Ultragenyx Pharmaceutical has received accelerated approval from the U.S. Food and Drug Administration (FDA) for GENGLYCOS (pariglasgene brecaparvovec-opnr), also known as DTX401, for adults and children aged eight years and older with glycogen storage disease type Ia (GSDIa).
GENGLYCOS is a gene therapy designed to address the underlying cause of GSDIa, a rare genetic metabolic disorder that affects the liver’s ability to maintain normal blood glucose levels.
People with GSDIa have a deficiency in an enzyme needed to release glucose from the liver into the bloodstream. This can cause severe and potentially life-threatening episodes of low blood sugar, particularly during fasting or periods of metabolic stress.
Managing the condition typically requires patients to follow strict dietary schedules and take raw cornstarch regularly throughout the day and night. Even with careful management, missed doses or meals can put patients at risk of severe hypoglycemia, seizures and other serious complications.
GSDIa affects an estimated 1,500 to 2,500 people in the US and around 6,000 to 8,000 people worldwide across commercially accessible markets.
Ultragenyx said GENGLYCOS is designed to restore the body’s ability to break down glycogen and produce glucose when needed. In clinical studies, treatment reduced patients’ reliance on cornstarch, which the company said could help reduce the daily burden of managing the disease.
The FDA’s accelerated approval was supported by results from the Phase 3 GlucoGene study. The randomized, double-blind, placebo-controlled trial included 46 participants aged eight years and older who received either GENGLYCOS at a dose of 1.0 x 10¹³ GC/kg or placebo.
At Week 48, patients treated with GENGLYCOS showed a significant reduction in their cornstarch requirements compared with those receiving placebo. The difference was statistically significant, with a p-value of less than 0.001.
Participants were then able to switch to the alternative treatment and continued to be followed through later time points, including Weeks 96 and 144.
As part of the accelerated approval, Ultragenyx will conduct additional post-marketing monitoring. The company has agreed to provide two years of safety and efficacy data from 50 patients receiving commercial treatment and 20 control patients who cannot receive GENGLYCOS because they have anti-AAV8 antibodies.
The monitoring program will assess cornstarch requirements, fasting tolerance and other measures of treatment benefit. Participants from earlier clinical trials and new commercial patients will also be followed for up to 10 years.
Eric Crombez, chief medical officer at Ultragenyx, said the approval represents the company’s first gene therapy approval and an important milestone in its work to develop treatments for rare diseases.
The company will support eligible patients and caregivers through its UltraCare program, which includes specialized Gene Therapy Guides to help with insurance coverage, treatment support and the treatment process.
GENGLYCOS will be administered through a national network of Qualified Treatment Centers with specialized training in gene therapy. The treatment is manufactured at Ultragenyx’s Gene Therapy Manufacturing Facility in Bedford, Massachusetts.
The approval marks a significant development for the GSDIa community, where treatment has traditionally relied heavily on strict dietary management and around-the-clock monitoring. Ultragenyx said GENGLYCOS could provide patients with a new option aimed at addressing the underlying cause of the disease rather than only managing its symptoms.