Novartis Del-Desiran Phase III Trial Misses Primary Endpoint; 2025-2030 Sales Outlook Unchanged

Novartis said on September 8 that its Phase III HARBOR trial of delpacibart etedesiran, or del-desiran, in myotonic dystrophy type 1 failed to show a statistically significant improvement versus placebo on the study’s primary endpoint. The Swiss drugmaker nevertheless maintained its five-year sales outlook of 5% to 6% compound annual growth from 2025 through 2030 in constant currencies.

The topline result is a setback for one of the late-stage neuromuscular programs Novartis acquired with Avidity Biosciences earlier this year, but it does not by itself end development of the drug. Novartis said it saw evidence of clinical activity across secondary endpoints and exploratory analyses, while safety findings were generally consistent with previously reported data. The company has not yet disclosed the numerical secondary-endpoint results or said what regulatory path, if any, it will pursue.

In its September 8 HARBOR update, Novartis said it is evaluating the full dataset and plans to engage with health authorities before deciding the most appropriate development path for del-desiran. That distinction matters because the announcement establishes a failed primary efficacy endpoint, but it does not provide enough detail to determine whether the secondary signals could support further trials, a modified development strategy or regulatory discussions.

HARBOR misses vHOT as Novartis reviews the full dataset

HARBOR was designed as a global, randomized, double-blind, placebo-controlled Phase III study over 54 weeks in approximately 150 people with myotonic dystrophy type 1, or DM1. Participants received del-desiran or placebo every eight weeks. The ClinicalTrials.gov record for HARBOR identifies the trial as NCT06411288 and describes it as a pivotal efficacy and safety study of intravenous del-desiran in DM1.

The primary endpoint was video hand opening time, or vHOT, a measure of hand myotonia. Novartis said del-desiran did not demonstrate a statistically significant improvement against placebo on that measure. Key secondary endpoints included hand grip strength, quantitative muscle testing total score, the patient-reported DM1-Activ measure of daily living, and the 10-meter walk/run test for mobility and physical function.

Novartis described the secondary and exploratory findings only as showing evidence of clinical activity. The company did not publish effect sizes, confidence intervals or p-values for those measures in the topline release. As a result, the strength and consistency of those signals cannot yet be judged from the public announcement. Safety findings were also summarized at a high level, with Novartis saying they were generally consistent with previously reported data.

DM1 is a progressive neuromuscular disorder caused by an expansion of CTG repeats in the DMPK gene. Symptoms can include myotonia, muscle weakness and impaired hand function, along with broader effects across multiple body systems. Novartis said there are no approved treatment options for the disease. Del-desiran is designed to address the underlying biology through an antibody oligonucleotide conjugate that combines a muscle-targeting antibody with small interfering RNA intended to reduce disease-causing toxic DMPK messenger RNA.

The investigational medicine had already received Orphan Drug, Fast Track and Breakthrough Therapy designations from the U.S. Food and Drug Administration, as well as Orphan Medicinal Product designation in the European Union. Those designations can facilitate development or regulatory interaction, but they do not substitute for evidence from a successful pivotal trial. The missed HARBOR primary endpoint therefore leaves Novartis with a materially more complicated evidence package than the company would have had after a positive Phase III result.

Avidity acquisition gives the result a wider pipeline context

Del-desiran entered Novartis through its acquisition of Avidity Biosciences, completed on February 27. Novartis paid $72 per Avidity share in cash, valuing the company at about $12 billion on a fully diluted basis and about $11 billion on an enterprise-value basis. Avidity became an indirect wholly owned subsidiary of Novartis, bringing with it a muscle-directed antibody oligonucleotide conjugate platform and three late-stage neuromuscular programs.

The other two programs remain active. Delpacibart zotadirsen, or del-zota, is being developed for Duchenne muscular dystrophy in patients with mutations amenable to exon 44 skipping. Novartis said it filed del-zota for accelerated approval and received FDA priority review. Delpacibart braxlosiran, or del-brax, is being developed for facioscapulohumeral muscular dystrophy, and Novartis plans to meet with the FDA on next steps after positive Phase I/II biomarker data.

That broader portfolio is important when interpreting the HARBOR result. At the time the Avidity acquisition closed, Novartis said the acquired platform and three late-stage programs could support its 2025-2030 growth outlook and create potential product-launch opportunities before 2030. The September 8 update does not withdraw that portfolio-level thesis, but it clearly weakens the evidence for one of the three programs that helped support it.

The result also illustrates the development risk embedded in late-stage biotechnology acquisitions. A Phase III asset can carry substantial strategic and financial value before a pivotal readout, yet a missed primary endpoint can sharply change the range of realistic regulatory and commercial outcomes. In this case, Novartis has not written off del-desiran, and it has not said how much value or future sales it had assigned to the medicine within its planning assumptions. Any attempt to quantify the financial effect of the HARBOR miss from the topline release alone would therefore go beyond the disclosed evidence.

Five-year sales guidance remains 5% to 6%

Novartis first rolled forward its mid-term sales guidance in November 2025, projecting 5% to 6% compound annual sales growth in constant currencies from 2025 through 2030. That outlook was built around a broad set of in-market growth drivers and a pipeline of more than 30 potential high-value medicines, rather than a single development program. The company said at the time that more than 15 potentially submission-enabling readouts were expected over the following two years.

The latest financial results also show why the guidance spans a wider business than the Avidity pipeline. In the second quarter of 2026, Novartis reported net sales of $14.4 billion, up 1% in constant currencies, while first-half sales were $27.5 billion, down 2% in constant currencies. Growth from products including Kisqali, Kesimpta, Pluvicto, Scemblix and Leqvio was offset in part by generic competition affecting older medicines. In July, the company reaffirmed full-year 2026 guidance for low-single-digit net sales growth and a low-single-digit decline in core operating income, both in constant currencies.

Against that backdrop, the September 8 statement that the 2025-2030 sales CAGR guidance remains unchanged is a portfolio-level message. Novartis did not provide a revised probability of success for del-desiran, a new peak-sales estimate for the drug or a quantified adjustment to the assumptions behind the five-year outlook. Keeping the guidance therefore should not be read as evidence that the HARBOR miss has no economic effect. It means the company currently believes its broader set of marketed products and pipeline assets can still support the stated growth range.

The next material step for del-desiran is more specific. Novartis said it will complete its analysis of the HARBOR data and engage with health authorities to determine the program’s development path. Until that work is disclosed, the verified topline picture is limited but consequential: the primary Phase III endpoint was missed, some secondary and exploratory activity was observed without numerical detail, and Novartis has kept its 2025-2030 sales growth outlook unchanged.