While Novartis’ antibody-oligonucleotide conjugate failed to significantly improve hand function in patients with myotonic dystrophy type 1, the asset nevertheless showed signs of clinical activity in secondary and exploratory measures.
Novartis’ investigational antibody-oligonucleotide conjugate del-desiran—one of the pharma’s main bounties from its $12 billion buyout of Avidity Biosciences last year—failed a late-stage study of myotonic dystrophy type 1, potentially giving competitors the opportunity to take the lead in this market.
Without providing specific data behind the miss, Novartis on Tuesday morning said that del-desiran did not significantly improve hand opening time, as monitored by video, in the Phase 3 HARBOR study. The trial enrolled nearly 160 patients with myotonic dystrophy type 1 (DM1) who were given either del-desiran or placebo.
Del-desiran is a "$12B disappointment,” Oppenheimer analysts told investors Tuesday morning. Novartis crashed 12% before the opening bell—a drop that also stems from Friday’s failure of pelacarsen, the company’s cholesterol-lowering therapy. In the Phase 3 study called Lp(a)HORIZON, pelacarsen failed to significantly lower cardiovascular risk versus placebo.
The two fails follow Novartis’ announcement of three deaths linked to its investigational CAR T therapy rapcabtagene autoleucel. The fatalities forced the pharma to suspend a slew of immunology and neurology studies for the asset.
Despite the primary del-desiran miss, Novartis detected “evidence of clinical activity” in HARBOR’s secondary and exploratory outcomes, though the pharma didn’t share further details behind this claim. The company plans to meet with regulators to determine the next best steps for del-desiran.
Novartis won over del-desiran in October 2025, when it acquired RNA biotech Avidity Biosciences in a $12 billion deal. The asset consists of an antibody that targets the transferrin receptor 1, commonly found on muscle cells, and an siRNA payload that tags for destruction mRNA molecules encoding a disease-causing protein called DMPK.
Novartis’ takeover of Avidity formally closed in February of this year. Months later, Novartis reported a Phase 1/2 win for the Avidity asset del-brax, another antibody-oligonucleotide conjugate that the pharma is developing for facioscapulohumeral muscular dystrophy. The early study, called FORTITUDE, showed that del-brax treatment significantly lowered the levels of a key disease biomarker.
Aside from del-desiran, the Avidity acquisition also gave Novartis del-brax, being studied for Duchenne muscular dystrophy, and a handful of preclinical assets for rare neuromuscular conditions.
With HARBOR’s failure on Tuesday, Dyne, which is advancing an antisense oligonucleotide candidate, now “claims frontrunner status” in the DM1 race, Jefferies told investors that same day. While the del-desiran stumble could have negative read through to the broader DM1 space, Dyne “still has a chance to succeed and even generate superior data,” the analysts noted.
Dyne’s DM1 bet is called z-basivarsen, which has “best-in-class potential” for this indication, the firm noted on Tuesday, pointing to the asset’s “stronger tissue penetration and better biodistribution.” Dyne’s strategy of seeking accelerated approval—versus Novartis’ approach of going for traditional approval—could also play to the biotech’s favor, Jefferies added.
Dyne emerged as an attractive buyout target in the weeks following Avidity’s acquisition. “We think any potential acquirers who were interested and missed out on [Avidity] could plausibly look to DYN,” Stifel wrote at the time, though no such bid has yet to surface. A Phase 1/2 study of z-basivarsen in DM1 is ongoing, with topline data set for early next year.
