REGENXBIO Inc. stock tumbled 28% Wednesday after the U.S. Food and Drug Administration placed clinical holds on two of the company's investigational gene therapies intended to treat ultra-rare pediatric genetic disorders.
The regulatory move follows the discovery of a tumor in the brain of a five-year-old patient who had received the company's RGX-111 therapy for MPS I (Hurler syndrome) four years earlier. In response to that finding, the FDA also placed a hold on trials of RGX-121, which is being developed for MPS II (Hunter syndrome), citing perceived similarities between the products and their patient populations.
REGENXBIO said preliminary genetic analysis of the tumor identified an AAV vector genome integration event that was associated with overexpression of a proto-oncogene known as PLAG1. The company emphasized that investigators have not established causality between the therapy and the tumor, and noted that the affected patient remains asymptomatic and is showing positive developmental progress.
In a statement, Curran Simpson, President and CEO of REGENXBIO, expressed surprise at the FDA's decision to place the RGX-121 program on hold while the company continues to investigate what it describes as a single, inconclusive incident in RGX-111. "We are surprised by FDA's decision to place our RGX-121 program on hold while the investigation of this single, inconclusive incident in RGX-111 continues," the company quoted Simpson as saying.
The company also highlighted that the two therapies are separate, and that RGX-121 has shown a positive safety profile in more than 30 patients treated, including people dosed nearly seven years ago. REGENXBIO reported that among other participants there has been no evidence of neoplasm in nine additional patients treated with RGX-111 or in the 32 participants who received RGX-121.
REGENXBIO is awaiting receipt of the full clinical hold letter from the FDA for additional specifics on the agency's rationale and any required next steps. The company has not indicated any other new safety signals beyond the single tumor discovery and the preliminary genetic findings.
The clinical holds represent a substantial setback for the company's development programs directed at MPS I and MPS II - ultra-rare disorders that cause progressive neurodevelopmental decline in affected children. The holds will pause ongoing clinical activity for both programs until the FDA and the company have resolved outstanding safety questions.
Context and next steps
At this point, information available is limited to the FDA's placed holds, the tumor discovery in the one patient treated with RGX-111, the preliminary genetic analysis linking an integration event to PLAG1 overexpression, and REGENXBIO's statements regarding the absence of neoplasm findings in other trial participants. The company is awaiting further documentation from the agency that is expected to clarify the scope of the holds and any required investigational measures.