The U.S. Food and Drug Administration has approved the first treatment for glycogen storage disease type Ia, a rare inherited disorder that can cause dangerously low blood sugar and long-term metabolic complications.

The FDA granted accelerated approval to Genglycos (pariglasgene brecaparvovec-opnr), a one-time gene therapy from Ultragenyx Pharmaceutical Inc., a news release said. The therapy is approved for adults and pediatric patients 8 years and older to reduce daily cornstarch intake as an adjunct to nutritional management.

GSDIa is caused by a genetic mutation that leaves the body deficient in glucose-6-phosphatase, or G6PC. The enzyme normally helps the liver and kidneys release free glucose into the bloodstream, maintaining stable blood sugar levels during fasting and between meals.

Without enough G6PC, blood sugar can fall to dangerously low levels when a person goes too long without eating. The disease can also cause long-term metabolic complications that impair the normal function of certain organs and tissues.

Treatment typically requires careful medical monitoring, frequent meals, avoidance of certain foods containing simple sugars and strict, around-the-clock dietary supplementation with uncooked or specially formulated cornstarch. The slow-digesting complex carbohydrate helps prevent hypoglycemia, or abnormally low blood sugar.

“Patients with GSDIa face possible life-threatening complications and have limited treatment options that include primarily life-long, strict dietary management,” said Karim Mikhail, B. Pharm., M.S., acting director of the Center for Biologics Evaluation and Research, in teh release. “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.”

Genglycos uses an adeno-associated virus serotype 8, or AAV8, to deliver a functional G6PC gene to the liver. The one-time treatment is designed to restore the deficient enzyme, allowing the body to release stored glucose and maintain stable blood sugar levels during fasting.

“Genglycos offers these patients and their families a one-time therapy that targets the root cause of the disease,” said Megha Kaushal, M.D., MSc., acting deputy director of the 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.”

The FDA's accelerated approval pathway allows the agency to approve certain drugs or biologics intended to treat serious or life-threatening diseases when a treatment demonstrates an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit.

For Genglycos, the FDA based its accelerated approval on clinical trial data showing the therapy reduced patients' daily cornstarch intake when used with an appropriate diet. The reduction in cornstarch intake served as the surrogate endpoint. Ultragenyx must conduct additional clinical trials to confirm the therapy's effectiveness.

Genglycos was evaluated in a randomized, double-blind, placebo-controlled study that followed patients with GSDIa for 48 weeks after dosing. Patients who received Genglycos had a statistically significant mean reduction of 31% from baseline in daily cornstarch intake compared with placebo, meeting the study's primary endpoint.

The Genglycos group also had a mean reduction of one cornstarch dose per day compared with placebo, which was the study's secondary endpoint.

However, patients treated with Genglycos experienced a numerical mean increase of 3% in the percentage of glucose values in the hypoglycemic range, defined as less than 70 mg/dL, compared with placebo.

Across two clinical studies of Genglycos, including the randomized study, serious adverse reactions among treated patients included anaphylaxis, adrenal insufficiency, high lactate levels and hypoglycemia.

The most commonly reported adverse reactions included elevated transaminases, or liver enzymes, nausea, headache, constipation and hyperglycemia.

Genglycos-treated patients also had a higher rate of hypertriglyceridemia, or elevated blood triglyceride levels, than patients who received placebo, at 29% compared with 8%. Hypertriglyceridemia is a metabolic marker associated with GSDIa.

The prescribing information includes warnings about anaphylaxis, liver toxicity, adrenal insufficiency and tumorigenicity, or the development of tumors. Genglycos should not be used during pregnancy.

The therapy received a Rare Pediatric Disease Priority Review Voucher. The FDA also granted Genglycos regenerative medicine advanced therapy, or RMAT, and Fast Track designations.

The FDA's approval makes Genglycos the first approved treatment for GSDIa and provides a new therapeutic option for children and adults living with the rare genetic disorder.