A central nervous system (CNS) tumor has prompted the FDA to place clinical holds on two Regenxbio gene therapies, including a candidate that is less than two weeks away from an approval decision. Regenxbio’s share price fell 32% to $9.16 in premarket trading.
Regenxbio said the abnormal growth was found in a recipient of RGX-111, a gene therapy the company is developing for the treatment of severe mucopolysaccharidosis type I (MPS I). Also known as Hurler syndrome, the rare disease can cause developmental delays and shorten life span. RGX-111 is designed to improve outcomes by using an AAV9 vector to deliver the IDUA gene to the CNS.
While the adverse event occurred in a recipient of RGX-111, the FDA extended the clinical hold to cover RGX-121 because of similarities between the therapies, trial populations and shared risks of the studies. RGX-121 is designed to treat MPS II, also known as Hunter syndrome. Last August, the FDA delayed an approval decision for the latter, with a new verdict expected by Feb. 8.
“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," Regenxbio CEO Curran Simpson said in a statement. “These are separate therapies, and the positive safety profile of RGX-121 in more than 30 patients treated, including those dosed nearly seven years ago, remains unchanged.”
Regenxbio deprioritized RGX-111 in 2023, starting a search for a partner that led to a deal with Nippon Shinyaku one year ago. The biotech continued to invest in RGX-121, which was also part of the Nippon Shinyaku deal, and filed for FDA approval of the therapy last year.
The holds were triggered by the discovery of a neoplasm, which Regenxbio called an intraventricular CNS tumor, during a routine MRI of an asymptomatic 5-year-old. The patient had received a delivery of RGX-111 into a space near the brain four years earlier.
Preliminary genetic analysis of the resected brain tumor found an AAV vector genome integration event. The event was associated with overexpression of PLAG1, a proto-oncogene susceptible to chromosomal rearrangements. An investigation into whether the serious adverse event is related to RGX-111 is ongoing.
Regenxbio said the patient remains asymptomatic, adding that the treating physician has noted positive developmental advancements. There is no evidence of neoplasm in the other nine recipients of RGX-111.