Ultragenyx's gene therapy shows significant improvements in daily life for GSDIa patients

Ultragenyx Pharmaceutical Inc. has announced significant findings from a 96-week trial of its gene therapy, GENGLYCOS™ (DTX401), for treating glycogen storage disease type Ia (GSDIa). The study, published in The Journal of Inherited Metabolic Disease, demonstrated substantial improvements in daily life for patients with GSDIa, offering hope for better management of the disease.

At the conclusion of the 96-week trial, participants across treatment and crossover groups experienced a 61% reduction in daily cornstarch intake while maintaining glycemic control. This reduction was particularly notable, with 83% of DTX401-treated participants achieving or exceeding their expectations for meaningful cornstarch reduction by Week 48. By Week 96, 33% of the DTX401 treatment group and 42% of the crossover group completely eliminated nighttime cornstarch dosing, significantly reducing sleep disruption.

Dr. John Mitchell, lead author of the publication and a pediatric endocrinologist, highlighted the significance of these findings: "The reduction in overnight cornstarch dosing will have the most meaningful impact by reducing sleep disruption. The patient-reported outcomes included in the publication underscore the profound impact that cornstarch reductions may have on daily life. Long-term outcomes from the 96-week period showing continued improvements are particularly important, offering valuable insight into how post-treatment management may continue to evolve."

Eric Crombez, M.D., chief medical officer at Ultragenyx, further emphasized the potential of this gene therapy: "These results demonstrate the potential of gene therapy to provide greater stability in day-to-day life for patients with GSDIa and may help guard against the risk of severe hypoglycemia associated with missed doses of raw cornstarch. Most patients achieved cornstarch reductions that met or exceeded their own expectations, with substantially less overnight treatment burden and reduced dependence on the around-the-clock cornstarch need that defines life with this disease."

The study also showed that participants maintained low levels of hypoglycemia and improved levels in the euglycemic range (70-120 mg/dL) throughout the second year of the trial, despite substantial reductions in daily cornstarch intake. Participants treated with DTX401 also experienced improved normalized fasting tolerance in a controlled fasting challenge, supporting the potential for protection from severe hypoglycemia.

Patient-reported outcomes indicated that 83% of DTX401-treated participants met or exceeded their baseline expectations for meaningful cornstarch reduction at Week 48, with continued improvements through Week 96. At Week 48, 79% of DTX401-treated participants reported improvement in GSDIa on the Patient Global Impression of Change, compared with 52% of placebo-treated participants.

The publication provides additional insights into the nighttime cornstarch burden, a significant aspect of managing GSDIa. Among participants who initially required nighttime cornstarch at baseline, 50% of DTX401-treated participants eliminated at least one nighttime cornstarch dose by Week 48, compared with 7% of placebo-treated participants. By Week 96, 67% of participants in both treatment groups had reduced their nighttime cornstarch dosing.

DTX401 was generally well-tolerated, with an acceptable safety profile. The most common treatment-related adverse events were transient elevations in liver enzymes, which were generally non-serious and managed with prophylactic corticosteroids. The study did not observe AAV8 class effects of dorsal root ganglion toxicity, malignancy, or thrombotic microangiopathy.

Importantly, the treatment did not induce severe hypoglycemic episodes, and participants were able to transition to a more balanced, food-based diet closer to the U.S. Dietary Guidelines for the general population.

GENGLYCOS (pariglasgene brecaparvovec-opnr) is indicated to reduce daily cornstarch intake as an adjunct to nutritional management in adult and pediatric patients 8 years of age and older with glycogen storage disease type Ia (GSDIa). The indication is approved under accelerated approval based on reduction in daily cornstarch intake, and continued approval may be contingent upon verification of clinical benefit in confirmatory trials.

Safety information for GENGLYCOS includes warnings and precautions related to hypersensitivity reactions, hepatotoxicity, and adrenal insufficiency. Patients should be monitored for signs and symptoms and treated as necessary.