Trial Interviews to Explore Glycogen Storage Disease Type Ia Patient Experiences Following Gene Therapy

TL;DR

A gene therapy called DTX401 significantly reduced the burden of managing glycogen storage disease type Ia, improving patients' quality of life and reducing the need for frequent cornstarch intake.

Contribution

This study provides patient-reported outcomes from a gene therapy trial for GSDIa, highlighting its impact on quality of life and symptom burden.

Findings

Most participants reported symptom improvement and reduced disease burden following DTX401 treatment.

Participants showed high satisfaction with gene therapy at multiple timepoints, with minimal negative outcomes reported.

DTX401 led to reduced cornstarch intake and improvements in physical, emotional, and social functioning.

Abstract

Glycogen storage disease type Ia (GSDIa) is a rare, inherited, autosomal recessive deficiency of glucose-6-phosphatase (G6Pase), an enzyme necessary in glycogenolysis and gluconeogenesis. To maintain normal blood glucose levels and ensure survival, individuals living with GSDIa must frequently consume complex carbohydrates (eg, uncooked cornstarch). Dietary management can result in chronic complications and significant patient burden. DTX401 (pariglasgene brecaparvovec) is an investigational adeno-associated virus serotype 8 vector (AAV8)–based gene therapy designed to restore endogenous glucose production.

Patient experience interviews were conducted as part of an open-label, phase 1/2 dose-escalation trial (NCT03517085) evaluating the safety and efficacy of DTX401 in adults ≥18 years with GSDIa.

Telephone interviews were conducted at Weeks 24, 52, and 104, using a semistructured interview guide. Qualitative interview data were audio recorded, transcribed, coded, and analyzed.

Most (86%; n = 6/7) reported overall symptom improvement and reduced burden following DTX401 treatment. Three (43%) reported no negative outcomes following gene therapy; 4 (57%) mentioned at least one negative change attributed to instances of blood sugar instability, lifestyle, or diet adjustments. Satisfaction fluctuated across timepoints; however, most were somewhat satisfied/very satisfied with gene therapy at Weeks 24 (80%), 52 (86%), and 104 (86%). No participants reported being very dissatisfied.

Following DTX401 treatment, most participants reported substantial reduction in cornstarch intake and corresponding improvements in symptoms, physical function, diet management, emotional function, self-perception, social function, sleep quality, work performance, and overall health. Few negative changes were reported. While some results regarding met expectations were mixed, most indicated they would still want gene therapy even if they had to continue cornstarch and if they had continued diet restrictions, and most reported satisfaction with treatment. While the study had limitations, interview results suggest that DTX401 helps to address aspects of the condition and treatment that patients have identified as burdensome.

Most interviewees in this open-label trial of investigational DTX401 described positive experiences, including substantial reduction in burden and improved health-related quality of life following treatment throughout the trial. To optimize patient outcomes and experience with gene therapy, guidance on and close monitoring of dietary changes during implementation should be provided.

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