Phase 3 setback for first-in-class myotonic dystrophy therapy

Novartis reported that the phase 3 HARBOR trial of delpacibart etedesiran (del-desiran) did not demonstrate a statistically significant improvement over placebo in its primary endpoint, video hand opening time (a novel measure of hand myotonia) in patients with myotonic dystrophy type 1 (DM1).

DM1 is a progressive, multisystem disorder with no approved disease-modifying treatment. Del-desiran is designed to address its underlying biology by delivering small interfering RNA to muscle and reducing toxic DMPK messenger RNA. Failure on the primary endpoint means these topline findings are unlikely to change current practice or support an uncomplicated regulatory path. They may also prompt scrutiny of endpoint selection, treatment duration, and patient heterogeneity in future DM1 trials.

The global, double-blind study enrolled approximately 150 patients and evaluated treatment every 8 weeks over 54 weeks. Novartis reported evidence of clinical activity across secondary endpoints and exploratory analyses, with safety findings generally consistent with earlier data. However, the company did not disclose effect sizes, statistical results, or which secondary outcomes (including grip strength, quantitative muscle testing, daily functioning, and mobility) showed benefit.

The company says it will analyze the complete dataset and consult health authorities before determining the program’s future. The setback does not necessarily invalidate the broader antibody-oligonucleotide conjugate platform: related candidates for exon 44–amenable Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy continue advancing on separate clinical and regulatory evidence.

Source: Novartis. (2026 Sep 8). Novartis provides update on delpacibart etedesiran (del-desiran) Phase III HARBOR study for the treatment of myotonic dystrophy type 1 (DM1)