Ultragenyx to advance first gene therapy for glycogen storage disease post-phase 3 success

Ultragenyx is preparing to submit its gene therapy for glycogen storage disease (GSD) to regulatory bodies after promising results in a phase 3 clinical trial. The therapy, DTX401, demonstrated the ability to reduce patients' reliance on the current standard treatment, cornstarch.

GSD is a rare genetic disorder that affects the body's ability to store and break down glycogen, a type of sugar. Cornstarch is the only approved therapy for GSD. It is slowly digested, leading to a gradual release of glucose into the bloodstream, which helps manage the disease.

In the clinical trial, 49 patients with GSD Type 1a were given either DTX401 or a placebo over 48 weeks. Those who received the gene therapy saw a significant reduction in their need for daily cornstarch. On average, this group reduced their intake by 41.3%, compared to just 10.3% in the placebo group, achieving the primary goal of the study.

Remarkably, all participants treated with DTX401 experienced a reduction in cornstarch intake. Specifically, 68% saw their intake drop by 30% or more, and 37% reduced their intake by 50% or more. In contrast, only 13% and 4% of the placebo group achieved these reductions, respectively.

The study also measured secondary endpoints, including the reduction in daily cornstarch doses. The DTX401 group reduced their doses by an average of 1.1 per day, while the placebo group saw a minimal reduction of 0.2 doses. Additionally, the gene therapy showed meaningful improvements in the frequency and amount of nighttime cornstarch dosing.

Ultragenyx reported that DTX401’s safety profile was manageable and aligned with expectations. Some patients experienced hepatic effects, but these were non-serious and controlled using a prophylactic corticosteroid regimen.

Ultragenyx’s Chief Medical Officer, Eric Crombez, M.D., described the trial results as a significant milestone, noting that they were consistent with the outcomes from earlier phase 1/2 studies. Crombez emphasized that the improvements in treated patients highlight the therapy’s potential to enable the breakdown of glycogen in the liver, providing a new source of glucose for the body.

With these encouraging results, Ultragenyx plans to engage with regulatory authorities to discuss the next steps. The aim is to submit marketing applications by 2025.

Rebecca Riba-Wolman, M.D., Director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center and an investigator in the study, highlighted the daily challenges faced by GSD1a patients. She stressed the importance of a treatment that can alleviate these concerns without introducing significant risks.

“A disease like GSD1a requires constant vigilance to avoid severe low blood sugar and acidosis, particularly during the night,” Riba-Wolman noted. She underscored the necessity of a therapy that can improve the daily lives of GSD1a patients.

The promising results from Ultragenyx’s phase 3 trial bring hope for a new treatment option for GSD1a, potentially transforming the management of this lifelong condition.