Novartis’ $12B Avidity bet suffers Phase 3 blow
Novartis has suffered another pipeline setback after del-desiran, an antibody-oligonucleotide conjugate acquired with Avidity Biosciences, failed to significantly improve hand function over placebo in the Phase 3 HARBOR study in myotonic dystrophy type 1.
What now: The Swiss drugmaker said it saw signs of clinical activity across secondary and exploratory endpoints and will analyse the full dataset before discussing the programme’s future with regulators.
Why it matters: The result is an early test of the roughly $12 billion (€10.3 billion) Avidity acquisition, completed in February. Del-desiran was not just another programme in the deal: it was its most advanced asset. Novartis bought Avidity not only for three late-stage programmes in rare muscle diseases, but for its antibody-oligonucleotide conjugate, or AOC, platform.
How it works: The technology combines an antibody targeting transferrin receptor 1, or TfR1, with an RNA payload. The antibody is designed to shuttle the payload into muscle cells, where siRNA or other oligonucleotides can alter disease-related RNA. Avidity has described its clinical work as the first demonstration of targeted systemic RNA delivery into muscle.
The big picture: That delivery capability is a major part of what made Avidity strategically attractive. Most established RNA medicines remain limited in the tissues they can efficiently reach, making extrahepatic delivery one of the central challenges in the field.
- AOCs aim to bridge that gap by combining the targeting ability of antibodies with the gene-silencing or RNA-modifying activity of oligonucleotides.
Yes, but: Avidity is not the only company exploring this option. US-based Dyne Therapeutics is developing its own TfR1-targeted FORCE conjugates, including DYNE-101 in DM1 and DYNE-251 in Duchenne muscular dystrophy. Other companies are pursuing AOC approaches in muscle diseases, cancer and other indications.
What’s next: For Novartis, the question is therefore larger than whether del-desiran can still find a regulatory path. The company needs to show that AOC delivery works as a platform and that targeting different RNAs can repeatedly translate into clinically meaningful effects.
- Two other major programmes from the acquisition now move further into the spotlight. Del-zota, targeting Duchenne muscular dystrophy in patients amenable to exon 44 skipping, is advancing toward regulatory submission. Novartis also plans discussions with the FDA on del-brax for facioscapulohumeral muscular dystrophy following positive biomarker data.
Bad timing for Novartis: The setback comes only days after pelacarsen, Novartis’ closely watched Lp(a)-lowering drug, failed to reduce cardiovascular events in the Phase 3 HORIZON study. It also follows the suspension this summer of several cell therapy trials after patient deaths. Meanwhile, Novartis is looking for new growth drivers as patent expirations put pressure on established products including Entresto.
- There has been some good news: remibrutinib recently delivered positive Phase 3 results in relapsing multiple sclerosis. Still, two of three closely watched recent clinical readouts — pelacarsen and del-desiran — have now disappointed. Analysts had described the del-desiran readout as particularly important for validating the Avidity acquisition.
Investors vote down: The market reaction was sharp: Novartis shares fell about 9% on Sept. 8, making it one of the company’s worst trading days in recent years.
- Despite the news, Novartis continues to forecast annual sales growth of 5% to 6% from 2025 through 2030 and has not abandoned del-desiran. The company plans to review the complete data and consult regulators on possible next steps.
