dm+d

Unassigned

New Medicines

Glycogen storage disease type I

Information

New molecular entity
Ultragenyx
Ultragenyx

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes
Jan 22DTX401 has orphan drug designation in the US and EU, and Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designation in the US [1].

Category

An adeno-assoicated virus serotype 8 vectored gene therapy designed to deliver stable expression and activity of glucose-6-phosphatase-α using a single intravenous infusion.
Glycogen storage disorder type I is inherited as an autosomal recessive disorder. Prevalence is unknown. Annual incidence is about 1/100,000 births. Glycogen storage disorder type Ia is the more frequent type, representing about 80% of glycogen storage disorder type I pts. [2]
Glycogen storage disease type I
Intravenous infusion

Trial or other data

Nov 21Company initiates PIII study to evaluate the safety and efficacy of DTX401 in pts 8 years and older with glycogen storage disease type Ia (EudraCT2020-004184-12; NCT05139316). The randomised, double blind placebo controlled study intends to enrol approximately 50 pts in the US, Netherlands, Spain, Denmark and might expand to other countries. Pts will be randomised 1:1 to DTX401 or placebo group, and followed closely for 48 weeks. At week 48 eligible pts will cross over and receive DTX401 if they had previously received placebo or placebo if they had previously received DTX401, and will be followed closely for an additional 48 weeks. Primary outcome measure includes % change from baseline to week 48 in daily cornstarch intake and change from baseline to week 48 in % time spent in normal glucose control (60 to 120 mg/dL [3.3 to 6.7 mmol/L]). Estimated completion date is Apr 24. [3]
Jan 21Company reports positive results for NCT03517085 (n=9). At the primary evaluation timepoint at Week 52, the overall mean reduction in cornstarch was 77% across all three cohorts, including two pts in Cohort 3 showing a reduction of greater than 75%. All pts continue to demonstrate improved glucose control while tapering or discontinuing oral glucose replacement with cornstarch and improvements in energy metabolism pathways over the long term. DTX401 was shown to be well tolerated. Pts reported improvements in both their physical and mental health. [4]
Jul 19A prospective cohort study was initiated to follow up pts administered DTX401 for glycogen storage disease type I in NCT03517085 (n= 12, NCT03970278). The aim of the study is to determine long term safety of DTX401 given as a single intravenous infusion. Primary outcomes included adverse events and serious adverse events up to 260 weeks after administration. Estimated completion date is Dec 25. [3]
May 18A PI/II open-label parallel assignment study investigated safety of single doses of DTX401 in adults with glycogen storage disease type Ia was initiated (n=12, NCT03517085). Pts were monitored for 52 weeks following administration. Pts were allocated into 4 cohorts of different doses. Primary outcomes included adverse events and serious adverse events up to 52 weeks. Study locations include US, Canada, Netherlands and Spain. Estimated completion date is Nov 21. The lowest dose is reported as 6.0 × 10^12 GC/kg given as a single intravenous infusion. [3]