Regulatory & Policy

FDA approves Genglycos as first gene therapy for glycogen storage disease type Ia

Edited by Robert McTiernan··2 min read
FDA approves Genglycos as first gene therapy for glycogen storage disease type Ia

The US FDA has granted accelerated approval for Genglycos (pariglasgene brecaparvovec-opnr), an AAV8 gene therapy developed by Novato, California-based Ultragenyx Pharmaceutical (Nasdaq: RARE), making it the first approved treatment targeting the underlying cause of glycogen storage disease type Ia (GSDIa). The approval marks Ultragenyx's fifth FDA-approved product and its first gene therapy, and was accompanied by a Priority Review Voucher.

Genglycos is indicated to reduce daily cornstarch intake as an adjunct to nutritional management in adult and pediatric patients aged 8 years and older with GSDIa. The accelerated approval is notable for its reliance on reduced cornstarch intake as the surrogate endpoint rather than a traditional clinical outcome. Patients with GSDIa require frequent cornstarch supplementation to maintain blood glucose because G6PC deficiency prevents normal hepatic glucose release. A sustained reduction in cornstarch requirements therefore provides evidence that Genglycos is restoring some endogenous glucose regulation, although the FDA is requiring confirmatory follow-up to verify longer-term clinical benefit. Ultragenyx has agreed to provide two years of safety and efficacy data from open-label commercial treatment of 50 patients and 20 controls through an enhanced GSDIa Disease Monitoring Program (DMP), with 10-year follow-up planned. Administration is restricted to a national network of Qualified Treatment Centers, and the therapy is manufactured entirely at Ultragenyx's Gene Therapy Manufacturing Facility in Bedford, Massachusetts.

The Phase III GlucoGene study, as previously reported, enrolled 46 participants aged 8 years and older in a randomized, double-blind, placebo-controlled design. In the modified intention-to-treat population of 44 participants, treatment with Genglycos (pariglasgene brecaparvovec-opnr) at 1.0 x 10¹³ GC/kg produced a statistically significant reduction in cornstarch requirements at Week 48 compared with placebo (p<0.001). Participants who completed the 48-week primary period crossed over to the alternate treatment, with follow-up analyses at Weeks 96 and 144.

The AllSci BriefSystematic R&D and deal news. Daily.

Genglycos delivers a functional copy of the G6PC gene encoding glucose-6-phosphatase-α via a recombinant, non-replicating AAV8 vector under a liver-specific promoter, restoring the enzymatic capacity for hepatic glucose release from a single intravenous administration. This approach directly addresses the enzyme deficiency underlying GSDIa, in contrast to cornstarch supplementation, which provides only an exogenous glucose source without correcting the metabolic defect.

Prior to this approval, no pharmacological treatment existed for GSDIa; management relied entirely on continuous dietary cornstarch supplementation. A notable clinical-stage competitor is BEAM-301, an in vivo base-editing program from Beam Therapeutics (Nasdaq: BEAM) that uses lipid nanoparticle delivery to correct the R83C G6PC point mutation — the most prevalent GSDIa variant — and is currently in Phase I/II evaluation (NCT06735755). Unlike Genglycos, which adds a functional gene copy regardless of variant, BEAM-301 targets a specific mutation, a distinction that will define their respective eligible populations.

Spot something wrong? Report an issue with this article