Novartis (SWX: NOVN.SW) reported that delpacibart braxlosiran (del-brax), its investigational antibody oligonucleotide conjugate (AOC) for facioscapulohumeral muscular dystrophy (FSHD), met both the primary and key secondary endpoints in the biomarker cohort of the Phase I/II FORTITUDE study. Ther result means del-brax remains on course as the only clinical-stage candidate with demonstrated disease-modifying potential for FSHD, a condition with no specific approved therapies. The trial data, which showed reductions in two biomarkers linked to DUX4 pathway activity and muscle damage, support the dosing regimen already deployed in a pivotal Phase III study, with Novartis also planning to engage global regulators on the Phase I/II dataset. Del-brax was acquired as part of Novartis's purchase of Avidity Biosciences, completed in February 2026, and represents the most advanced asset in a trio of AOC-based neuromuscular programs that formed the strategic rationale for that transaction.
The FORTITUDE Phase I/II study is a randomized, double-blind, placebo-controlled trial enrolling 90 patients with FSHD across three dose cohorts. The data reported on June 11 pertain to Cohort C, a biomarker cohort of 51 patients aged 16–70 treated with del-brax 2 mg/kg every six weeks versus placebo for 12 months — the dose and schedule selected based on earlier dose-escalation cohorts and carried forward into the Phase III program.
The primary endpoint — change from baseline in plasma KHDC1L (cDUX), a circulating biomarker regulated by DUX4 — was met, indicating target engagement at the molecular level. The key secondary endpoint, change from baseline in creatine kinase, a marker of active muscle damage, was also met. Novartis described the Cohort C findings as replicating the target engagement and downstream muscle protection observed in the earlier Cohorts A and B, results from which were presented at the 32nd FSHD International Research Congress in June 2025. The company did not disclose specific numerical reductions or p-values in this release. Safety was described as consistent with prior results, with no new signals identified.
The FSHD biomarker endpoint readout is notable because it directly informs the regulatory conversation Novartis now intends to pursue. The company stated it plans to discuss the totality of Phase I/II biomarker and clinical data with global regulatory agencies, while the FORTITUDE-3 Phase III study continues to enroll 200 patients aged 16–70. That confirmatory trial uses quantitative muscle testing as its primary endpoint in the US and the 10-meter walk/run test in Europe — functional measures that would be required to support full approval.