REGENXBIO (NASDAQ:RGNX) saw its shares tumble 27% after the U.S. Food and Drug Administration issued a Complete Response Letter (CRL) rejecting its gene therapy candidate RGX-121 for the treatment of Mucopolysaccharidosis II (MPS II), commonly known as Hunter syndrome.
The February 7 CRL identified a set of regulatory concerns that led to the decision. The agency highlighted uncertainty around the trial's eligibility criteria, raised questions about whether the natural history control groups used in analyses were sufficiently comparable, and flagged the appropriateness of the surrogate endpoint that REGENXBIO used to predict clinical benefit.
These regulatory findings stand in contrast to the FDA's prior procedural acceptance of the company's Biologics License Application under the accelerated approval pathway in May 2025. Despite that earlier acceptance, the CRL indicates the agency concluded the available evidence and study design did not support approval at this time.
In response to the letter, REGENXBIO said it would seek a Type A meeting with the FDA to discuss the contents of the CRL and outline a path forward for a potential BLA resubmission. The company intends to present additional evidence from global MPS II experts to more clearly define the neuronopathic patient population and to submit longer-term clinical data to bolster the case that RGX-121 can meaningfully alter the course of Hunter syndrome.
REGENXBIO’s President and CEO Curran Simpson described the agency's decision as "devastating for the families of boys living with this progressive, life-threatening disease." The company noted its concern about the feedback on development pathway and data evaluation, particularly given the urgent need for therapies for this ultra-rare condition.
MPS II is a rare, neurodegenerative disorder that causes irreversible brain damage and typically leads to premature death, usually in patients' mid-teens. The National MPS Society expressed disappointment with the FDA’s decision, emphasizing that families have been waiting 20 years for new treatment options.
REGENXBIO has been developing RGX-121 for over 10 years and said it remains confident in the evidence supporting the therapy’s potential to positively change the trajectory of Hunter syndrome. The company’s next steps will focus on regulatory engagement and additional data collection in hopes of addressing the issues cited in the CRL.
Summary
The FDA issued a Complete Response Letter on February 7 rejecting REGENXBIO’s RGX-121 for MPS II, citing concerns about study eligibility, natural history control comparability, and the surrogate endpoint. REGENXBIO plans to seek a Type A meeting and provide additional expert and longer-term data to support a resubmission. The decision triggered a 27% drop in the company's stock.
Key points
- Regulatory action - The FDA issued a CRL outlining specific concerns about the BLA for RGX-121.
- Clinical evidence and design - The agency questioned eligibility criteria, control comparability, and the surrogate endpoint used to predict benefit.
- Market impact - The announcement led to a 27% decline in REGENXBIO’s share price and has implications for biotech and healthcare investors evaluating gene therapies for ultra-rare diseases.
Risks and uncertainties
- Regulatory risk - The CRL identifies clear hurdles that must be resolved before the FDA would consider approval, affecting the drug development timeline.
- Data sufficiency - Questions about control group comparability and surrogate endpoints indicate uncertainty about whether existing evidence will be adequate to secure approval.
- Commercial and patient access uncertainty - The rejection delays potential availability of a treatment for an ultra-rare, life-threatening condition, with consequences for patients, families, and stakeholders in rare-disease therapeutics.