Novartis delpacibart braxlosiran (del-brax) Phase I/II study in facioscapulohumeral muscular dystrophy (FSHD) meets primary biomarker endpoint

Novartis reported positive results from the Phase I/II FORTITUDE study for delpacibart braxlosiran (del-brax), an investigational antibody oligonucleotide conjugate (AOC) targeting facioscapulohumeral muscular dystrophy (FSHD). The biomarker cohort demonstrated reductions in KHDC1L (cDUX) and creatine kinase levels, indicating strong target engagement and reduced muscle damage. Del-brax, designed to suppress DUX4 expression, is the first investigational therapy showing disease-modifying potential in FSHD clinical trials. The study included 90 patients across three dose cohorts, with the first two evaluating 2 mg/kg and 4 mg/kg doses against placebo. Results confirmed safety and dose selection for the ongoing Phase III trial, which is currently enrolling participants. Novartis plans to discuss the data with global regulatory authorities to advance del-brax’s development. FSHD, a progressive neuromuscular disease, affects approximately 45,000 to 87,000 people in the US and EU, causing irreversible muscle loss and disability. Del-brax’s mechanism combines monoclonal antibodies with siRNA to target muscle cells, offering a potential first disease-modifying treatment. The drug has received FDA Orphan Drug and Fast Track designations, as well as EMA Orphan Drug designation. Del-brax was acquired through Novartis’ February 2026 purchase of Avidity Biosciences, which also included late-stage AOC therapies for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD). These programs expand Novartis’ neuromuscular pipeline, building on its expertise in spinal muscular atrophy. The Phase I/II FORTITUDE trial (NCT05747924) was a randomized, double-blind, placebo-controlled study assessing safety, tolerability, and efficacy. Novartis will now evaluate the full dataset to support regulatory discussions and accelerate access for FSHD patients.