Ultragenyx targets 2025 filings for glycogen storage disease gene therapy

Ultragenyx Pharmaceutical is gearing up to seek regulatory approval for its experimental gene therapy, DTX401, in 2025. This decision follows promising results from a Phase III clinical trial focused on glycogen storage disease type 1a (GSDIa). GSDIa is a rare genetic disorder that impairs the body's ability to control blood sugar levels due to a faulty gene responsible for producing the G6Pase-α enzyme. At present, approximately 6,000 individuals worldwide are affected by GSDIa, and they manage their condition predominantly through stringent dietary regimens involving cornstarch. This method has been the cornerstone of GSDIa treatment for over three decades.

The 48-week Phase III trial, named GlucoGene, involved 44 participants aged eight and above. The study's primary goal was to evaluate the effectiveness of DTX401 compared to a placebo. Participants were randomly divided into two groups, with one group receiving DTX401 at a dose of 1.0 x 10^13 GC/kg and the other receiving a placebo. The primary endpoint was the reduction in daily cornstarch intake, a critical measure for evaluating the therapy's effectiveness.

Results showed that DTX401 achieved a significant 41.3% reduction in daily cornstarch intake, compared to just 10.3% in the placebo group. All participants treated with DTX401 experienced some level of reduction in their cornstarch intake. Specifically, 68% of these patients saw their cornstarch intake decrease by 30% or more, and 37% of them experienced a reduction of at least 50%. In stark contrast, only 13% and 4% of patients in the placebo group met these thresholds, respectively.

In addition to the primary endpoint, the study also assessed secondary outcomes, such as the reduction in the number of daily cornstarch doses. Patients treated with DTX401 reported an average reduction of 1.1 doses per day, compared to a 0.2 dose reduction in the placebo group. Another significant finding was the improvement in the frequency and quantity of nighttime cornstarch dosing for those treated with DTX401.

Safety is always a primary concern in clinical trials, and DTX401 displayed an "acceptable and expected" safety profile. The observed side effects were consistent with those seen in earlier Phase I/II trials. Importantly, any vector-induced effects on the liver were non-serious and manageable with a prophylactic corticosteroid regimen. The study reported no AAV8 class effects, such as dorsal root ganglion toxicity or thrombotic microangiopathy, which are potential concerns in gene therapy trials.

In summary, Ultragenyx Pharmaceutical's investigational gene therapy, DTX401, has shown encouraging results in reducing cornstarch intake among GSDIa patients, potentially offering the first disease-modifying treatment for this rare genetic disorder. With its promising efficacy and safety profile, DTX401 could transform the management of GSDIa, providing a significant improvement over the current standard of care. The company plans to file for regulatory approval in 2025, marking a significant step forward for patients suffering from this debilitating condition.