Introduction: Myotonic dystrophy type 1 (DM1) is a rare, dominantly inherited progressive neuromuscular disorder. Delpacibart etedesiran (del-desiran; AOC 1001) is an investigational antibody–oligonucleotide conjugate designed to address the underlying genetic cause of DM1. The completed MARINA-OLE trial is a phase 2, open-label extension study that evaluated the long-term safety, tolerability, and efficacy of del-desiran. To gain insight into the lived experiences of those with DM1 and their caregivers, as well as to explore the perceived effects of del-desiran, a qualitative interview study was conducted with MARINA-OLE participants and their caregivers. These interviews provided their perspectives on DM1 and experiences in the trial in their own words.
Methods: This qualitative study involved semi-structured interviews with a group of MARINA-OLE participants (n=27) and a subset of caregivers (n=17) interviewed separately. The participants described themselves, how DM1 impacted their lives, what their lives were like before entering the trial, and their experiences during the trial. They were asked about their symptoms before and during the trial using a list of 31 symptoms within 6 domains (muscular, neurologic, gastrointestinal, cardiac/respiratory, emotional/psychological, metabolic/other). They were also asked about their general experiences with MARINA-OLE.
Results: The most frequently reported DM1-related concerns were myotonia, weakness, mobility, fatigue, sleepiness, balance, and pain. The impacts of DM1 on daily life notably differed among individuals. Of 27 MARINA-OLE participants, 22 reported improvements in ≥1 DM1-related symptoms. Improvements were noted in muscle, neurologic, gastrointestinal, and metabolic functions. Domains with the most respondents reporting no improvement were the psychological and social functions. Generally, interviews with caregivers followed a similar pattern to those in the MARINA-OLE participant interviews.
Conclusion: MARINA-OLE participants reported experiencing a range of DM1-related symptoms across multiple domains. The majority of interviewed participants reported improvements in ≥1 DM1-related symptoms. Improvement was noted with varying symptoms, a finding consistent with the known heterogeneity of presentation in individuals with DM1. Understanding their experiences with DM1 helps ensure the patient voice remains centered during drug development.