Novartis announced on June 12 that its $12 billion acquisition of Avidity Biosciences is showing early promise, with new data from a Phase 1/2 study of an investigational RNA medicine for facioscapulohumeral muscular dystrophy. The company reported promising biomarker findings for delpacibart braxlosiran, also known as del-brax, in patients enrolled in the FORTITUDE trial.
The FORTITUDE study included 90 patients who received either del-brax or a placebo. The primary outcome was the treatment effect on KHDC1L, a plasma disease biomarker for facioscapulohumeral muscular dystrophy (FSHD). Novartis said that the biomarker cohort met its primary and key secondary endpoints but did not disclose specific data. According to the company’s news release, KHDC1L levels were reduced in patients treated with del-brax, suggesting strong target engagement.
Del-brax also led to lower creatine kinase concentrations among treated patients. Novartis said this reduction indicates less muscle damage compared to those receiving placebo. "These findings 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 prepared statement.
A previous readout from FORTITUDE showed that patients on del-brax improved on several physical function tests at 12 months compared to placebo controls. These included better performance on the 10-meter walk-run test and timed up-and-go test as well as quantitative assessments of muscle and upper limb function.
Atassi said Thursday that Novartis is evaluating all available biomarker and clinical data, and plans further discussions with global regulatory agencies about next steps for approval. Meanwhile, Novartis has launched a Phase 3 trial called FORTITUDE-3 to enroll around 200 patients and assess effects on muscle performance.
Facioscapulohumeral muscular dystrophy is a rare neuromuscular disease affecting between 45,000 and 87,000 people across the United States and Europe. It is caused by abnormal expression of the DUX4 protein, leading to progressive muscle wasting. Del-brax targets this mechanism by combining antibodies with oligonucleotides designed to suppress DUX4 expression.
