INTRODUCTION: No FDA-approved therapy currently exists for glycogen storage disease type 1a (GSD1a). Beam Therapeutics is developing BEAM-301 to treat individuals with GSD1a who are homozygous or compound heterozygous for the G6PC-pArg83Cys (p.R83C) variant. BEAM-301 is an in-vivo, liver-targeting lipid nanoparticle formulated investigational therapy designed to correct the p.R83C variant, the most common variant responsible for causing GSD1a. To create a patient-reported outcome (PRO) measure for the BEAM-301 Phase 1/2 clinical trial, we conducted a qualitative interview study to identify key signs , symptoms and impacts of GSD1a in individuals aged ≥12 years with the p.R83C variant(s); participant feedback was used to inform the development of a new measure to assess GSD1a-associated burden of illness in adults and adolescents.
METHODS: A targeted literature review, expert clinician, and caregiver feedback informed the preliminary identification of concepts for a disease-specific PRO measure. Following RTI IRB approval of this research, were recruited via advocacy groups and clinician referral. Qualitative interviews were conducted with 16 participants (10 female, 6 male) via Zoom or telephone across 3 rounds with individuals with self-reported p.R83C variant GSD1a and currently experiencing symptoms. The age range included 4 adolescents (aged 12-17 years) and 12 adults (aged ≥ 18 years). These hybrid concept elicitation and cognitive debriefing interviews aimed to identify and refine concepts and items related to GSD1a disease burden.
RESULTS: The 16 participants described a diverse range of GSD1a-related symptoms and impacts. The current standard of care (e.g., glucose/cornstarch supplementation every 3-4 hours) was described as posing a substantial burden. Participants most frequently reported symptoms of fatigue, sweatiness, and hunger. Fatigue, anxiety, and hypoglycemia were reported as the most bothersome symptoms. Participants’ experiences with GSD1a symptoms ranged from mild to very severe, including feelings of irritability to serious health consequences. Participants emphasized the importance of addressing glucose instability to prevent life-threatening GSD1a impacts. Hypoglycemia was identified as the most crucial symptom to treat, with a unanimous preference for longer-duration treatment effect compared to the current standard of care.
CONCLUSION: Due to the heterogeneous nature of the disease, we identified unique symptom concepts through the interviews. This diversity observed across participant experiences aligns with findings in the literature, even amongst individuals with the same GSD1a genetic variant and highlights the importance of the development of GSD1a-specific PRO measures to capture the participant experience with treatment in a clinical trial setting. The newly developed PRO measure will be utilized to derive a clinical endpoint in the BEAM-301 clinical trial.
