Novartis has announced that the biomarker cohort of the FORTITUDE phase 1/2 study of del-brax met its primary and key secondary endpoints, with reductions in KHDC1L (cDUX) and creatine kinase biomarker levels indicating both strong target engagement and reduction in muscle damage in patients with facioscapulohumeral muscular dystrophy (FSHD).

Del-brax is an investigational Antibody Oligonucleotide Conjugate (AOC)–a new class of RNA therapeutics–showing potential to become the first disease-modifying treatment for FSHD, a rare, irreversible neuromuscular disease marked by relentless loss of muscle function and progressive disability.

Nazem Atassi, Global Head, Neuroscience and Gene Therapy Development, Novartis, said, “The FORTITUDE biomarker cohort data importantly replicate the target engagement and downstream muscle protection seen with del-brax in earlier dose-escalation cohorts. These results validate the dosing regimen implemented in our phase 3 trial and lend further evidence of the potential for del-brax to have a significant impact for people with FSHD. We are now evaluating the totality of the biomarker and clinical data and look forward to discussions with global regulatory agencies as we work with urgency to advance the development of del-brax for patients in need.”

Del-brax is designed to address the root cause of FSHD, the aberrant expression of DUX4. Combining the tissue specificity of monoclonal antibodies with the precision of oligonucleotides, the AOC platform enables targeted delivery of siRNA to suppress DUX4 expression in previously hard-to-reach muscle cells of FSHD patients. Del-brax is the only investigational agent showing disease-modifying potential for FSHD in clinical studies. This investigational therapy has received FDA orphan drug and fast track designations, and EMA orphan drug designation, and is currently in phase 3 development.

Del-brax is 1 of 3 potential first-in-class, late-stage, disease-modifying AOC therapies added to the Novartis neuroscience pipeline through the acquisition of Avidity Biosciences completed in February 2026.

Beyond del-brax for FSHD, the Avidity acquisition included delpacibart-etedesiran (del-desiran) in phase 3 development for myotonic dystrophy type 1 (DM1), a rare progressive neuromuscular disorder with a poor prognosis and no disease-modifying therapies; and delpacibart-zotadirsen (del-zota) in phase 2 development for Duchenne Muscular Dystrophy (DMD), a severe, early-onset disease marked by progressive muscle damage and reduced life expectancy. Together, these programs build on Novartis’ expertise in spinal muscular atrophy, creating an industry-leading neuromuscular pipeline.