Delpacibart etedesiran

An investigational infusion for myotonic dystrophy type 1 (DM1) developed by Avidity Biosciences and now owned by Novartis, given into a vein every 8 weeks. On September 8, 2026 Novartis reported that the 159-person Phase 3 HARBOR trial did not show a statistically significant improvement over placebo on its primary endpoint, video hand opening time, a measure of hand myotonia, while noting evidence of activity on secondary endpoints. Novartis is reviewing the full data set and talking with regulators about whether and how to continue^[1]. The drug holds Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA^[1]. Its Phase 1/2 MARINA study, published in the New England Journal of Medicine in February 2026, had shown a mean 40% reduction in the toxic DMPK RNA in muscle^[2].

DM1 is caused by a stretch of DNA in the DMPK gene that repeats far too many times, usually 50 to several thousand copies instead of 5 to 37. The RNA copied from it forms hairpin clumps inside the cell nucleus that trap a protein called MBNL, which the cell needs to assemble many other proteins correctly, so muscle, heart and nerve cells end up building faulty versions of them. Del-desiran is a small interfering RNA, a short double strand of synthetic genetic code that directs the cell's own machinery to chop up the DMPK RNA, attached to a whole antibody that grips transferrin receptor 1 on muscle cells so the cell takes the drug in^[5][1].

In the 38-person MARINA study, 2 people had severe serious adverse events, one of them judged drug-related, and 1 person in the 4 mg/kg group left the study^[2]. The FDA put a partial clinical hold on new enrollment in September 2022 after that serious adverse event, then eased it in May 2023, allowing more people onto the 4 mg/kg dose and new enrollment at 2 mg/kg^[3][4]. Novartis said HARBOR's safety findings were generally consistent with earlier data but has not yet published the detailed rates^[1].

Given by infusion into a vein every 8 weeks in the HARBOR trial; the MARINA study tested single doses of 1 mg/kg and repeated doses of 2 and 4 mg/kg, measured as the siRNA component^[2][5].

Delpacibart etedesiran is currently in trial failed clinical trials for Myotonic Dystrophy. It has not yet received FDA approval.

HARBOR did not meet its primary endpoint. On September 8, 2026 Novartis said the trial did not show a statistically significant improvement over placebo in video hand opening time, the measure of hand myotonia it was built around, though some secondary and exploratory measures showed activity. Novartis has not said whether it will file, run another study or stop.

As of October 2026 Novartis says it is evaluating the full HARBOR data set and will talk with regulators about the most appropriate path. The HARBOR open-label extension is continuing for people who completed the main study. Patient groups led by the Myotonic Dystrophy Foundation have publicly asked Novartis to keep the program going.

Both carry an RNA drug into muscle on an antibody aimed at transferrin receptor 1 and both target the toxic DMPK RNA. Del-desiran is a small interfering RNA on a whole antibody; DYNE-101 (zeleciment basivarsen) is an antisense oligonucleotide on an antibody fragment. Del-desiran missed its Phase 3 primary endpoint; DYNE-101's registrational results are due in the first quarter of 2027.

A single participant in the 4 mg/kg group of the MARINA study had a serious adverse event, and the FDA paused enrollment of new participants in September 2022 while people already in the study kept their doses. In May 2023 the FDA eased the hold, allowing more participants at 4 mg/kg and new enrollment at 2 mg/kg, and the Phase 3 HARBOR trial started in May 2024.