The US Food and Drug Administration (FDA) has granted accelerated approval to pariglasgene brecaparvovec-opnr (Genglycos), a one-time AAV8 gene therapy, to reduce daily cornstarch intake as an adjunct to nutritional management in patients 8 years and older with glycogen storage disease type Ia (GSD1a), making it the first approved treatment for the condition.1
Announced on August 19, 2026, the approval addresses a population previously limited to lifelong dietary management, including strict cornstarch supplementation to prevent hypoglycemia. According to estimates from The Children's Fund for Glycogen Storage Disease Research, GSD1a affects approximately 600 people in the US and 6000 worldwide.
According to the FDA announcement, pariglasgene brecaparvovec-opnr is designed to deliver a functional G6PC gene to the liver, restoring the enzyme activity needed to release stored glucose during fasting. The FDA granted the application Rare Pediatric Disease Priority Review Voucher, regenerative medicine advanced therapy (RMAT), and Fast Track designations.1
“Genglycos offers these patients and their families a one-time therapy that targets the root cause of the disease,” said Megha Kaushal, MD, MSc, acting deputy director of the Center for Biologics Evaluation and Research (CBER) Office of Therapeutic Products. “This accelerated approval reflects our confidence in the clinical evidence to date and our commitment to bringing innovative treatments to patients with rare genetic diseases while we continue to gather data to confirm long-term benefit.”1
Pariglasgene brecaparvovec-opnr trial design and primary results
The accelerated approval is based on a randomized, double-blind, placebo-controlled study in patients with GSD1a, with outcomes followed over 48 weeks after dosing.1
The FDA used the accelerated approval pathway, which permits approval based on an effect on a surrogate or intermediate endpoint reasonably likely to predict clinical benefit; the agency has specified reduction in daily cornstarch intake as that surrogate, and Ultragenyx Pharmaceutical, Inc, the therapy's manufacturer, must complete additional trials to confirm effectiveness.1 Patients treated with pariglasgene brecaparvovec-opnr showed a statistically significant mean reduction from baseline in daily cornstarch intake of 31% compared with placebo, meeting the study's primary endpoint.1
The trial also assessed glucose values in the hypoglycemic range, below 70 mg/dL, as a safety-relevant measure alongside efficacy. Gene therapy in GSD1a has been an area of active investigational interest given the burden of lifelong, around-the-clock dietary management required under standard care, and this approval represents the first regulatory validation of the approach in this population.
Pariglasgene brecaparvovec-opnr safety profile and secondary outcomes
Patients treated with pariglasgene brecaparvovec-opnr also demonstrated a mean reduction from baseline of 1 cornstarch dose per day compared with placebo, the study's secondary endpoint.1 Treated patients showed a numerical mean 3% increase in the percentage of glucose values in the hypoglycemic range compared with placebo.1 Across 2 clinical studies, including the randomized trial, serious adverse reactions reported in pariglasgene brecaparvovec-opnr-treated patients included anaphylaxis, adrenal insufficiency, elevated lactate levels, and hypoglycemia.1
The most commonly reported adverse reactions were increased transaminases, nausea, headache, constipation, and hyperglycemia. Treated patients had a higher rate of hypertriglyceridemia compared with placebo-treated patients, at 29% versus 8%.1 The prescribing information carries warnings for anaphylaxis, liver toxicity, adrenal insufficiency, and risk of tumorigenicity, and the therapy should not be used during pregnancy.1
“Patients with GSD1a face possible life-threatening complications and have limited treatment options that include primarily life-long, strict dietary management,” said Karim Mikhail, B Pharm, MS, acting director of CBER. “Today's approval is a great milestone in using a gene therapy to treat this disease and improve the quality of life for people with this condition.”1
The FDA granted accelerated approval of pariglasgene brecaparvovec-opnr to Ultragenyx Pharmaceutical, Inc, with confirmatory trials required to verify clinical benefit tied to the cornstarch-reduction surrogate endpoint.1
References
The Children’s Fund for Glycogen Storage Disease Research. What Is GSD? - CureGSD. Curegsd.org. 2026. Accessed August 20, 2026. https://www.curegsd.org/what-is-gsd
