Initial Results of the Phase 2 Open-Label Extension Study of AOC 1001 in Adults with Myotonic Dystrophy Type 1: MARINA-OLE


Clinical Trials

Poster Number: T307


Nicholas Johnson, MD, Virginia Commonwealth University, John Day, MD, PhD, Stanford University Medical Center, Johanna Hamel, MD, University of Rochester, Charles Thornton, MD, University of Rochester, S H Subramony, M.D., Univsersity of Florida, Fixel Center for Neurological Disorders, Payam Soltanzadeh, MD, UCLA, Jeffrey Statland, MD, University of Kansas Medical Center, Miriam Freimer, MD, Ohio State University, Dianna Quan, University of Colorado, Ben Knisely, Avidity Biosciences, Inc., Antonia Davidson, MD, FACP, Avidity Biosciences, Brad McEvoy, DrPH, Avidity Biosciences, Inc., li tai, MD.PhD., Avidity, Elizabeth J Ackermann, PhD, Avidity Biosciences, Inc.

Objective: The primary objective of the MARINA-OLE study is to evaluate the long-term safety and tolerability of AOC 1001 in adults with myotonic dystrophy type 1 (DM1).

Background: DM1 is a rare, dominantly inherited, progressive neuromuscular disease caused by a toxic gain-of-function mutation in the DM1 protein kinase (DMPK) gene. Currently, no disease-modifying therapies exist.

AOC 1001 is an antibody oligonucleotide conjugate (AOC), comprised of a DMPK siRNA conjugated to a humanized antibody targeting human transferrin receptor 1 (TfR1), designed for functional delivery to muscle cells, including the heart, to reduce the toxic DMPK mRNA.

Design: MARINA-OLE (NCT05479981) is a phase 2 open-label extension of the MARINA (NCT05027269) study to evaluate the safety, tolerability, and efficacy of AOC 1001 administered intravenously to adult DM1 patients. Patients who completed the 6-month MARINA trial were eligible to enroll in MARINA-OLE. AOC 1001 is administered intravenously at quarterly intervals. The active treatment period is 24 months.

Results: The MARINA-OLE study is currently ongoing. All eligible participants have enrolled and continue to receive AOC 1001 (N=37). Data from MARINA-OLE will provide the first long-term results of any AOC and DMPK-targeted therapy in clinical development. The first assessment of these data will include long-term safety and tolerability and exploratory efficacy assessments that include measures of myotonia, hand function, strength, and mobility. These initial results will be presented.

Conclusion: Long-term safety and efficacy data of AOC 1001 continue to support the findings in MARINA. AOC 1001 represents a novel potential therapy addressing the underlying cause of DM1.