Novartis falls sharply on another major R&D setback

Hard on the heels of a big disappointment in its cardiovascular pipeline, Novartis has suffered another – this time for its highly anticipated neuromuscular disease therapy del-desiran.

The company's already weakened share price lost another 9% in value this morning, after it reported that del-desiran (delpacibart etedesiran) failed to show efficacy in myotonic dystrophy type 1 (DM1), which currently has no approved disease-modifying therapies.

The HARBOR trial missed its primary endpoint, as del-desiran was unable to show a significant improvement over placebo on the primary efficacy endpoint, video hand opening time (vHOT). DM1 is characterised by myotonia of the hands, a condition in which muscles cannot relax quickly after they contract, and vHOT is a measure of that symptom.

Del-desiran is one of three antibody-oligonucleotide conjugate (AOC) therapies added to the Novartis neuromuscular pipeline through its $12 billion acquisition of Avidity Bio last year, and has been trumpeted by Novartis as a potential $5 billion-a-year blockbuster.

While Novartis isn't giving up on del-desiran yet – pointing to "evidence of clinical activity in secondary endpoints and exploratory analyses" – analysts said the outcome could dent confidence in other AOCs acquired with Avidity.

Those are delpacibart zotadirsen (del-zota) for Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44), in the phase 3 AAFARI4 trial due to complete in 2029, and delpacibart braxlosiran (del-brax), which recently generated positive phase 1/2 data in facioscapulohumeral muscular dystrophy (FSHD).

The del-desiran miss means that two of Novartis' three most important data readouts this year have been a bust, coming shortly after Lp(a)-targeted pelacarsen failed to reduce cardiovascular risks in a major phase 3 trial. On the plus side, it did report positive phase 3 results with oral BTK inhibitor remibrutinib in multiple sclerosis, setting up regulatory filings.

"Developing therapies for a complex disease like DM1 remains challenging, and setbacks are part of scientific progress," said Novartis' chief medical officer, Shreeram Aradhye.

"As we continue to evaluate the full HARBOR dataset, we remain committed to identifying the most appropriate development path for the del-desiran programme and advancing innovative approaches for people living with DM1 and other serious neuromuscular diseases," he added.

Despite the setbacks, the company has maintained its prediction of 5%-6% in compound annual revenue growth 2025-2030, a period that encompasses patent expiries for big-selling products like heart failure therapy Entresto (sacubitril/valsartan), blood cancer therapy Jakavi (ruxolitinib) and immunology blockbuster Cosentyx (secukinumab).