Del-Desiran Misses Primary Endpoint in Phase 3 HARBOR Trial for Myotonic Dystrophy Type 1

The phase 3 HARBOR trial of investigational delpacibart etedesiran (del-desiran; Novartis, Basel, Switzerland) did not meet its primary endpoint in people with myotonic dystrophy type 1 (DM1). Treatment did not demonstrate a statistically significant improvement over placebo in video hand opening time (vHOT), a novel measure of hand myotonia. Novartis reported evidence of clinical activity on secondary endpoints and exploratory analyses but has not disclosed numerical results for those outcomes.

HARBOR (NCT06411288) is a global, phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of del-desiran over 54 weeks in approximately 150 participants with DM1. Participants were randomized to receive del-desiran or placebo every 8 weeks. The primary endpoint was vHOT. Key secondary endpoints included muscle strength measured by hand grip strength and quantitative muscle testing (QMT) total score, activities of daily living measured by DM1-Activ, and mobility and physical function assessed using the 10-meter walk/run test.

What the HARBOR Results Showed

• Primary endpoint: Del-desiran did not significantly improve vHOT compared with placebo.
• Secondary outcomes: Novartis reported evidence of clinical activity across secondary endpoints and exploratory analyses but did not provide effect sizes or statistical results.
• Safety: Findings were generally consistent with previously reported safety data for del-desiran.
• Next steps: Novartis is analyzing the complete dataset and plans to engage with health authorities before determining the program’s development path.

Del-desiran is an antibody oligonucleotide conjugate designed to address the underlying molecular cause of DM1, a progressive, multisystem neuromuscular disorder caused by expanded CTG repeats in the DMPK gene. The therapy combines a muscle-targeting monoclonal antibody that binds transferrin receptor 1 with a small interfering RNA designed to induce degradation of toxic DMPK messenger RNA.

Del-desiran has received Orphan Drug, Fast Track, and Breakthrough Therapy designations from the Food and Drug Administration (FDA), as well as Orphan Medicinal Product designation in the European Union. The therapy remains investigational and is not FDA approved for DM1.

Clinical Application for Neurologists

For clinicians managing DM1, the HARBOR announcement does not establish a clinical benefit for del-desiran because the trial did not meet its prespecified primary endpoint. Although activity on secondary and exploratory outcomes was reported, the clinical relevance of those findings cannot be fully assessed without detailed efficacy data and statistical analyses. These results will be particularly important given the multisystem nature of DM1 and the absence of approved therapies targeting the underlying disease.

For practicing neurologists, del-desiran therefore remains an investigational option rather than a therapy that changes current DM1 management. The complete HARBOR results—including the magnitude and consistency of effects across muscle strength, daily function, and mobility measures—will provide additional context for assessing the program. Novartis is reviewing the full dataset and plans to consult with health authorities before determining the next steps for del-desiran.

Source

Novartis. Novartis provides update on delpacibart etedesiran (del-desiran) Phase III HARBOR study for the treatment of myotonic dystrophy type 1 (DM1). Press release. Published September 8, 2026. https://www.novartis.com/news/media-releases/novartis-provides-update-delpacibart-etedesiran-del-desiran-phase-iii-harbor-study-treatment-myotonic-dystrophy-type-1-dm1