REGENXBIO Receives FDA CRL for RGX-121 over Data and Endpoint Gaps
REGENXBIO’s BLA for RGX-121 received a complete response letter citing uncertainty in patient eligibility criteria, external control data comparability, and validity of CSF HS D2S6 as a surrogate endpoint. The company will seek a Type A meeting, provide additional clinical evidence and expert analyses, and aim to resubmit promptly.
1. FDA Issues Complete Response Letter
FDA issued a complete response letter for RGX-121’s biologics license application, recognizing the accelerated approval intention but withholding approval pending resolution of critical data gaps and surrogate endpoint validation.
2. Identified Trial and Endpoint Concerns
The letter cited three primary concerns: uncertainties in defining neuronopathic versus attenuated MPS II populations, lack of comparability between external natural history control data and study cohorts, and questions over CSF HS D2S6 as a surrogate endpoint predictive of clinical benefit.
3. Planned Regulatory Engagement
REGENXBIO plans to request a Type A meeting to align on next steps, discussing proposed new studies, extended follow-up of additional patients, or incorporation of an untreated control arm.
4. Strategic Resubmission Approach
The company intends to compile further evidence from global MPS II experts, bolster long-term clinical follow-up data, and aim for a prompt resubmission of the BLA under the accelerated approval framework.