By VETTAPHARMA reporter – Derek Roche: The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ultragenyx Pharmaceutical’s Genglycos (pariglasgene brecaparvovec-opnr), the first approved treatment for glycogen storage disease type Ia (GSDIa). The one-time gene therapy is approved to reduce daily cornstarch intake, as an adjunct to nutritional management, in adults and pediatric patients aged 8 years and older with the rare inherited metabolic disorder.
Genglycos is an AAV8-based gene therapy designed to deliver a functional G6PC gene to the liver, with the aim of restoring production of the deficient glucose-6-phosphatase enzyme. In GSDIa, deficiency of this enzyme prevents the body from properly releasing glucose from stored glycogen, resulting in potentially dangerous episodes of hypoglycemia, particularly during fasting. Current management relies heavily on frequent meals and strict, around-the-clock cornstarch supplementation.
The accelerated approval was supported by a randomized, double-blind, placebo-controlled clinical study in patients with GSDIa followed for 48 weeks after treatment. Genglycos produced a statistically significant 31% mean reduction from baseline in daily cornstarch intake compared with placebo, meeting the study’s primary endpoint. The therapy also produced a mean reduction of one cornstarch dose per day compared with placebo, meeting the secondary endpoint.
The FDA noted that reducing cornstarch intake was used as a surrogate endpoint reasonably likely to predict clinical benefit. As a condition of accelerated approval, Ultragenyx must conduct additional clinical studies to confirm the therapy’s effectiveness and long-term clinical benefit.
Safety findings across two clinical studies included serious adverse reactions such as anaphylaxis, adrenal insufficiency, elevated lactate levels, and hypoglycemia. Common adverse reactions included increased liver enzymes, nausea, headache, constipation, and hyperglycemia. Hypertriglyceridemia occurred in 29% of Genglycos-treated patients compared with 8% of placebo-treated patients. The prescribing information carries warnings for anaphylaxis, liver toxicity, adrenal insufficiency, and tumorigenicity, and Genglycos should not be used during pregnancy.
The approval represents a significant shift in the management of GSDIa by introducing a one-time gene therapy targeting the underlying genetic cause of the disease rather than relying solely on lifelong dietary management. Genglycos received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations, and the application also received a Rare Pediatric Disease Priority Review Voucher.
Quick FAQs
1. What Is Genglycos?
Genglycos (pariglasgene brecaparvovec-opnr) is a one-time AAV8-based gene therapy designed to deliver a functional G6PC gene to the liver and restore production of the glucose-6-phosphatase enzyme.
2. What Happened?
The FDA granted accelerated approval to Genglycos as the first approved treatment for glycogen storage disease type Ia, for adults and children aged 8 years and older to reduce daily cornstarch intake alongside nutritional management.
3. What Study Supported The Approval?
The approval was supported by a randomized, double-blind, placebo-controlled clinical study in patients with GSDIa followed for 48 weeks after treatment. The primary endpoint was the change in daily cornstarch intake.
4. What Is Glycogen Storage Disease Type Ia?
Glycogen storage disease type Ia is a rare inherited metabolic disorder caused by mutations affecting the G6PC gene, resulting in deficiency of glucose-6-phosphatase and an inability to maintain stable blood glucose levels during fasting.
5. What Were The Key Results?
Genglycos produced a 31% mean reduction in daily cornstarch intake compared with placebo, meeting the primary endpoint. It also reduced the number of daily cornstarch doses by a mean of one dose per day compared with placebo.
6. Why Is This Important?
Genglycos is the first approved treatment for glycogen storage disease type Ia and introduces a one-time gene therapy designed to address the underlying genetic cause of the disease, potentially reducing dependence on lifelong, intensive cornstarch supplementation.
