FDA approves $2.7 million gene therapy for rare metabolic disorder

The FDA has granted accelerated approval for Genglycos (pariglasgene brecaparvovec-opnr) for adult and pediatric patients eight years and older with glycogen storage disease type Ia (GSDIa).

GSDIa is a rare genetic metabolic disorder caused by a deficiency of the enzyme needed to release glucose from the liver to the bloodstream. This deficiency can lead to life-threatening hypoglycemia and other serious complications. It affects between 1,500 and 2,500 patients in the United States and between 6,000 and 8,000 people worldwide.

Patients with GSDIa have been treated with dietary changes to maintain stable blood sugar. Cornstarch, particularly Glycosade, a long-acting cornstarch, has been used to manage patients with all types of glycogen storage diseases. But disease management with cornstarch can result in large swings in glucose.

“Day-to-day management of GSDIa requires a relentless regimen of raw cornstarch and strict dietary management that can be extraordinarily demanding for patients and families. Even with meticulous adherence to this regimen, patients must be perfect. Any missed cornstarch puts patients at risk of severe hypoglycemia, seizures, and even death,” said David Weinstein, M.D., MMSc, a leading expert in GSDIa, in a news release. He founded the Weinstein Rare Disease and Clinical Development Consulting and is now a consultant there.

Developed by Ultragenyx Pharmaceutical, Genglycos is an adeno-associated viral vector gene therapy designed to deliver a copy of the G6PC gene to liver cells to produce a normally functioning enzyme.

Genglycos is delivered as a one-time infusion through qualified treatment centers. Media reports indicate that the U.S. wholesale acquisition cost will be $2.7 million per patient, and Genglycos is expected to be available within 30 days to 60 days. Financial assistance and patient support are available through www.ultracaresupport.com.

The accelerated approval was based on data from the 48-week phase 3 GlucoGene study, which treated 46 participants aged eight years and older with Genglycos or placebo. In the modified intent-to-treat population, data from 44 patients provided the efficacy data. At week 48, eligible patients crossed over and received the alternate treatment.

Patients treated with Genglycos demonstrated a statistically significant mean reduction from baseline in daily cornstarch intake of 31% compared with placebo, the study’s primary endpoint. A mean reduction from baseline of one cornstarch dose per day was seen in the Genglycos group compared with the placebo, the study’s secondary endpoint.

Additionally, patients treated with Genglycos experienced clinically meaningful improvements in low levels of hypoglycemia (low blood sugar), improved levels of euglycemia (normal levels of blood sugar), and improved fasting tolerance. These clinical benefits translated to meaningful improvements in patient-reported quality of life, as measured by the Patient Global Impression of Change (PGIC) scale. The PGIC is a validated scale used to assess health or clinical status.

Genglycos was well tolerated. The most commonly reported adverse reactions included increased transaminases (elevation of liver enzymes), nausea, headache, constipation, and hyperglycemia. Genglycos-treated patients had a higher rate of hypertriglyceridemia (high blood triglyceride levels).

As part of accelerated approval, Ultragenyx has agreed to provide two years of safety and efficacy clinical data from open-label commercial treatment of 50 patients and 20 control patients through its existing GSDIa disease monitoring program. The control group will consist of patients who could not receive Genglycos because of the presence of anti-AAV8 antibodies.

This open-label study will provide more data to support the reduction in cornstarch clinical burden, fasting tolerance, and other measures in a post-marketing setting where patients can know their immediate glucose levels, and their cornstarch and diet can be managed more promptly by their physician.