Novartis muscle disease drug fails, capping third trial setback in a week

Novartis ↗ 0.27% disclosed Tuesday that its experimental drug del-desiran failed to outperform placebo in a pivotal study for the rare muscle-wasting disease myotonic dystrophy type 1, marking the company's third clinical trial setback in roughly a week.

The Phase 3 HARBOR trial, which enrolled approximately 150 patients, tested whether del-desiran could improve hand muscle function in people with DM1, a condition that causes progressive muscle stiffness and weakness and has no approved treatments. The drug did not meet its primary endpoint of improving video hand opening time, or vHOT, a measure of how quickly a patient's hand can relax after squeezing. Novartis said the study did show "evidence of clinical activity in other measures" and that it would evaluate the full dataset and engage with regulators on a development path forward.statnews+1

A Turbulent Week

The del-desiran result caps a period of unusual turbulence for the Swiss drugmaker. On September 1, Novartis paused enrollment in trials of rapcabtagene autoleucel, an experimental CAR-T cell therapy for autoimmune diseases, after three patients died during the studies. Days later, on September 4, the company reported that pelacarsen, a once-promising cardiovascular drug, failed to reduce the risk of heart attacks, strokes, and cardiovascular death in the 8,323-patient Phase 3 Lp(a)HORIZON trial. While pelacarsen succeeded in lowering levels of lipoprotein(a), a genetic risk factor linked to heart disease, that reduction did not translate into fewer adverse cardiovascular events compared to placebo.novartis+4

Pipeline Pressure Mounts

The string of failures is expected to intensify scrutiny of Novartis's pipeline and acquisition strategy as the company faces a looming patent cliff on several of its top-selling medicines. Del-desiran was originally developed by Avidity Biosciences, which Novartis acquired to bolster its position in RNA-based therapeutics.bloomberg+1

The week was not entirely bleak. On September 1, Novartis reported positive results from two Phase 3 trials of remibrutinib in relapsing multiple sclerosis, showing the oral drug cut relapse rates compared to an older treatment. But the sheer concentration of clinical disappointments — a halted cell therapy program, a failed cardiovascular blockbuster candidate, and now a missed endpoint in neuromuscular disease — poses a challenge for a company that has staked its future on pipeline-driven growth.reuters+1