Novartis’ del-desiran failed to significantly improve the primary endpoint in the Phase 3 HARBOR trial in myotonic dystrophy type 1, despite evidence of clinical activity.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Novartis’ delpacibart etedesiran (del-desiran) did not meet the primary endpoint in the global Phase 3 HARBOR study, dealing a setback to the development of a targeted RNA therapy for myotonic dystrophy type 1 (DM1), a progressive neuromuscular disease with no approved treatment options. The company said the trial showed evidence of clinical activity across secondary endpoints and exploratory analyses and will assess the complete dataset before determining the program’s next steps.
Targeting the Molecular Cause of DM1
DM1 is caused by an expansion of CTG repeats in the DMPK gene. The resulting toxic RNA disrupts cellular processes and contributes to myotonia, muscle weakness, impaired hand function and broader systemic complications.
Del-desiran is an antibody oligonucleotide conjugate (AOC) that targets this underlying RNA pathology. Its muscle-targeting antibody binds transferrin receptor 1 (TfR1), enabling delivery of a small interfering RNA (siRNA) payload into muscle cells. The siRNA promotes degradation of toxic DMPK messenger RNA, with the goal of reducing the molecular driver of disease.
The therapy has received Orphan Drug, Fast Track and Breakthrough Therapy designations from the US Food and Drug Administration (FDA), as well as Orphan Medicinal Product designation in the European Union.
HARBOR Results and Trial Design
HARBOR (NCT06411288) enrolled approximately 150 people with DM1 in a randomized, double-blind, placebo-controlled Phase 3 study. Participants received del-desiran or placebo every eight weeks for 54 weeks.
The primary endpoint was video hand opening time, or vHOT, a functional measure of myotonia that assesses how quickly patients can open their hands after sustained contraction. Del-desiran did not produce a statistically significant improvement versus placebo on this endpoint.
Novartis reported evidence of clinical activity in secondary endpoints and exploratory analyses but did not disclose detailed numerical results in the topline update. Key secondary measures included hand grip strength, quantitative muscle testing, activities of daily living assessed by DM1-Activ, and mobility and physical function measured by the 10-meter walk/run test.
Safety findings were generally consistent with previously reported data, with no new safety signal highlighted in the announcement.
Development Path Remains Under Review
The HARBOR outcome adds uncertainty to del-desiran’s regulatory path, but Novartis has not discontinued the program. The company is reviewing the full dataset and plans to engage health authorities before deciding whether and how to continue development.
Shreeram Aradhye, Novartis’ President, Development and Chief Medical Officer, acknowledged the difficulty of developing treatments for a complex disease such as DM1 and said the company remains committed to identifying an appropriate development path for del-desiran.
AOC Pipeline Advances Despite HARBOR Setback
Del-desiran is one of three AOC programs Novartis acquired through its acquisition of Avidity Biosciences. The broader platform continues to progress despite the HARBOR result.
Novartis has filed delpacibart zotadirsen (del-zota) for accelerated approval in Duchenne muscular dystrophy patients with mutations amenable to exon 44 skipping (DMD44), with the FDA granting priority review.
The company also plans to meet with the FDA regarding delpacibart braxlosiran (del-brax) in facioscapulohumeral muscular dystrophy (FSHD), following positive Phase 1/2 biomarker data.
Novartis said it is maintaining its five-year sales CAGR guidance of 5% to 6% for 2025–2030, indicating that the HARBOR setback has not changed its broader financial outlook.
Reference
Novartis provides update on delpacibart etedesiran (del-desiran) Phase III HARBOR study for the treatment of myotonic dystrophy type 1 (DM1), Novartis, 08 September 2026
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.