Qualitative Study of the Patient Experience with Venglustat for Gaucher Disease Type 3 in a Phase 2 Open-Label, Multicenter, Multinational Study (LEAP).

Introduction Gaucher disease type 3 (GD3) is a genetic, progressive lysosomal storage disorder characterized by visceral manifestations and chronic neurologic symptoms (e.g., horizontal ophthalmoplegia/supranuclear gaze palsy, ataxia, dystonia). The investigational agent venglustat is being studied in combination with imiglucerase as potential treatment for systemic and neuronopathic manifestations of GD3 in a single-arm, open-label, phase 2 trial (LEAP; N = 11). To understand perceived changes in GD3 symptoms from the perspectives of patients, caregivers, and clinicians, we conducted a qualitative case study of selected LEAP participants.Methods Four patients in LEAP (age range, 20-28 years), four of their caregivers, and three clinicians involved in LEAP were interviewed individually by moderators using semi-structured guides. Clinicians' perceptions were based on observation of interviewed patients and those in LEAP who were not interviewed, as well as information provided by other staff involved in LEAP, patients, and caregivers.Results Reported changes in GD3 symptoms varied among patients and among reporters. Only eye movement was spontaneously mentioned as improved by at least one patient, caregiver, and clinical expert. Symptom improvement also varied in terms of time to improvement. Within the first weeks, improvements were seen in understanding new information or complex instructions, remembering the weekday, eye movement, tremor, and seizures. Changes in alertness, engagement and responsiveness, memory, and concentration appeared after months or a year. Most caregivers and all clinical experts reported greater patient independence (e.g., increased ability to perform activities of daily living or travel independently during the trial) as a perceived treatment effect on a GD3 impact. For one patient who perceived benefits from venglustat therapy, pharmacokinetic analyses during LEAP found low to undetectable venglustat levels in their plasma and cerebrospinal fluid.Conclusion Outcomes from this study provide insights into GD3 symptoms and the early signaling of changes reported during venglustat therapy.Trial Registration ClinicalTrials.gov identifier, NCT02843035.