Novartis Phase III HARBOR Study Misses Primary Endpoint in DM1

Novartis said on Setyembre 8, 2026 that the global Phase III HARBOR study evaluating delpacibart etedesiran (del-desiran) in people living with myotonic dystrophy type 1 (DM1) did not demonstrate statistically significant improvement versus placebo on the primary endpoint of video hand opening time (vHOT), a novel measure of hand myotonia.

The disclosure was issued from Basel as an ad hoc announcement pursuant to Article 53 of the Swiss listing rules. Novartis said evidence of clinical activity in secondary endpoints and exploratory analyses was observed, and that safety findings from HARBOR were generally consistent with previously reported data. The company is evaluating the full HARBOR dataset and will engage with health authorities 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 at Novartis. Aradhye said that developing therapies for a complex disease like DM1 remains challenging and that setbacks are part of scientific progress. He said the company remains committed to identifying the most appropriate development path for the del-desiran program and to advancing innovative approaches for people living with DM1 and other serious neuromuscular diseases.

DM1 is a progressive, multisystem, heterogeneous neuromuscular disease caused by an expansion of CTG repeats in the DM1 protein kinase (DMPK) gene. People living with DM1 may experience a range of internal and systemic symptoms, including myotonia, muscle weakness and impaired hand function, which can affect everyday activities, independence and quality of life.

Del-desiran is an investigational antibody oligonucleotide conjugate (AOC) designed to target the underlying cause of DM1. The therapy consists of a muscle-targeting monoclonal antibody that binds to transferrin receptor 1 (TfR1) and is conjugated to a small interfering RNA (siRNA) designed to induce degradation of disease-causing toxic DMPK messenger RNA (mRNA). Del-desiran has received Orphan Drug, Fast Track and Breakthrough Therapy designations from the US Food and Drug Administration, and Orphan Medicinal Product Designation in the European Union.

The HARBOR Study

HARBOR is a global Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of del-desiran over 54 weeks in approximately 150 people living with DM1, according to the company. Participants were randomized to receive del-desiran or placebo every eight weeks. The primary endpoint is vHOT, and key secondary endpoints include 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 measured by the 10-meter walk/run test.

The study’s ClinicalTrials.gov record, under identifier NCT06411288, lists Avidity Biosciences as lead sponsor and carries the official title “A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Global Study to Evaluate the Efficacy and Safety of Intravenous AOC 1001 for the Treatment of Myotonic Dystrophy Type 1.” The record shows the study began on Mayo 30, 2024, reached its primary completion date on Hulyo 23, 2026, and was marked completed on Hulyo 29, 2026, with actual enrollment of 159 participants.

Per the registry entry, participants received an intravenous infusion of del-desiran or placebo every eight weeks for a total of seven doses, with the final dose at Week 48 and a final assessment at Week 54, following a screening period of up to six weeks. The study enrolled participants aged 16 to 65 with a clinical and genetic diagnosis of DM1, defined by a CTG repeat count of at least 100, who could walk independently for at least 10 meters at screening. Listed trial sites span the United States, Canada, Denmark, France, Germany, Italy, Japan, the Netherlands, Spain and the United Kingdom. The entry also states that participants completing the Week 54 assessments had the option to enroll in an open-label extension study, pending regulatory approval, and that an independent data monitoring committee reviewed safety, tolerability and efficacy data at regular intervals.

AOC Pipeline and Financial Guidance

Novartis said del-desiran is one of three antibody oligonucleotide conjugate therapies added to its neuromuscular pipeline through the acquisition of Avidity Biosciences. The company is advancing delpacibart zotadirsen (del-zota) in patients with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44). It has filed del-zota for accelerated approval and was granted priority review designation by the FDA. Novartis also plans to meet with the FDA on next steps for delpacibart braxlosiran (del-brax) in facioscapulohumeral muscular dystrophy (FSHD), which the company said is based on recent positive Phase I/II biomarker data.

Alongside the HARBOR result, Novartis said it maintains its five-year sales compound annual growth rate guidance of 5 to 6 percent for 2025 through 2030.