Novartis del-brax meets primary endpoint in FSHD trial targeting 45k patients

Key Takeaways:

FORTITUDE Phase I/II met primary and key secondary biomarker endpoints
Del-brax reduced KHDC1L and creatine kinase levels in 51-patient cohort
Phase III enrolling 200 patients; Novartis to engage regulators on data

Novartis AG said Thursday its experimental therapy delpacibart braxlosiran (del-brax) met the primary and key secondary endpoints in the biomarker cohort of the FORTITUDE Phase I/II study, reducing KHDC1L and creatine kinase levels in patients with facioscapulohumeral muscular dystrophy.

"The FORTITUDE biomarker cohort data importantly replicate the target engagement and downstream muscle protection seen with del-brax in earlier dose-escalation cohorts," Nazem Atassi, global head of neuroscience and gene therapy development at Novartis, said in a statement. "These results 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."

The biomarker cohort, Cohort C, evaluated del-brax at 2 milligrams per kilogram every six weeks versus placebo for 12 months in 51 patients aged 16 to 70. The primary endpoint measured change in plasma concentration of KHDC1L, a DUX4-regulated circulating biomarker, while the key secondary endpoint tracked creatine kinase, a marker of muscle damage. The safety profile was consistent with earlier results from the two initial dose-escalation cohorts, which tested 2 mg/kg and 4 mg/kg doses.

FSHD is one of the most common forms of muscular dystrophy, affecting an estimated 45,000 to 87,000 people in the US and European Union. Caused by aberrant expression of the DUX4 gene, the disease typically emerges in teenage or early adult years and leads to progressive muscle weakness, pain and disability, with about 20 percent of patients becoming wheelchair dependent. No approved therapies currently exist.

Del-brax combines monoclonal antibody tissue specificity with oligonucleotide precision to deliver siRNA that suppresses DUX4 expression in muscle cells. The therapy has received FDA Orphan Drug and Fast Track designations as well as EMA Orphan Drug designation. Novartis acquired the drug through its purchase of Avidity Biosciences in February 2026, a deal that also added delpacibart-etedesiran (del-desiran) in Phase III for myotonic dystrophy type 1 and delpacibart-zotadirsen (del-zota) in Phase II for Duchenne muscular dystrophy.

The Phase III FORTITUDE-3 study (NCT07038200) is currently enrolling 200 patients with FSHD aged 16 to 70. The primary endpoint is quantitative muscle testing in the US and the 10-meter walk or run test in Europe, with secondary endpoints including additional functional measures and patient-reported outcomes. Novartis plans to engage global regulatory authorities on the Phase I/II data.

The positive readout positions del-brax as the only investigational agent showing disease-modifying potential for FSHD in clinical studies. Success in the ongoing Phase III trial and subsequent regulatory approval would give Novartis a first-in-class therapy in a neuromuscular market where the company already holds a strong position through its spinal muscular atrophy franchise. Investors will watch for regulatory filing timelines after discussions with global health authorities.

This article is for informational purposes only and does not constitute investment advice.