The RNA-based medicine is one of a handful of antibody-oligonucleotide conjugates that Novartis acquired last October when it took over neuromuscular-focused Avidity Biosciences.
Novartis’ $12 billion gambit for Avidity Biosciences late last year is starting to pay off, with the pharma reporting promising biomarker findings for its investigational RNA medicine in patients with facioscapulohumeral muscular dystrophy.
In the Phase 1/2 FORTITUDE study, Novartis enrolled 90 patients to receive the antibody-oligonucleotide conjugate delpacibart braxlosiran (del-bax) or placebo. Aside from safety, the trial’s primary outcome is the treatment effect on KHDC1L, a plasma disease biomarker for facioscapulohumeral muscular dystrophy (FSHD).
Without disclosing specific data, Novartis in a Thursday news release said that FORTITUDE’s biomarker cohort met its primary and key secondary endpoints. KHDC1L levels were reduced in patients treated with del-brax, suggesting “strong target engagement,” the pharma noted.
Del-brax also elicited a drop in creatine kinase concentrations, which Novartis explained is indicative of “reduction in muscle damage” in treated patients.
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 FORTITUDE readout covering earlier dosing cohorts showed that patients on del-brax improved on the 10-meter walk-run test at 12 months compared to placebo. Similarly, those given del-brax performed better on the timed up-and-go test as well as on quantitative muscle and upper limb function assessments at 12 months while placebo controls deteriorated.
“We are now evaluating the totality of the biomarker and clinical data and look forward to discussions with global regulatory agencies,” Atassi said on Thursday, though Novartis hasn’t yet specified filing plans for the asset. The pharma, meanwhile, has launched the Phase 3 FORTITUDE-3 trial of del-brax in FSHD, aiming to enroll around 200 patients and looking at the therapy’s effects on muscle performance.
FSHD is a rare and progressive neuromuscular disease that manifests as a life-long muscle wasting, pain, fatigue and disability. The condition, affecting some 45,000 to 87,000 people across the U.S. and Europe, is caused by the abnormal expression of the DUX4 protein, which in turn activates genes that are toxic to muscles. Del-brax addresses this disease mechanism by combining the specificity of antibodies and the precision of oligonucleotides to target and suppress the expression of DUX4, according to Avidity’s website.
The asset came to Novartis through the pharma’s $12 billion takeover of Avidity in October last year, alongside two other RNA-based therapies: del-zota, being proposed for Duchenne muscular dystrophy, and del-desiran, being trialed for myotonic dystrophy type 1. The pharma also won over a clutch of preclinical programs for other rare neuromuscular disorders.
Novartis closed the Avidity acquisition in February.
