The US Food and Drug Administration granted accelerated approval to pariglasgene brecaparvovec-opnr (Genglycos) to reduce daily cornstarch intake as an adjunct to nutritional management in patients aged 8 years and older with glycogen storage disease type Ia. It is the first approved treatment for the condition.
Glycogen storage disease type Ia is a rare inherited disorder caused by glucose-6-phosphatase deficiency. The enzyme normally enables the liver and kidneys to release glucose into the bloodstream during fasting and between meals. The deficiency can cause hypoglycemia when patients go too long without eating and lead to long-term metabolic complications affecting organs and tissues.
Management of glycogen storage disease type Ia includes medical monitoring, frequent meals, avoidance of certain foods containing simple sugars, and around-the-clock supplementation with uncooked or specially formulated cornstarch to prevent hypoglycemia. Pariglasgene brecaparvovec-opnr is a one-time adeno-associated virus serotype 8-based gene therapy designed to deliver a functional glucose-6-phosphatase gene to the liver.
The US Food and Drug Administration based the accelerated approval on clinical trial data, including findings from a randomized, double-blind, placebo-controlled study that followed patients for 48 weeks after dosing. Patients treated with pariglasgene brecaparvovec-opnr had a statistically significant 31% mean reduction from baseline in daily cornstarch intake compared with placebo, the primary endpoint. Treated patients also had a mean decrease of one daily cornstarch dose from baseline compared with placebo, the study’s secondary endpoint. They also had a numerical 3% mean increase in the percentage of glucose values in the hypoglycemic range, defined as less than 70 mg/dL, compared with placebo.
The reduction in daily cornstarch intake served as the surrogate endpoint supporting accelerated approval. The manufacturer is required to complete additional clinical trials to confirm the therapy's effectiveness.
Across two clinical studies, serious adverse reactions reported included anaphylaxis, adrenal insufficiency, elevated lactate levels, and hypoglycemia. Frequently reported adverse reactions included elevated transaminase levels, nausea, headache, constipation, and hyperglycemia. The rate of hypertriglyceridemia occurred in 29% of patients treated with pariglasgene brecaparvovec-opnr-treated patients vs 8% of those who received placebo.
The prescribing information includes warnings regarding anaphylaxis, liver toxicity, adrenal insufficiency, and tumorigenicity. Pariglasgene brecaparvovec-opnr should not be used during pregnancy.
Source: US Food and Drug Administration
