What's Happening?
The FDA has rejected REGENXBIO's investigational gene therapy, RGX-121, intended for the treatment of Hunter syndrome, a rare neurodegenerative condition. The rejection was communicated through a complete
response letter (CRL), which highlighted uncertainties regarding the eligibility criteria used in the study, the use of natural history external controls, and the validity of the surrogate endpoint, specifically cerebrospinal fluid levels of the biomarker DS26. The FDA recommended conducting a new study with more patients, longer follow-up periods, and an untreated comparator group. REGENXBIO expressed that these recommendations are challenging due to the ultra-rare nature of Hunter syndrome. The gene therapy had previously been accepted into the FDA's accelerated approval program in May 2025. Despite the rejection, REGENXBIO plans to seek a Type A meeting with the FDA to discuss the path forward and provide additional evidence supporting the therapy's effectiveness.
Why It's Important?
The FDA's decision to reject RGX-121 underscores the regulatory challenges faced by companies developing treatments for rare diseases. The rejection highlights the FDA's cautious approach towards granting accelerated approvals without robust placebo-controlled data. This decision could impact other companies, such as Denali Therapeutics, which are also seeking approval for similar therapies. The rejection is a setback for REGENXBIO and the families affected by Hunter syndrome, as it delays access to potentially life-changing treatment. The decision also reflects broader regulatory trends that could influence the development and approval of gene therapies, particularly those targeting rare conditions.
What's Next?
REGENXBIO plans to engage with the FDA in a Type A meeting to discuss the next steps for RGX-121. The company aims to provide additional evidence and expert opinions to support the therapy's effectiveness. The outcome of these discussions will determine the future course of action, including the possibility of conducting a new study as recommended by the FDA. The decision also sets a precedent for other companies developing similar therapies, potentially influencing their regulatory strategies and study designs.
