Novartis took another major hit to its late-stage pipeline as delpacibart etedesiran failed to meet the primary endpoint in the pivotal Phase 3 HARBOR trial in myotonic dystrophy type 1 (DM1). In the study, the antibody–oligonucleotide conjugate did not achieve statistically significant improvement versus placebo in video Hand Opening Time through week 54. The setback adds to a rapid sequence of failures for the company, following the Phase 3 cardiovascular outcomes failure of pelacarsen (Lp(a)HORIZON) in collaboration with Ionis Pharmaceuticals. Pelacarsen missed the primary endpoint of reducing cardiovascular events versus placebo in a composite of cardiovascular death, non-fatal MI, non-fatal stroke, and urgent revascularization. Novartis said it is evaluating the full HARBOR dataset to determine the most appropriate development path and plans to engage with authorities. The combination of DM1 and Lp(a) failures raises uncertainty around near-term value capture from targeted precision approaches in cardiovascular and neuromuscular disease.