Ultragenyx Pharmaceutical Inc. announced positive longer-term efficacy and safety data from Phase 1/2 studies of DTX401 for the potential treatment of Glycogen Storage Disease Type Ia (GSDIa) and DTX301 for the potential treatment of Ornithine Transcarbamylase (OTC) deficiency. Results demonstrate ongoing durability of response and safety for both gene therapy programs as of the data cutoff date. Data were presented this week at the American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting.

DTX401 (GSDIa) Phase 1/2 Update: All 12 patients in the study continue to demonstrate improved glucose control, experiencing reductions in oral glucose replacement with cornstarch. Overall, patients reached a mean total daily reduction of cornstarch intake of 70% (p-value<0.0001) from baseline to the last available timepoint. Three patients in the first cohort have sustained responses for up to 3.5 years since treatment.

Continuous glucose monitoring was introduced in the third cohort, and data indicate that these patients achieved significant reductions in average cornstarch intake while increasing the time spent in euglycemia, defined by blood glucose levels in the normal range of 60 mg/dL to 120 mg/dL. Specifically, average cornstarch intake was reduced by 65% at Weeks 49 to 52 compared with Weeks 1 to 4, while euglycemia increased by 14% in the same period. All three patients in the fourth cohort have completed a tapering prophylactic steroid regimen and have demonstrated reductions in daily cornstarch intake, while the average percentage of time in euglycemia for these patients remained stable.

When patients were interviewed at 52 weeks, they reported more energy and stamina, better mental clarity, improved glycemic control independent from cornstarch, improved sleep quality and improvements in health-related quality of life related to cornstarch intake reduction. Patient Global Impression of Change (PGIC) scores at the Week 52 visit indicated that 67% of patients (n=9) felt their GSDIa was moderately or much improved since the start of the study. Across the Phase 1/2 study, there have been no infusion-related adverse events and no treatment-related serious adverse events (SAEs) reported.

DTX301 (OTC) Phase 1/2 Update: Four out of the five patients treated at the highest dose (1.7 x 10^13 GC/kg dose) – the dose specified for the Phase 3 study – have responded and remain clinically and metabolically stable. Overall, the seven responders of the 11 total patients treated across all cohorts remain clinically and metabolically stable. Six patients enrolled in the first three cohorts demonstrated durable response with 2 to 4.5 years of follow-up after treatment.

One patient enrolled in the last cohort also achieved complete response prior to the 1-year follow-up. Four complete responders have discontinued ammonia-scavenger medications and liberalized their diet within one year. In the prophylactic steroid cohort, one of two patients demonstrated a complete response.

The second patient was a responder at week 36, but viral infections and an inability to sustain increased protein intake in the presence of lowered medication led to catabolism. The patient was considered a nonresponder as of the 52-week visit. Once the patient is metabolically stable, iwill reinitiate tapering of baseline disease management.

Across all cohorts of the Phase 1/2 study, no treatment-related serious adverse events, infusion-associated reactions or dose-limiting toxicities have been reported. All reported adverse events have been Grade 1 or 2 during the main study except for one patient with Grade 3 hyperammonemic crises assessed as unrelated to DTX301. All patients have enrolled in the six-year extension study.

No patient who received corticosteroids experienced an AE of increased ammonia, hyperammonemia, or hyperammonemic crisis (HAC) that was associated with corticosteroid administration.