Novartis DM1 Candidate Misses Late-Stage Goal, Clouding Development Prospects

Novartis announced Tuesday that its experimental therapy for myotonic dystrophy type 1 (DM1) failed to achieve the primary goal of a late-stage clinical trial, a setback for patients who currently have no approved treatment options for the disease.

Delpacibart etedesiran (del-desiran) did not show a statistically significant improvement over placebo on the trial's main measure — video hand opening time, an indicator of hand muscle stiffness. The global Phase III HARBOR study enrolled approximately 150 people with DM1.

In the 54-week randomized, double-blind, placebo-controlled study, signs of clinical activity emerged on other measures and in additional analyses. The safety profile was generally consistent with previously disclosed data.

Novartis said it will assess the complete dataset and consult with health authorities to decide 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 of development and chief medical officer at Novartis.

"Developing therapies for a complex disease like DM1 remains challenging, and setbacks are part of scientific progress."

DM1 is a progressive neuromuscular condition caused by an expansion of CTG repeats — repeated sections of DNA — in the DM1 protein kinase gene.

Del-desiran is an antibody oligonucleotide conjugate, a drug intended to target and break down disease-causing DMPK messenger RNA, which carries the genetic instructions implicated in the disease.

It holds Orphan Drug, Fast Track, and Breakthrough Therapy designations from the U.S. Food and Drug Administration, along with Orphan Medicinal Product designation in the European Union.

Del-desiran is one of three antibody oligonucleotide conjugate therapies Novartis added to its neuromuscular pipeline through its acquisition of Avidity Biosciences.

The other two are advancing: delpacibart zotadirsen has been filed for accelerated FDA approval and granted priority review designation for Duchenne muscular dystrophy with mutations amenable to exon 44 skipping, while delpacibart braxlosiran is the subject of a planned FDA meeting on next steps for facioscapulohumeral muscular dystrophy, based on positive Phase I/II biomarker data.

Novartis said it maintains its five-year sales compound annual growth rate guidance of 5% to 6% for 2025 to 2030.