Novartis Phase III Study for Del-desiran Fails Primary Endpoint in DM1 Treatment

Novartis, a leading pharmaceutical company, announced on September 8, 2026, that its Phase III HARBOR study for del-desiran, an investigational antibody oligonucleotide conjugate (AOC) designed to treat myotonic dystrophy type 1 (DM1), did not meet its primary endpoint. The study, evaluating the efficacy and safety of del-desiran over 54 weeks, found no statistically significant improvement in hand opening time (vHOT) compared to a placebo. Despite this setback, the company observed evidence of clinical activity in secondary endpoints and exploratory analyses.

DM1 is a progressive, multisystem, heterogeneous neuromuscular disease characterized by an expansion of CTG repeats in the DMPK gene. Patients living with DM1 often experience myotonia, muscle weakness, and impaired hand function, significantly impacting their daily lives. Del-desiran, one of three AOC therapies added to Novartis' neuromuscular pipeline through the acquisition of Avidity Biosciences, received Orphan Drug, Fast Track, and Breakthrough Therapy Designations from the US Food and Drug Administration (FDA) and Orphan Medicinal Product Designation in the European Union.

The HARBOR study, which enrolled approximately 150 participants, assessed the impact of del-desiran on multiple functional aspects of DM1. The primary endpoint was vHOT, a novel measure of hand myotonia, while key secondary endpoints included muscle strength as measured by hand grip strength and quantitative muscle testing (QMT) total score, activities of daily living as measured by the DM1-Activ, and mobility and physical function as measured by the 10-meter walk/run test (10mWRT).

Despite the primary endpoint not being met, the company noted consistent safety findings from HARBOR, in line with previously reported data. Novartis will now evaluate the full HARBOR dataset to determine the most appropriate development path for del-desiran. "Despite decades of research, there are still no approved treatment options for DM1, and patients and caregivers continue to face a significant daily burden," said Shreeram Aradhye, President, Development and Chief Medical Officer, Novartis. "Developing therapies for a complex disease like DM1 remains challenging, and setbacks are part of scientific progress."

In other developments, del-desiran is part of Novartis' AOC pipeline, alongside delpacibart zotadirsen (del-zota) and delpacibart braxlosiran (del-brax). Del-zota is being advanced in patients with Duchenne muscular dystrophy (DMD) with mutations amenable to exon 44 skipping, and the company has filed for accelerated approval with the FDA, which granted a priority review designation. Del-brax is expected to meet with the FDA based on recent positive Phase I/II biomarker data.

Novartis maintains its five-to-six percent five-year sales compound annual growth rate (CAGR) guidance for 2025-2030, reflecting its commitment to advancing innovative approaches for people living with DM1 and other serious neuromuscular diseases. The company continues to expand its legacy of innovation in neurology, focusing on spinal muscular atrophy (SMA), multiple sclerosis (MS), and neuromuscular diseases.