Administration has opted not to approve Regenxbio Inc’s experimental gene therapy RGX-121 for Hunter syndrome, a rare neurodegenerative disorder mainly affecting boys.
In a complete response letter issued on Monday, the FDA outlined concerns about the design of the clinical trial. The regulator questioned whether the eligibility criteria and the surrogate endpoint chosen could reliably predict meaningful clinical benefit.
Hunter syndrome, also known as mucopolysaccharidosis II, is an ultra-rare inherited disorder in which the body cannot properly break down complex sugar molecules. Affected children often suffer progressive physical and cognitive decline.
RGX-121 is a one-time gene therapy intended to deliver a functional gene to help break down these molecules. The treatment had been under review for accelerated approval because of the severe and irreversible nature of the disease.
Regulators had already placed the program on clinical hold earlier in 2026, along with another Regenxbio rare disease therapy, following safety questions.
The FDA’s refusal to approve marks a significant regulatory setback for the company, which has been developing RGX-121 for more than a decade. The decision underscores challenges in evaluating potential therapies for very small patient populations.
Investors reacted swiftly, sending Regenxbio’s stock down sharply in after-hours trading as market participants absorbed the news.
Regenxbio acknowledged the difficulty of conducting larger or longer follow-up studies in an ultra-rare disease group. The company said it plans to request a meeting with the FDA to discuss potential resubmission and how to provide additional clinical evidence.
The complete response letter did not reference specific safety issues with RGX-121 but focused on the strength of the clinical evidence and how study results can be linked to patient outcomes.
Regenxbio’s leadership expressed concern about the regulator’s feedback, noting the pressing need for new treatment options for families affected by Hunter syndrome.
The company intends to evaluate possible pathways forward, including expanded global studies, extended patient follow-up and exploring alternative endpoints that satisfy regulatory expectations.
If the therapy had gained approval, it could have offered a novel one-time treatment for a debilitating condition with few existing options. The setback highlights broader issues in bringing advanced genetic therapies to market for rare diseases.
Patient advocacy groups and families awaiting breakthroughs for Hunter syndrome may view the FDA’s decision with disappointment, as development of new therapies moves cautiously through regulatory scrutiny.
Regenxbio’s announcement comes amid a broader context of regulatory activity in rare disease drug evaluations, with varying decisions from U.S. regulators affecting clinical pipelines industry-wide.
