2 Regenxbio Gene Therapies Get Clinical Holds

FDA has placed clinical holds on two Regenxbio investigational gene therapy programs for ultra-rare pediatric diseases following the identification of a central nervous system tumor in a single patient treated with one of its candidates. A hold was placed on RGX-111, an experimental gene therapy for mucopolysaccharidosis Type I (MPS I), also known as Hurler syndrome, after a preliminary review of a case of neoplasm detected in a participant enrolled in a Phase 1/2 study, the company says. The agency also placed a hold on RGX-121, a separate gene therapy program for mucopolysaccharidosis Type II (MPS II or Hunter syndrome), citing similarities between the products, study populations and potential shared risks.

The tumor was identified during a routine brain MRI in an asymptomatic five-year-old child who received intracisternal RGX-111 about four years ago. According to Regenxbio, preliminary genetic analysis of the resected tumor identified an adeno-associated virus (AAV) vector genome integration event associated with overexpression of the proto-oncogene PLAG1, a gene known to be susceptible to chromosomal rearrangements. The company said the investigation into whether the serious adverse event is related to RGX-111 is ongoing and that causality has not been established.

Regenxbio says the affected participant remains asymptomatic, with positive developmental progress reported by the treating physician. No cases of neoplasm have been observed in the nine other patients treated with RGX-111 or in the 32 patients who have received RGX-121 to date, it says.

“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 President and chief executive officer Curran Simpson is quoted in a release as saying. He added that RGX-121 has shown a favorable safety profile in more than 30 patients, including some treated nearly seven years ago, and that the company remains confident in the benefit-risk profile of the therapy.

RGX-111 is an AAV9-based gene therapy intended to deliver the alpha-L-iduronidase gene to the central nervous system in patients with MPS I, with the goal of preventing or slowing cognitive decline, according to the company. RGX-121, also known as clemidsogene lanparvovec, is being developed as a potential one-time gene therapy for boys with MPS II and is designed to deliver the iduronate-2-sulfatase gene to the central nervous system to address the neurological manifestations of the disease.

Both MPS I and MPS II are rare, inherited lysosomal storage disorders that cause progressive, multisystem disease, including severe neurological impairment in their most serious forms, the company says.