Novartis核心DM1药物del-desiran三期HARBOR研究未达主要终点

The phase 3 Harbor trial of Novartis’ del-desiran has missed its primary endpoint, dealing a major blow to an asset that the Swiss drugmaker acquired in the $12 billion takeover of Avidity Biosciences. The flop leaves Novartis with one win and two failures from a rapid-fire run of key clinical readouts.
Success for del-desiran, an antibody oligonucleotide conjugate, in the rare muscle-wasting disease myotonic dystrophy type 1 (DM1) was “crucial” for validating the Avidity deal, Guggenheim Securities analysts said in a note to investors last month. The analysts framed the Harbor readout as part of a set of three events in the second half of 2026 that will shape Novartis’ growth beyond 2030.
Novartis started the run of three readouts with a win for Rhapsido in relapsing multiple sclerosis, only for pelacarsen to fail a cardiovascular disease trial and del-desiran to flunk its DM1 test. The readouts were “important for gaining confidence in Novartis’ mid- and long-term sales potential,” the analysts said.
The failure of the Harbor trial raises doubts about del-desiran’s ability to contribute to sales. In the trial of 159 patients, del-desiran was statistically no better than placebo at improving video hand opening time (vHOT). Novartis used vHOT to assess the effect of seven doses of del-desiran, infused every eight weeks, on the delayed muscle relaxation that affects people with DM1.
Noting evidence of clinical activity in secondary endpoints and exploratory analyses, the company will analyze the full dataset and talk to health authorities to determine the next steps. Novartis is committed “to identifying the most appropriate development path,” Chief Medical Officer Shreeram Aradhye, M.D., said in a statement. Aradhye also reiterated Novartis’ commitment to developing treatments for DM1.
Novartis acquired two other late-stage neuromuscular programs in the Avidity buyout. The company has filed for accelerated approval of delpacibart zotadirsen in Duchenne muscular dystrophy and plans to meet with the FDA to discuss the next steps for delpacibart braxlosiran in facioscapulohumeral muscular dystrophy (FSHD). The planned talks center on recent positive phase 1/2 data in FSHD.
Yet del-desiran was central to the Avidity deal. When Novartis disclosed the takeover, the pharma presented external forecasts showing (PDF) peak annual del-desiran revenues as high as $6 billion, making DM1 the largest of the opportunities unlocked by the Avidity acquisition. FSHD is another multi-blockbuster opportunity, Novartis said, but as of October even the most optimistic analysts had sales peaking around $4 billion.