Positive AOC 1001 long-term data showing reversal of disease progression in people living with myotonic dystrophy type 1 across multiple endpoints; same key endpoints agreed for phase III HARBOR trial
Avidity Biosciences, Inc. a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs), announced new positive long-term AOC 1001 data from the MARINA open-label extension (MARINA-OLE ) trial showing reversal of disease progression in people living with myotonic dystrophy type 1 (DM1) across multiple endpoints including vHOT, muscle strength and activities of daily living when compared to END-DM1 natural history data
These endpoints are the same key endpoints that will be used in the global Phase III HARBOR trial for people living with DM1.
Avidity also announced delpacibart etedesiran as the approved international nonproprietary name of AOC 1001, abbreviated as del-desiran. Del-desiran (AOC 1001) is an investigational treatment designed to address the root cause of DM1, an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies.
"The long-term data from the MARINA-OLE study demonstrating that del-desiran improved measures of disease progression in DM1 patients compared to natural history data is remarkable," said John W. Day, MD, PhD, Professor of Neurology and Pediatrics, and Director, Division of Neuromuscular Medicine, Stanford University School of Medicine, an investigator of the MARINA and MARINA-OLE trials. "The favorable long-term safety data and consistent, durable improvement in myotonia, muscle strength and patient-reported outcomes measures show the potential of del-desiran to make a meaningful difference in the lives of DM1 patients. I am very encouraged by the prospect of del-desiran as a potential treatment for DM1."
Data Presented at 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 3-6: MARINA-OLE is an open-label, multi-center trial to evaluate the safety, tolerability, PK, PD, and efficacy of del-desiran (AOC 1001) in participants that were enrolled in the randomized, placebo-controlled, Phase 1/II MARINA clinical trial. Participants enrolled in the MARINA-OLE study receive quarterly doses of del-desiran (AOC 1001) regardless of whether they received active treatment or placebo in the MARINA study. All 37 participants that completed the MARINA trial remain on del-desiran (AOC 1001) in the MARINA-OLE trial.
Long-term efficacy data presented were assessed from 12 participants on 4 mg/kg del-desiran (AOC 1001) in the MARINA-OLE study. The endpoints used in the MARINA-OLE measure important aspects of the disease and correspond to those utilized in the ongoing END-DM1 natural history study. The long-term data from the MARINA-OLE trial are being presented in a poster session at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference being held March 3-6, 2024, in Orlando, Florida.
MARINA-OLE data compared to END-DM1 natural history data: For the first time new data were reported from END-DM1, a natural history study to establish biomarkers and clinical endpoints in DM1 by understanding the progression of myotonic dystrophy. Long-term del-desiran (AOC 1001) data from the MARINA-OLE study show reversal of disease progression in people living with DM1 across multiple endpoints including myotonia, muscle strength and patient reported activities of daily living compared to a matched END-DM1 natural history study population over one year.
Del-desiran long-term efficacy data from MARINA-OLE: In the MARINA-OLE study, del-desiran (AOC 1001) 4 mg/kg provided consistent and durable improvements in the following: i. Myotonia (video hand opening time, or vHOT) ii. Multiple measures of strength: a. Hand grip. b. Quantitative Muscle Testing (QMT) total score which includes hand grip; elbow extension and elbow flexion; knee extension and knee flexion, and ankle dorsiflexion iii. DM1-Activ, a patient reported outcome (PRO) that measures activities of daily living (e.g., taking a shower, visiting family or friends, and walking up stairs).
Del-desiran safety and tolerability data from MARINA-OLE: With over 265 infusions totaling 61.1 patient-years of exposure, del-desiran (AOC 1001) continues to demonstrate favorable safety and tolerability. In the MARINA-OLE study of del-desiran (AOC 1001): i All related adverse events (AE) were mild or moderate. ii. The most common related AEs reported in 2 or more participants in the MARINA-OLE were nausea and headache. iii. There were no study drug related SAEs iv. There have been no discontinuations in the MARINA-OLE study.
About the Phase II MARINA-OLE Study: MARINA-OLE is an open-label, multi-center trial designed to evaluate the long-term safety and tolerability of del-desiran (AOC 1001) in participants with DM1 who were previously enrolled in the MARINA Phase 1/II trial. This trial will continue to evaluate the safety, tolerability, PK, PD, and efficacy of del-desiran (AOC 1001) in participants enrolled in the randomized, placebo-controlled, Phase 1/II MARINA clinical trial. Participants enrolled in the MARINA-OLE study receive quarterly doses of del-desiran (AOC 1001) regardless of whether they received active treatment or placebo in the MARINA study. The total duration of active treatment with del-desiran (AOC 1001) in the MARINA-OLE study is approximately 24 months. Once patients have completed active treatment, there will be a nine-month safety follow-up period. Avidity may extend active treatment beyond 24 months at a future timepoint.
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