The US Food and Drug Administration (FDA) has granted accelerated approval for Genglycos (pariglasgene brecaparvovec-opnr), also known as DTX401, in patients eight years and older with glycogen storage disease type 1a (GSD1a).
GSD1a is a rare metabolic disorder that impairs glucose production through glycogenolysis and gluconeogenesis. It is caused by mutations in the G6PC gene, affecting glucose-6-phosphatase (G6Pase) activity. Without functional G6Pase-α, patients cannot sustain fasting glucose and if not managed, can lead to serious kidney and liver concerns. The dietary standard of care, uncooked cornstarch every three to six hours, nocturnal feeds, and strict exclusion of fructose, galactose, and sucrose, has sustained life but cannot correct the underlying enzymatic deficiency.
DTX401 is an adeno-associated virus serotype 8 (AAV8) vector expressing the human G6PC1 gene that encodes G6Pase. The approval is based on data from the 48-week randomized, double-blind, placebo-controlled phase 3 GlucoGene (NCT05139316) study which treated participants aged eight years and older with DTX401 or placebo.
A total of 44 participants in the modified intention-to-treat population provided efficacy data at week 48, following treatment with DTX401 or placebo. Within the trial, treatment with DTX401 showed a 31% reduction in the cornstarch requirements in the treated group, compared to placebo. At week 48, eligible participants crossed over and received the alternate treatment. After crossover, participants continued to be followed, with analyses conducted at week 96 and week 144.
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 enhancement of its existing GSDIa Disease Monitoring Program (DMP). The control group will consist of patients who sought commercial treatment but cannot be treated with DTX401 due to the presence of anti-AAV8 antibodies. The 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. The DMP will also evaluate previously treated clinical trial participants as well as these new commercial patients for a total of 10 years.
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To learn more about GSD1a and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/