Novartis del-brax Achieves Phase I/II Primary Endpoint in FSHD, Phase III Enrolling

Positive biomarker data from Novartis's FORTITUDE Phase I/II study position del-brax (delpacibart braxlosiran) as the first investigational agent with disease-modifying potential in facioscapulohumeral muscular dystrophy, a finding that now anchors the company's regulatory engagement strategy and validates the dosing regimen already running in its Phase III programme.

The FORTITUDE biomarker cohort met its primary and key secondary endpoints, demonstrating statistically meaningful reductions in KHDC1L (cDUX) and creatine kinase levels. Those two markers serve as proxies for target engagement and downstream muscle protection, respectively, and their co-reduction replicates signals observed in earlier dose-escalation cohorts A and B, results first disclosed at the 32nd FSHD International Research Congress in June 2025. The safety profile was consistent with prior data.

Del-brax is an antibody oligonucleotide conjugate (AOC), a modality that pairs monoclonal antibody tissue specificity with siRNA precision to suppress aberrant DUX4 expression in muscle cells that have historically been difficult to reach with oligonucleotide therapeutics. The Cohort C dosing regimen of 2 mg/kg every six weeks, selected on the basis of earlier cohort data, is the regimen now running in the Phase III trial. For CMC and process development teams, that dose-regimen lock is a meaningful milestone: it narrows the manufacturing envelope ahead of any Phase III-to-commercial scale-up discussions.

Del-brax carries FDA Orphan Drug and Fast Track designations and EMA Orphan Drug designation. Novartis has stated it will engage global regulatory authorities on the Phase I/II dataset, a step that typically precedes pre-NDA or scientific advice meetings and can shape the evidentiary requirements placed on Phase III endpoints. FSHD affects an estimated 45,000 to 87,000 patients across the US and EU, a population size that will inform both the commercial manufacturing scale and any post-approval pharmacovigilance obligations.

Del-brax is one of three late-stage AOC programmes that entered the Novartis neuroscience pipeline through the Avidity Biosciences acquisition completed in February 2026. The other two, del-desiran (Phase III, myotonic dystrophy type 1) and del-zota (Phase II, Duchenne muscular dystrophy), share the AOC platform, meaning that process development and analytical method investments made for del-brax carry direct relevance to the broader portfolio's CMC readiness.

The measurable outcome to watch is the Phase III primary endpoint readout, which will determine whether the KHDC1L and creatine kinase reductions seen in FORTITUDE translate into clinically meaningful functional outcomes under ICH E6(R3)-compliant trial conditions.

Source: Novartis via GlobeNewswire, 11 June 2026.