Delpacibart Etedesiran

iStock, Deagreez 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. M&A Novartis To ‘Bolster’ Neuromuscular Pipeline With $12B Avidity Acquisition The deal, announced early Sunday afternoon, will see Novartis gain access to Avidity’s neuroscience assets, while the San Diego biotech spins out a new company to shepherd its early-stage precision cardiology programs. October 26, 2025 · 2 min read · Heather McKenzie Read more

Another RNA programme that Novartis pocketed from its $12-billion purchase of Avidity Biosciences has posted positive clinical findings. The pharma said Thursday that delpacibart braxlosiran (del-brax) met both its primary and key secondary endpoints in a mid-stage facioscapulohumeral muscular dystrophy (FSHD) study, supporting the dosage selected for an already-underway Phase III trial. The biomarker cohort of the Phase I/II FORTITUDE study assessed a 2-mg/kg dose of del-brax given every 6 weeks against placebo in 51 patients with FSHD between the ages of 16 and 70. The dose level was selected based on results from two earlier dose escalation cohorts, which were presented at last year's FSHD Society International Research Congress.Del-brax, an antibody oligonucleotide conjugate (AOC), is designed to deliver siRNA to suppress DUX4, a gene that is aberrantly expressed in the skeletal muscles of patients with FSHD. After 12 months, patients receiving del-brax saw lower plasma concentration levels of KHDC1L — a DUX4-regulated circulating biomarker — as well as reduced creatine kinase levels, which suggest successful target engagement and a reduction in muscle damage. According to Novartis, the AOC is the only experimental treatment with disease-modifying potential for FSHD."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," said Nazem Atassi, Novartis' global head of neuroscience and gene therapy development. "We are now evaluating the totality of the biomarker and clinical data and look forward to discussions with global regulatory agencies."Recruitment has already begun for the Phase III FORTITUDE-3 trial, which is aiming to enrol 200 patients with FSHD in the same age range as FORTITUDE. The study's primary endpoint will look at quantitative muscle testing in the US, and rely on the 10-meter walk/run test in Europe. Muscular dystrophy portfolioDel-brax is the latest Avidity programme to see clinical success. Through the biotech's buyout, Novartis also gained Duchenne muscular dystrophy (DMD) candidate delpacibart zotadirsen (del-zota), which impressed in the Phase I/II EXPLORE44 trial.The AOC delivers a phosphonodiamidite morpholino oligomer to muscle tissues, enabling dystrophin production in patients with DMD mutations amenable to exon 44 skipping. In EXPLORE44, del-zota increased dystrophin production to approximately 25% of normal levels in patients with DMD, with restored total dystrophin reaching up to 58% of normal (see – KOL Views Q&A: Novartis’ neuromuscular splash — Avidity’s del-zota may redefine DMD exon-skipping).The third asset Novartis acquired is delpacibart etedesiran, which is in the Phase III HARBOR study for myotonic dystrophy type 1.