Ultragenyx Pharmaceutical has secured the US FDA's accelerated approval to GENGLYCOS (pariglasgene brecaparvovec-opnr), also known as DTX401, for adults and children aged 8 and older with glycogen storage disease type Ia (GSDIa).

 

The approval signifies the first therapy from Ultragenyx designed to directly target the underlying cause of the ultra-rare genetic disorder, which can cause life-threatening drops in blood glucose.

 

“The approval of GENGLYCOS fulfills our commitment to provide the first therapy that directly targets the root cause of GSDIa. The reduced reliance on cornstarch, experienced by patients in our clinical studies, demonstrates this gene therapy’s ability to establish the normal breakdown of glycogen to produce glucose during fasting or episodes of metabolic stress. 

 

"This ability to regulate glucose has alleviated the disease burden and has the potential to mitigate the risk of severe or life-threatening hypoglycemia for these patients,” said Eric Crombez, chief medical officer at Ultragenyx. 

 

“As our first gene therapy approval, GENGLYCOS represents an important achievement for our company and the realization of the promise of a powerful new tool to deliver transformative medicines for people living with rare diseases.”

 

GSDIa is caused by pathogenic variants in the G6PC gene, leaving patients deficient in an enzyme needed to release glucose from glycogen and other metabolic sources. The resulting inability to maintain normal blood glucose levels can lead to severe hypoglycemia, particularly during fasting and overnight.

 

For decades, management has relied heavily on raw cornstarch and strict dietary schedules to provide patients with an external source of glucose. The regimen can require round-the-clock monitoring and frequent dosing, while still leaving patients vulnerable to dangerous glucose fluctuations.

 

GSDIa affects an estimated 1,500 to 2,500 people in the U.S. and 6,000 to 8,000 worldwide in commercially accessible markets.

 

“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, one of the world's leading GSDIa experts. 

 

“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.”

 

“For families affected by GSDIa, every day revolves around strict schedules, overnight vigilance, and the constant worry that a missed meal or dose of cornstarch could trigger life-threatening hypoglycemia,” said David and Wendy Feldman, co-founders and current Board members at The Children’s Fund for Glycogen Storage Disease Research. 

 

“This approval is an incredibly meaningful milestone for a community that has spent decades hoping, advocating, and helping advance the research for new treatment options that could ease the burdens of this disease.”

 

The FDA's accelerated approval is based on results from the 48-week randomized, double-blind, placebo-controlled Phase 3 GlucoGene study, which enrolled 46 participants aged 8 and older.

 

Participants received DTX401 at a dose of 1.0 x 10^13 GC/kg or placebo. The trial showed a statistically significant reduction in cornstarch requirements among treated patients compared with placebo, with p<0.001.

 

Efficacy analyses at Week 48 included 44 participants in the modified intention-to-treat population: 20 treated with DTX401 and 24 who received placebo. Eligible participants then crossed over to the alternate treatment and continued to be followed, with additional analyses planned at Weeks 96 and 144.