FDA approves gene therapy Genglycos, first treatment targeting cause of glycogen storage disease type Ia

On August 19, FDA granted accelerated approval to Genglycos (pariglasgene brecaparvovec-opnr), the first approved gene therapy for glycogen storage disease type Ia (GSDIa) and the first treatment designed to address the underlying cause of the disease.

GSDIa results from a deficiency of glucose-6-phosphatase, an enzyme needed for the liver to release glucose into the bloodstream. Without it, fasting can cause severe, potentially life-threatening hypoglycemia. Patients typically rely on frequent doses of raw cornstarch throughout the day and night to maintain glucose levels.

“Day-to-day management of GSDIa requires a relentless regimen of raw cornstarch and strict dietary management that can be extraordinarily demanding for patients and families,” said David Weinstein, MD, MMSc, a GSDIa expert. “Any missed cornstarch puts patients at risk of severe hypoglycemia, seizures, and even death.”

Genglycos is a one-time gene therapy that uses an engineered viral vector to deliver a functional copy of the G6PC gene to liver cells, aiming to restore the liver’s ability to release glucose into the bloodstream during fasting. The FDA-approved indication is specifically to reduce daily cornstarch intake as an adjunct to nutritional management in adults and children aged eight years and older with GSDIa.

Approval was based on the phase 3 GlucoGene trial, which randomized 46 patients to Genglycos or placebo. At 48 weeks, Genglycos significantly reduced cornstarch requirements compared with placebo, the endpoint supporting accelerated approval. Continued approval may depend on confirmation of clinical benefit in postmarketing follow-up.

The treatment introduces new considerations for clinicians beyond routine GSDIa management. Genglycos is contraindicated in patients with severe hepatic fibrosis or cirrhosis and should be avoided in those with preexisting hepatic impairment or acute viral hepatitis. Immune-mediated hepatotoxicity can occur, requiring corticosteroids after infusion and transaminase monitoring for the first six months. Serious infusion reactions, including anaphylaxis, and adrenal insufficiency during corticosteroid treatment or tapering have also been reported. Genglycos will be administered through specialized gene therapy treatment centers.

“For families affected by GSDIa, every day revolves around strict schedules, overnight vigilance, and the constant worry that a missed meal or dose of cornstarch could trigger life-threatening hypoglycemia,” said David and Wendy Feldman, co-founders of The Children’s Fund for Glycogen Storage Disease Research. “This approval is an incredibly meaningful milestone for a community that has spent decades hoping, advocating, and helping advance the research for new treatment options that could ease the burdens of this disease.”

Source: Ultragenyx. (2026 Aug 19). Ultragenyx Announces U.S. FDA Approval of GENGLYCOS Gene Therapy, the First-Ever FDA-Approved Treatment Designed to Treat the Underlying Cause of Glycogen Storage Disease Type Ia (GSDIa)