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I – Gene & Cell Therapy Trials in Progress -> Gene & Cell Therapy Trials in Progress

4: Efficacy and Safety at Week 52 and up to Four Years in Adults with Glycogen Storage Disease Type IA (GSDIa): Results from a Phase 1/2 Clinical Trial and Long-Term Follow-Up Study of DTX401, an AAV8-Mediated, Liver-Directed Gene Therapy

Type: Clinical

Presentation Details
Session Title: Clinical Trials Spotlight Symposium
Location: Concourse Hall 152 & 153
Start Time: 5/18/2023 8:00
End Time: 5/18/2023 8:15

Background: Glycogen storage disease type Ia (GSDIa) results from a deficiency of glucose 6-phosphatase (G6Pase) which is essential for glycogenolysis and gluconeogenesis. DTX401 is an investigational adeno-associated virus serotype 8 (AAV8) vector expressing the human G6PC gene. Methods: An open-label, phase 1/2, dose escalation gene therapy trial (NCT03517085) evaluated the safety and efficacy of a single DTX401 intravenous infusion in 12 adults with GSDIa for 52 weeks. Three patients in Cohort 1 received DTX401 2.0 x 1012 genome copies (GC)/kg, and three patients each in Cohorts 2, 3, and 4 received 6.0 x 1012 GC/kg. Patients in Cohorts 1 through 3 received reactive steroids, and patients in Cohort 4 received a prophylactic steroid regimen to prevent transaminase elevation. All participants entered a long-term follow-up study (NCT03970278) to monitor safety and efficacy for up to 260 weeks after DTX401 administration. The data cutoff for this analysis was 06-Dec-2022. Efficacy Results: Mean (SD [range]) total daily cornstarch intake reduction from baseline to Week 52 was 70.0% (23.1 [28-100%]), p<0.0001 among 11 patients with a cornstarch assessment within the ±14 day analysis window for the Week 52 visit. From baseline to last available timepoint in the follow-up study (~4 years for three patients in Cohort 1), mean (SD [range]) total daily cornstarch intake reduction was 65.6% (24.3 [9-100%]), p<0.0001 for all 12 patients. Safety Results: All patients experienced a treatment-emergent adverse event (TEAE) and a related TEAE; however, no infusion-related or treatment-related serious adverse events (SAEs) were reported. There were three patients with five related TEAEs of hypertriglyceridemia and one patient with two related TEAEs of proteinuria. All SAEs were classified as serious due to hospitalizations and were determined to be unrelated to study drug by both the investigator and study sponsor; all resolved. Conclusions: DTX401 showed a positive efficacy and safety profile in all treated patients at Week 52 that was sustained for up to four years in patients enrolled in Cohort 1. Patients in all cohorts showed a significant reduction in cornstarch needs from baseline to both Week 52 and to the last available timepoint. All participants remain in the follow-up study and updated efficacy and safety results will be reported.

Rebecca Riba-Wolman1, David F. Rodriguez-Buritica2, Ayesha Ahmad3, Maria-Luz Couce Pico4, Terry G. Derks5, John Mitchell6, David A. Weinstein1, Deepali Mitragotri7, Andrew Alexander Grimm8, Eric Crombez7

1University of Connecticut, Farmington, CT,2University of Texas at Houston, Houston, TX,3University of Michigan, Ann Arbor, MI,4Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain,5University of Groningen, Groningen, Netherlands,6Montreal Children’s Hospital, Montreal, QC, Canada,7Ultragenyx Pharmaceutical Inc., Cambridge, MA,8Ultragenyx Pharmaceutical Inc., Novato, CA
 A.A. Grimm: None.

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