According to a new announcement, the FDA has granted accelerated approval to pariglasgene brecaparvovec-opnr (Genglycos; Ultragenyx Pharmaceutical, Inc), a one-time, liver-directed 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).1 The approval, announced August 19, 2026, makes pariglasgene brecaparvovec-opnr the first approved treatment for GSD1a.1
"Patients with GSD1a face possible life-threatening complications and have limited treatment options that include primarily life-long, strict dietary management," Karim Mikhail, B Pharm, MS, acting director of CBER, said in a statement. "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
Pariglasgene brecaparvovec-opnr trial design and primary results in GSD1a
The therapy delivers a functional G6PC gene to the liver to restore glucose-6-phosphatase activity, targeting the enzymatic defect underlying impaired fasting glucose homeostasis in GSD1a.1 FDA granted the application Rare Pediatric Disease Priority Review Voucher, regenerative medicine advanced therapy, and Fast Track designations.1 According to estimates from The Children's Fund for Glycogen Storage Disease Research, GSD1a affects approximately 600 people in the US and 6000 worldwide.2
The accelerated approval is based on a randomized, double-blind, placebo-controlled trial with outcomes followed over 48 weeks after dosing.1 FDA used the accelerated approval pathway, permitting approval based on an effect on a surrogate endpoint reasonably likely to predict clinical benefit; the agency specified reduction in daily cornstarch intake as that surrogate.1 Patients treated with pariglasgene brecaparvovec-opnr showed a statistically significant mean 31% reduction from baseline in daily cornstarch intake compared with placebo, meeting the primary endpoint.1
Pariglasgene brecaparvovec-opnr safety and secondary outcomes
Frequently Asked Questions
What is pariglasgene brecaparvovec-opnr approved for?
Pariglasgene brecaparvovec-opnr (Genglycos) is approved to reduce daily cornstarch intake as an adjunct to nutritional management in patients 8 years and older with GSD1a.
How does pariglasgene brecaparvovec-opnr work?
It is a one-time, liver-directed AAV8 gene therapy that delivers a functional G6PC gene to restore glucose-6-phosphatase activity and stabilize blood glucose during fasting.
What did the pivotal trial show?
In a randomized, double-blind, placebo-controlled trial, treated patients had a statistically significant 31% mean reduction from baseline in daily cornstarch intake compared with placebo at 48 weeks.
Treated patients also showed a mean reduction from baseline of one cornstarch dose per day compared with placebo, the secondary endpoint.1 Treated patients showed a numerical mean 3% increase in the percentage of glucose values in the hypoglycemic range, below 70 mg/dL, compared with placebo.1 Across 2 clinical studies, including the randomized trial, serious adverse reactions in 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.1 Treated patients had a higher rate of hypertriglyceridemia compared with placebo, at 29% versus 8%.1 The prescribing information carries warnings for anaphylaxis, liver toxicity, adrenal insufficiency, and tumorigenicity risk, and the therapy should not be used during pregnancy.1
"Genglycos offers these patients and their families a one-time therapy that targets the root cause of the disease," Megha Kaushal, MD, MSc, acting deputy director of the FDA Center for Biologics Evaluation and Research (CBER) Office of Therapeutic Products, said in a statement. "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
Confirmatory trials are required of Ultragenyx Pharmaceutical to verify clinical benefit tied to the cornstarch-reduction surrogate endpoint, standard practice under the accelerated approval pathway for rare genetic disease gene therapies.1
References
FDA approves first therapy for patients aged 8 years and older with glycogen storage disease type Ia. FDA. Published August 19, 2026. Accessed August 20, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-aged-8-years-and-older-glycogen-storage-disease-type-ia
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
