A one-time gene therapy for a rare metabolic disorder that requires patients to consume raw cornstarch every few hours to prevent life-threatening low blood sugar has received accelerated approval from the FDA.
The treatment, Genglycos (pariglasgene brecaparvovec-opnr), is now approved for adults and children eight years and older with glycogen storage disease type Ia, or GSDIa. The condition affects between 1,500 and 2,500 patients in the U.S. and an estimated 6,000 to 8,000 worldwide.
How the disease disrupts daily life
GSDIa results from a genetic deficiency in an enzyme that releases glucose from the liver into the bloodstream. Without this enzyme, patients face severe hypoglycemia, which can cause seizures, organ damage, or death. Current treatment depends on strict dietary control, primarily raw cornstarch, often in a slow-release form called Glycosade, to keep blood sugar stable.
“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.
A single infusion, a $2.7 million price tag
Genglycos uses an adeno-associated viral vector to deliver a working copy of the G6PC gene to liver cells. The therapy is given as a one-time infusion at designated treatment centers. Media reports indicate that the U.S. wholesale acquisition cost will be $2.7 million per patient, and financial assistance and patient support are available through www.ultracaresupport.com.
The FDA’s accelerated approval relied on data from the 48-week GlucoGene phase 3 study, which enrolled 46 participants aged eight and older. 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.
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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.
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).
Post-approval studies will track real-world outcomes
As part of the 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.
Genglycos is expected to be available within 30 days to 60 days.
Some patients facing similar challenges have been left without coverage due to work requirements, adding another layer of difficulty in accessing necessary treatments.
