Rare disease specialist Ultragenyx’s gene therapy Genglycos has received accelerated approval from the FDA for treatment of glycogen storage disease type Ia (GSDIa), a rare metabolic condition
This marks the fifth FDA approval for the California-based biotech, which has already developed two monoclonal antibodies, an enzyme replacement therapy, and an oral synthetic triglyceride for long-chain fatty-acid oxidation disorders, all of which are for treating rare diseases
GSDIa is ultra-rare in the United States and occurs in approximately 1 in 125,000 births. Estimates of the number of people currently living with the condition range from around 1,500 to 2,500, but the precise figure is uncertain because the total number of people with GSDIa is unknown
Genglycos is a one-time intravenous adeno associated viral vector (AAV) gene therapy for treatment of GSDIa in both children aged 8 years and above and adults. The therapy is designed to deliver a functional G6PC gene to liver cells. The goal is renewed production of glucose-6-phosphatase in the liver, enabling more normal glucose release from glycogen stores and reducing reliance on the current treatment of a strictly controlled diet and frequent uncooked-cornstarch doses
The approval was based on results from a 48-week Phase III trial with 44 participants that showed a statistically significant 31% mean reduction in daily cornstarch requirements versus placebo
The study demonstrated a meaningful reduction in treatment burden, but it did not establish improved long-term clinical outcomes such as fewer hypoglycemic events. Confirmatory studies will be required to verify long term clinical benefit. To fulfill this, Ultragenyx has agreed to provide safety and efficacy clinical data from open-label treatment of 50 patients and 20 control patients for two years
There were seven serious adverse reactions in the study, two anaphylaxis or infusion reactions, two adrenal-gland events, two cases of elevated lactate, and one hypoglycemia event. Like many AAV therapies Genglycos comes with a risk of elevated liver enzymes and some of the adverse events were linked to complications associated with the corticosteroids used to manage post-infusion liver inflammation
“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, MD, one of the world’s leading GSDIa experts, in a press statement
“The approval of Genglycos represents a major step forward for the GSDIa community and reflects almost 30 years of work and scientific progress aimed at improving safety and the quality of life of people living with this disease.”
No mention of treatment price was made in the company’s announcement, but it does say the company will help enable access for eligible patients by providing “support to help enrolled patients and caregivers navigate access to treatment through its UltraCare program.”
News & FeaturesAdeno associated viral vectorAdverse drug reactionsDiet therapyGene therapy (Therapeutics)GenesMetabolic disordersRare diseasesUltragenyxGenglycos
