Novartis reported positive Phase I/II FORTITUDE biomarker results for del-brax in facioscapulohumeral muscular dystrophy (FSHD), achieving primary and secondary endpoints, confirming target engagement, and supporting the Phase III dosing strategy.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Novartis reported positive results from the biomarker cohort of the Phase I/II FORTITUDE study, with its investigational therapy del-brax achieving both the primary and key secondary endpoints in patients with facioscapulohumeral muscular dystrophy (FSHD).
After 12 months of treatment, the therapy reduced KHDC1L, a transcriptional target of DUX4, and lowered creatine kinase, a marker of muscle damage. The safety profile remained consistent with previous studies, reinforcing confidence in the development program while confirming target engagement and downstream muscle protection.
Del-brax is among the most advanced investigational therapies for FSHD and has the potential to become the first disease-modifying treatment for the disease if ongoing studies confirm clinical benefit.
Addressing the Root Cause of FSHD
FSHD is one of the most common muscular dystrophies, driven by abnormal expression of the DUX4 gene. Symptoms typically emerge in adolescence or early adulthood, progressing to muscle weakness, pain, fatigue, and disability. Approximately 45,000–87,000 patients across the United States and Europe are estimated to be living with the disease, with about 20% eventually requiring a wheelchair.
Del-brax, an antibody oligonucleotide conjugate (AOC), combines monoclonal antibody targeting with siRNA technology to suppress DUX4 expression in skeletal muscle cells and address the underlying cause of FSHD. The therapy has received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration and Orphan Drug designation from the European Medicines Agency.
FORTITUDE Study Validates Dose Selection
The randomized, double-blind, placebo-controlled Phase I/II FORTITUDE study (NCT05747924) enrolled 90 patients with FSHD. Earlier dose-escalation cohorts evaluated del-brax at 2 mg/kg and 4 mg/kg, leading investigators to select 2 mg/kg every six weeks for further development.
Cohort C enrolled 51 patients aged 16–70 years and evaluated del-brax 2 mg/kg every six weeks versus placebo over 12 months.
The study met its primary endpoint of reducing plasma KHDC1L levels and its key secondary endpoint of lowering creatine kinase levels. These findings replicated the target engagement and muscle protection signals observed in earlier cohorts and validated the regimen now advancing in Phase III testing.
Regulatory Pathway and Phase III Development
Novartis plans to engage regulators on the totality of the Phase I/II data package while continuing enrollment in the global Phase III FORTITUDE-3 trial (NCT07038200). According to the company, the biomarker data support the dosing regimen selected for the pivotal study and further strengthen the evidence supporting del-brax’s disease-modifying potential.
The study is currently enrolling approximately 200 patients aged 16–70 years. Primary endpoints include quantitative muscle testing in the United States and the 10-meter walk/run test in Europe, functional measures intended to capture clinically meaningful benefit. Secondary endpoints assess patient-reported outcomes, functional performance, and biomarker changes.
Expanding Neuromuscular Portfolio
Del-brax entered the Novartis pipeline through the acquisition of Avidity Biosciences in February 2026. Alongside late-stage AOC-based programs in myotonic dystrophy type 1 and Duchenne muscular dystrophy, del-brax strengthens Novartis’ neuromuscular portfolio and underscores its strategy to advance disease-modifying therapies for rare genetic neuromuscular disorders.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.