Can a Single Gene Therapy Loosen a Lifelong Eating Schedule? FDA Approves First Treatment for Glycogen Storage Disease Type Ia

For patients with glycogen storage disease type Ia, eating is not merely part of a daily routine, but a blood glucose life-support system that cannot be easily interrupted. The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ultragenyx’s one-time gene therapy Genglycos (pariglasgene brecaparvovec-opnr) for patients aged 8 years and older. It is the first therapy approved in the United States to treat the disease, with the goal of reducing daily cornstarch requirements rather than replacing the entire dietary management regimen.

This rare inherited disease is caused by a deficiency of glucose-6-phosphatase (G6PC), which prevents the liver and kidneys from properly converting stored glycogen into glucose that can be released into the bloodstream. If patients fast for too long, they may develop dangerous hypoglycemia. They therefore typically must eat frequently and take scheduled doses of slower-digesting uncooked cornstarch throughout the day; long-term metabolic imbalance may also damage multiple organs.

Genglycos uses an AAV8 viral vector to deliver a functional G6PC gene to the liver, seeking to restore the ability to release glucose during fasting. As an in vivo gene-transfer therapy, it is administered only once, but must still be accompanied by an appropriate diet. Ultragenyx told Reuters that the treatment is priced at $2.7 million per patient in the United States and is expected to become available through qualified treatment centers within 30 to 60 days after approval. The company estimates that there are approximately 1,500 to 2,500 patients nationwide.

The approval was based primarily on the Phase 3 trial NCT05139316. Registry data show that this Ultragenyx-sponsored, randomized, double-blind, placebo-controlled study enrolled 49 participants. The FDA said that after 48 weeks of follow-up, daily cornstarch intake in the treatment group had declined by a statistically significant amount compared with placebo, falling by an average of 31% from baseline, while the average number of daily doses also decreased by one.

However, reduced cornstarch intake is only a surrogate endpoint considered reasonably likely to predict clinical benefit and does not directly demonstrate improvements in patients’ long-term risk of hypoglycemia, organ complications, or impaired quality of life. The proportion of blood glucose readings below 70 mg/dL was, in fact, an average of 3 percentage points higher in the treatment group than in the placebo group. The incidence of high triglycerides was also 29%, compared with 8% in the placebo group. The FDA therefore required a confirmatory study, and Ultragenyx agreed to provide two years of clinical safety and efficacy data.

Safety considerations likewise limit how this milestone should be interpreted. Across two clinical studies, serious adverse reactions included anaphylactic shock, adrenal insufficiency, hyperlactatemia, and hypoglycemia. The label also warns of hepatotoxicity and a potential risk of tumor formation, and explicitly states that Genglycos should not be used during pregnancy. Genglycos has opened the first door toward easing patients’ lifelong dietary burden, but whether it can deliver durable clinical benefits sufficient to offset the risks of a one-time gene therapy will depend on longer-term follow-up.