Novartis is reassessing the development strategy for delpacibart etedesiran (del-desiran) after the investigational therapy failed to achieve the primary endpoint in a pivotal Phase III study involving patients with myotonic dystrophy type 1 (DM1).

The multinational HARBOR trial did not show a statistically significant improvement over placebo on video hand opening time (vHOT), a measure developed to assess hand myotonia. Despite the topline failure, Novartis reported signals of clinical activity in selected secondary measures and exploratory analyses.

The company said it will conduct a detailed review of the complete HARBOR dataset before determining how the del-desiran program will proceed. Novartis also plans to discuss the findings with regulatory authorities.

“Developing therapies for a complex disease like DM1 remains challenging, and setbacks are part of scientific progress,” says Shreeram Aradhye, President of Development and Chief Medical Officer at Novartis.

DM1 is a progressive inherited neuromuscular disorder caused by an expansion of CTG repeats in the DMPK gene. The disease can affect multiple organ systems, with manifestations including muscle weakness, myotonia and impaired hand function. There are currently no approved disease-modifying therapies for DM1, leaving considerable interest in approaches designed to address the molecular mechanisms underlying the disorder.

Del-desiran previously received Orphan Drug, Fast Track and Breakthrough Therapy designations from the US Food and Drug Administration, as well as Orphan Medicinal Product designation in the European Union.

While the HARBOR result represents a setback for the DM1 program, Novartis continues to advance other AOC candidates obtained through the Avidity transaction. Delpacibart zotadirsen (del-zota) is being developed for Duchenne muscular dystrophy in patients carrying mutations amenable to exon 44 skipping. The program has been submitted to the FDA for accelerated approval, with the agency granting the application priority review.

Novartis is also preparing for discussions with the FDA concerning delpacibart braxlosiran (del-brax), an investigational treatment for facioscapulohumeral muscular dystrophy (FSHD). The planned regulatory interaction follows positive biomarker findings from Phase I/II development.

Despite the HARBOR outcome, Novartis said the development setback does not alter its broader financial outlook. The company continues to expect five-year sales growth of approximately 5% to 6% annually between 2025 and 2030.

For del-desiran, the next phase will depend on the company’s analysis of the complete HARBOR results and subsequent discussions with regulators. The full dataset could provide additional context around the secondary and exploratory findings and help determine whether any aspect of the program warrants further clinical investigation.

For more information, visit www.novartis.com.