Novartis drug del-desiran fails phase 3 trial in myotonic dystrophy

Novartis has reported that del-desiran, an investigational RNA-targeted therapy for myotonic dystrophy type 1 (DM1), failed to meet its primary endpoint in the HARBOR phase 3 trial. The result represents the second major late-stage trial collapse for the company within a matter of days, according to reporting by STAT News.

Myotonic dystrophy type 1 is a dominantly inherited multisystem disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene. The expanded repeat produces toxic RNA that sequesters RNA-binding proteins, disrupting splicing across multiple tissues. Del-desiran was designed to reduce levels of the toxic DMPK transcript; the failure in HARBOR adds to a pattern of difficulty translating promising molecular mechanisms into clinical benefit in DM1.

The setback is notable for the rare-disease and neuromuscular genetics communities. Several other therapeutic approaches targeting DMPK RNA — including antisense oligonucleotides and small molecules — remain in earlier stages of development across competing programmes. Researchers and clinicians following the DM1 therapeutic landscape will be watching closely to understand whether the HARBOR failure reflects a target-biology problem, a patient-selection issue, or trial-design factors; those details have not yet been made publicly available by Novartis.

Full trial data are expected to be presented at an upcoming medical congress. STAT News notes that Novartis faces increasing pipeline pressure following this and its other recent trial collapse.