Novartis del-brax Phase I/II FSHD study meets primary biomarker endpoint

Novartis has announced that the biomarker cohort of its FORTITUDE Phase I/II study of delpacibart braxlosiran (del-brax) met both its primary and key secondary endpoints in patients with facioscapulohumeral muscular dystrophy (FSHD). The results add clinical weight to a Phase III programme already under way and reinforce the company's case for regulatory engagement ahead of a potential approval in an indication where no disease-modifying treatment currently exists.

The primary endpoint, a reduction in plasma KHDC1L (a circulating biomarker regulated by DUX4), was met alongside a reduction in creatine kinase, a marker of ongoing muscle damage. Cohort C enrolled 51 patients aged 16 to 70 on a 2 mg/kg dose given every six weeks over 12 months. Novartis said the safety profile was consistent with earlier dose-escalation cohorts presented at the FSHD International Research Congress in June 2025.

How del-brax works

Del-brax is an antibody oligonucleotide conjugate (AOC), a class of RNA therapeutic that pairs the tissue-targeting properties of monoclonal antibodies with small-interfering RNA to suppress DUX4 expression in muscle cells. FSHD is caused by aberrant activation of the DUX4 gene, which triggers a cascade of muscle-cell damage. Earlier approaches to silencing DUX4 struggled with delivery to muscle tissue, and the AOC format is positioned by Novartis as a solution to that problem.

Nazem Atassi, Global Head of Neuroscience and Gene Therapy Development at Novartis, said the Cohort C data "validate the dosing regimen implemented in our Phase III trial and lend further evidence of the potential for del-brax to have a significant impact for people with FSHD." He added that the company would engage global regulatory agencies with urgency.

Del-brax carries both FDA Orphan Drug and Fast Track designations and EMA Orphan Drug designation, which should support accelerated review processes if clinical data from Phase III prove out.

Competitive and market context

FSHD affects an estimated 45,000 to 87,000 people across the US and EU, making it a rare but commercially meaningful indication. Roughly one in five patients becomes wheelchair-dependent. The absence of any approved disease-modifying therapy means del-brax, if successful, would enter an effectively open market, a factor that contributed to Novartis paying to acquire Avidity Biosciences in February 2026, the deal through which del-brax entered the Novartis pipeline.

That acquisition also brought two further AOC candidates: del-desiran, in Phase III for myotonic dystrophy type 1 (DM1), and del-zota, in Phase II for Duchenne muscular dystrophy (DMD). Together, the three programmes give Novartis a breadth of rare neuromuscular coverage that few peers can match, extending its established franchise in spinal muscular atrophy. Competitors pursuing disease modification in FSHD at the clinical stage are limited, though several academic and smaller biotech groups are exploring gene-silencing approaches.

The pivotal FORTITUDE-3 Phase III study (NCT07038200) is currently enrolling 200 patients aged 16 to 70. Primary endpoints differ by region: quantitative muscle testing in the US and the 10-metre walk/run test in Europe, a split that reflects regulatory preference differences between the FDA and EMA for neuromuscular functional outcomes. Top-line data from FORTITUDE-3 will be the decisive readout for any approval bid, and investors will track enrolment pace and the timing of regulatory meetings closely over the next 12 to 18 months.