Drug Update · Rare Disease

DTX401 Achieved 68% Cornstarch Reduction in Adults With GSDIa

July 13, 2026

mean cornstarch reduction

68% (20%) reduction to 85 g at Week 52 from 284 g baseline; p < 0.001 [1]

time to hypoglycemia

Increase from 5.0 (1.6) to 6.9 (2.7) minutes/gram, mean (SD) increase 46% (72%) at Week 52 [1]

participants

12 adults with GSDIa enrolled; 10 participants had paired cornstarch values at baseline and Week 52 [1]

dosing (trial)

Cohort 1: 2.0 × 10^12 GC/kg (n=3); Cohorts 2–4: 6.0 × 10^12 GC/kg (n=3 each) [1]

safety summary

All participants experienced a TEAE and a related TEAE; no dose‑limiting toxicity, no TEAE leading to discontinuation, no TEAE leading to death, and no serious treatment‑related TEAE through Week 52 [1]

Clinical Perspective

Clinicians treating adults with glycogen storage disease type Ia (GSDIa) and adult patients with GSDIa should be aware of investigational liver‑directed AAV8 gene therapy outcomes reported to Week 52. The source‑confirmed data support that a single infusion of DTX401 was associated with substantial reductions in daily cornstarch requirement and an increase in time to hypoglycemia at Week 52, alongside no dose‑limiting toxicities or treatment‑related deaths in this small cohort. How durable are the metabolic benefits beyond 52 weeks and how these outcomes compare with other investigational or approved approaches in broader populations remain open questions?

Editorial Team · Rare Disease

DTX401, an AAV8‑mediated liver-directed gene therapy, produced a mean total daily cornstarch intake reduction of 68% (20%) at Week 52 in adults with glycogen storage disease type Ia (GSDIa) in an open‑label phase 1/2 trial (NCT03517085) ^[1]. The single‑infusion trial reported no dose‑limiting toxicities and no study discontinuations or deaths related to treatment through Week 52 ^[1].

Clinical Context

DTX401 is an investigational adeno‑associated virus serotype 8 (AAV8) vector expressing the human G6PC1 gene that encodes glucose‑6‑phosphatase, the enzyme deficient in GSDIa, and is intended as a liver‑directed gene therapy for GSDIa ^[1]. GSDIa is caused by G6Pase deficiency and management commonly includes a medically prescribed diet that typically includes daily uncooked cornstarch doses to maintain euglycemia, including overnight cornstarch administration as reported in the trial background ^[1]. The trial was conducted by academic metabolic disease centers with involvement from Ultragenyx Pharmaceutical Inc., which provided the investigational agent and support for the study ^[1]. The FDA defines gene therapy as an approach that modifies expression of a gene or alters biological properties of living cells for therapeutic use, which encompasses viral vector products such as AAV8 used in DTX401 ^[2].

Key Findings

DTX401 achieved a mean (SD) total daily cornstarch intake reduction of 68% (20%), from 284 g at baseline to 85 g at Week 52 in the 10 participants with available values at both time points (p < 0.001) in the phase 1/2 trial NCT03517085 ^[1].
Mean (SD) time to hypoglycemia in minutes/gram of carbohydrate during a controlled fasting challenge increased from 5.0 (1.6) at baseline to 6.9 (2.7) at Week 52, a mean (SD) increase of 46% (72%) ^[1].
DTX401 showed a favorable safety and efficacy profile at Week 52, with all participants experiencing at least one treatment‑emergent adverse event (TEAE) and a related TEAE, but with no dose‑limiting toxicity, no TEAE leading to study discontinuation, no TEAE leading to death, and no serious treatment‑related TEAE reported through Week 52 ^[1].

Safety & Tolerability

All participants experienced a treatment‑emergent adverse event (TEAE) and a related TEAE during the trial ^[1].
No participant experienced a dose‑limiting toxicity, a TEAE leading to study discontinuation, a TEAE leading to death, or a serious treatment‑related TEAE through Week 52 ^[1].
Corticosteroids were administered to mitigate vector‑induced inflammatory response in the study protocol ^[1].

Study Design

This was an open‑label, phase 1/2, dose‑escalation, 52‑week gene therapy trial that evaluated a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085) ^[1]. Three participants in Cohort 1 received DTX401 2.0 × 10^12 genome copies (GC)/kg, and three participants each in Cohorts 2, 3, and 4 received 6.0 × 10^12 GC/kg; corticosteroids were administered to mitigate vector‑induced inflammatory response ^[1]. Details on the prespecified primary endpoint wording, longer‑term follow‑up beyond Week 52, and full statistical analysis plan were not available in the provided source excerpts ^[1]. Clinicians should consult current prescribing information for complete dosing guidance.

FAQ

Q1 What did the NCT03517085 trial show?

The open‑label phase 1/2 trial of DTX401 in 12 adults with GSDIa reported a mean (SD) reduction in total daily cornstarch intake of 68% (20%), from 284 g at baseline to 85 g at Week 52 in 10 participants with available paired values (p < 0.001). The trial also showed a mean (SD) increase in time to hypoglycemia during a controlled fasting challenge from 5.0 (1.6) minutes/gram at baseline to 6.9 (2.7) minutes/gram at Week 52, a mean (SD) increase of 46% (72%). The study authors described a favorable safety and efficacy profile at Week 52.

Q2 Who was enrolled in the trial?

The trial enrolled 12 adults with glycogen storage disease type Ia (GSDIa) and evaluated a single DTX401 infusion with 52‑week follow‑up; three participants in Cohort 1 received 2.0 × 10^12 GC/kg and three participants each in Cohorts 2–4 received 6.0 × 10^12 GC/kg. Corticosteroids were administered per protocol to mitigate vector‑induced inflammatory response. The ClinicalTrials.gov Identifier for the study is NCT03517085.

Q3 What were the side effects in the trial?

All participants experienced at least one treatment‑emergent adverse event (TEAE) and a related TEAE. No participant experienced a dose‑limiting toxicity, no TEAE led to study discontinuation, no TEAE led to death, and no serious treatment‑related TEAE was reported through Week 52. Corticosteroids were used during the study to address potential vector‑induced inflammation. Specific named adverse events beyond the TEAE classification were not detailed in the provided source excerpts.

Q4 What does the trial mean for clinical practice?

The Week 52 data indicate that a single infusion of DTX401 may reduce reliance on daily cornstarch therapy and may prolong time to hypoglycemia in adults with GSDIa in this small cohort, while showing no dose‑limiting toxicities or treatment‑related deaths through one year. These findings may inform discussions between metabolic disease clinicians and patients about emerging investigational gene therapy approaches, but broader and longer‑term data are needed to define durability, generalizability, and comparative safety. Clinicians should consult ongoing trial reports and future regulatory guidance for updates on patient selection and clinical use.

DTX401 Achieved 68% Cornstarch Reduction in Adults With GSDIa

DTX401 Achieved 68% Cornstarch Reduction in Adults With GSDIa

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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