Novartis’ neuromuscular RNA therapeutics program ran into a major setback as delpacibart etedesiran (del-desiran) failed to hit its primary endpoint in the pivotal HARBOR Phase III trial, according to the company’s disclosure summarized by Reuters. The study missed statistically significant improvement versus placebo in video Hand Opening Time (vHOT) through week 54. The failure adds pressure to Novartis’ broader strategy following its Avidity Partners acquisition, which was positioned as a way to bolster the neuroscience pipeline with multiple late-stage programs in a new class of RNA therapeutics. Investors have already been publicly critical of the board’s acquisition oversight, Reuters reports. Del-desiran is designed to target the underlying cause of myotonia in myotonic dystrophy type 1 (DM1), using an antibody-oligonucleotide conjugate (AOC) approach to deliver RNA to muscle tissue via TfR1 targeting. With a negative trial outcome, the risk-return balance for this platform is now under sharper scrutiny.