FDA Grants Accelerated Approval to Ultragenyx's Genglycos, First Gene Therapy for Glycogen Storage Disease Type Ia

The FDA has granted accelerated approval to pariglasgene brecaparvovec-opnr (Genglycos) for adults and pediatric patients eight years of age and older with glycogen storage disease type Ia (GSDIa), a rare inherited disorder caused by deficiency of the enzyme glucose-6-phosphatase.¹ Genglycos, formerly known in development as DTX401, is indicated to reduce daily cornstarch intake as an adjunct to nutritional management and is the first approved therapy for the condition.¹^,²

How does the therapy work?

Genglycos is a one-time, AAV8-based gene therapy administered as a single intravenous infusion, designed to deliver a functional G6PC gene to liver cells to restore glucose-6-phosphatase activity and stabilize blood sugar during fasting.¹^,⁵ GSDIa patients currently manage the disease primarily through strict, around-the-clock dietary cornstarch supplementation to prevent dangerous drops in blood sugar.¹ "Current dietary approaches to managing GSDIa place an extraordinary burden on individuals and families while still leaving patients with significant medical needs, including the risk of potentially life-threatening episodes of acute hypoglycemia and accumulation of long-term complications over their lifetime," said Eric Crombez, MD, chief medical officer at Ultragenyx, when the BLA was accepted for review in February 2026.⁶

What clinical evidence supported the approval?

The accelerated approval rests on a randomized, double-blind, placebo-controlled study following patients over 48 weeks after dosing.¹ Genglycos-treated patients showed a statistically significant mean 31% reduction from baseline in daily cornstarch intake compared with placebo, the study's primary endpoint, along with a mean reduction of one cornstarch dose per day, the secondary endpoint.¹ Because this is an accelerated approval, reduced cornstarch intake serves as a surrogate endpoint, and Ultragenyx must complete additional trials to confirm clinical benefit.¹ "The approval of Genglycos fulfills our commitment to provide the first therapy that directly targets the root cause of GSDIa," Crombez said, adding that the therapy's ability to regulate glucose "has the potential to mitigate the risk of severe or life-threatening hypoglycemia for these patients."³

What safety concerns come with the therapy?

Serious adverse reactions reported across two clinical studies included anaphylaxis, adrenal insufficiency, elevated lactate levels, and hypoglycemia, and the most common adverse reactions were increased liver transaminases, nausea, headache, constipation, and hyperglycemia.¹ Genglycos-treated patients also showed a higher rate of hypertriglyceridemia than placebo-treated patients (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 "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," said Karim Mikhail, B Pharm, MS, acting director of the FDA's Center for Biologics Evaluation and Research.¹

What's next for patients and for Ultragenyx?

GSDIa affects an estimated 6,000 people in commercially accessible regions globally, according to a company-sourced estimate.⁴ The approval carries regenerative medicine advanced therapy and Fast Track designations, and the application received a Rare Pediatric Disease Priority Review Voucher.¹ Because accelerated approval is contingent on confirmatory data, Ultragenyx's continued trials evaluating durability of response will determine whether Genglycos retains full approval over the long term.

References

1. FDA approves first therapy for patients aged 8 years and older with glycogen storage disease type Ia. News release. US Food and Drug Administration. Published August 19, 2026. Accessed August 20, 2026.
2. DTX401 (pariglasgene brecaparvovec) drug history. Drugs.com. Accessed August 20, 2026.
3. 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). News release. Ultragenyx Pharmaceutical Inc. Published August 19, 2026. Accessed August 20, 2026.
4. RARE rises on completion of rolling submission for AAV gene therapy. Zacks Investment Research. Published via Nasdaq.com. Accessed August 20, 2026.
5. What are new potential treatments in glycogen storage disease type Ia? Drugs.com. Published March 16, 2026. Accessed August 20, 2026.
6. Ultragenyx announces US FDA acceptance and priority review of the biologics license application (BLA) for DTX401 AAV gene therapy for glycogen storage disease type Ia (GSDIa). News release. Ultragenyx Pharmaceutical Inc. Published February 23, 2026. Accessed August 20, 2026.