Novartis has reported positive topline results from the Phase 1/2 FORTITUDE study of delpacibart braxlosiran (del-brax), an investigational RNA-based therapy for facioscapulohumeral muscular dystrophy (FSHD). The company said it plans to discuss the data with global regulatory agencies as it considers the next steps for the treatment’s development.
The results come from del-brax, one of the assets Novartis obtained through its $12 billion acquisition of Avidity Biosciences, which closed in February after being announced in October of the previous year. The company has already initiated a Phase 3 trial of the therapy while evaluating the full set of findings from the Phase 1/2 study.
The FORTITUDE study enrolled 90 patients who received either del-brax or placebo. The trial’s primary outcome included the effect of treatment on KHDC1L, a plasma biomarker associated with FSHD. According to Novartis, the biomarker cohort, which included 51 participants, achieved both its primary endpoint and key secondary endpoints.
The company reported that treatment with del-brax reduced levels of KHDC1L, a circulating biomarker regulated by DUX4. KHDC1L is used as a plasma disease biomarker in FSHD, and Novartis said the reduction observed in the study suggests strong target engagement. In FSHD, abnormal expression of DUX4 leads to changes in gene expression associated with progressive loss of muscle function. The DUX4 protein also activates genes that are toxic to muscle tissue.
Investigators also observed a decrease in creatine kinase levels among treated patients. Novartis stated that the reduction is indicative of reduced muscle damage in treated patients. The company reported declines in both KHDC1L and creatine kinase, findings that it said were consistent with the intended biological activity of the therapy.
“These findings replicate the target engagement and downstream muscle protection seen with del-brax in earlier dose-escalation cohorts,” said Nazem Atassi, global head of neuroscience and gene therapy development at Novartis.
Del-brax is an antibody-oligonucleotide conjugate that combines a small interfering RNA designed to target DUX4 messenger RNA with an anti-TfR1 antibody. The antibody component is intended to deliver the therapeutic payload to muscle cells, where it can suppress DUX4 expression and address the underlying disease mechanism. According to the information provided, the therapy combines the specificity of antibodies with the precision of oligonucleotides to target and suppress DUX4 expression.
Earlier FORTITUDE data from dose-escalation cohorts showed improvements in several functional measures after 12 months of treatment. Patients receiving del-brax performed better than placebo recipients on the 10-meter walk-run test, the timed up-and-go assessment, and quantitative measures of muscle and upper-limb function, while placebo-treated participants deteriorated.
Novartis said it is evaluating the totality of the biomarker and clinical findings and plans to engage with regulatory agencies worldwide. Earlier this year, Chief Executive Officer Vas Narasimhan said the company intended to discuss the possibility of accelerated approval with the U.S. Food and Drug Administration based on Phase 1/2 data.
Meanwhile, the Phase 3 FORTITUDE-3 study is underway and is expected to enroll approximately 200 patients. The trial is designed to evaluate the effects of del-brax on muscle strength, muscle performance, and other clinical outcomes through Week 78.
Del-brax was one of three RNA-based therapies acquired through the Avidity transaction, alongside del-zota for Duchenne muscular dystrophy and del-desiran for myotonic dystrophy type 1, as well as several preclinical neuromuscular disease programs.
Novartis has reported positive Phase 1/2 clinical trial results for Del-Brax, providing new hope for patients living with facioscapulohumeral muscular dystrophy (FSHD). The encouraging findings mark an important milestone for Novartis as the company continues to expand its presence in rare and underserved disease areas.
Novartis Shares Positive Del-Brax Clinical Data
The latest study results indicate that Novartis achieved key objectives related to safety, tolerability, and early signs of therapeutic activity. These findings support the continued development of Del-Brax and reinforce confidence in the treatment’s potential to address the underlying causes of FSHD.
Novartis Advances Treatment Options for FSHD
FSHD is a progressive genetic muscle disorder that currently has limited treatment options. Through the development of Del-Brax, Novartis aims to address a significant unmet medical need and improve outcomes for individuals affected by this challenging condition.
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