Forty-five thousand to 87,000 people in the US and EU live with facioscapulohumeral muscular dystrophy, and for decades the disease has been managed without a single approved therapy that touches its underlying biology. That context makes the FORTITUDE Cohort C data genuinely consequential: Novartis reported this week that del-brax, its investigational antibody oligonucleotide conjugate, met both the primary and key secondary endpoints of its Phase I/II biomarker cohort, reducing plasma KHDC1L levels and creatine kinase concentrations in 51 patients treated over 12 months.
The two endpoints tell a layered story. KHDC1L is a DUX4-regulated circulating protein, identified through mass spectrometry on DUX4-inducible human myoblasts and now validated as a direct read on target engagement. Creatine kinase reduction sits downstream, indicating actual muscle protection rather than just pathway suppression. Together, these results from Cohort C replicate what earlier dose-escalation cohorts A and B showed at the 32nd FSHD International Research Congress in June 2025, and they lock in the 2 mg/kg every-six-weeks regimen already running in the Phase III study, FORTITUDE-3, which is currently enrolling 200 patients aged 16 to 70.
The Phase III design splits its primary endpoint by geography: quantitative muscle testing in the US, the 10-meter walk/run test in Europe. That dual-primary structure carries real regulatory risk, because the two instruments measure related but distinct functional constructs, and a divergent outcome between regions would complicate a unified approval narrative. Novartis says it will engage global regulatory authorities on the Phase I/II data before Phase III readout, which suggests the company is testing whether an accelerated or conditional pathway is possible on biomarker grounds. The del-brax program is one of three AOC assets Novartis absorbed through its $12 billion acquisition of Avidity Biosciences completed in February 2026, alongside del-desiran in Phase III for myotonic dystrophy type 1 and del-zota in Phase II for Duchenne muscular dystrophyDuchenne muscular dystrophy.
The number to watch now is how quickly FORTITUDE-3 completes enrollment. With regulatory conversations beginning on Phase I/II data and a Phase III already running, the critical question is whether those agency discussions produce any expedited designation or surrogate-endpoint agreement that shortens the path to a confirmatory readout. KHDC1L’s acceptance as a reasonably likely surrogate would be the single event that most accelerates del-brax’s timeline and validates the entire AOC platform’s clinical credibility.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
