Novartis gets win for another Avidity muscular dystrophy AOC
Armed with new clinical data, Novartis is planning to talk to global regulators about possible filings for delpacibart braxlosiran (del-brax), which could become the first disease-modifying treatment for facioscapulohumeral muscular dystrophy (FSHD).
In the phase 1/2 FORTITUDE study, intravenous administration of antibody oligonucleotide conjugate (AOC) del-brax showed significant reductions in biomarkers for muscle damage in the muscle-wasting disorder, including KHDC1L (cDUX) and creatine kinase, with a safety profile that Novartis said supported further development.
There was also less decline in movement and muscle strength than was observed in patients who received a matched placebo.
The Swiss pharma group – which acquired rights to del-brax as part of its $12 billion takeover of RNA specialist Avidity Biosciences earlier this year – said it is already enrolling patients in the phase 3 FORTITUDE-3 trial. Potentially at least, that might serve as a confirmatory study, if regulators are prepared to consider accelerated approval based on biomarker results.
Another Avidity-sourced AOC – exon 44-skipping candidate delpacibart zotadirsen (del-zota) – has already hit the mark in clinical trials as a treatment for Duchenne muscular dystrophy (DMD), which Avidity said last year was being prepared for regulatory filings in early 2026. A third, delpacibart etedesiran (del-desiran) is in clinical development for myotonic dystrophy type 1 (DM1), another neuromuscular disorder.
In people with FSHD, a gene called DUX4 is erroneously switched on, leading to the build-up of a harmful protein, DUX4, which is responsible for the muscle damage and weakness that characterise the disease. It is the second most common form of muscular dystrophy after DMD, affecting somewhere between 45,000 and 87,000 people in the US and EU, and has no approved treatments.
KHDC1L levels increase when DUX4 is active, so the reduced levels seen with del-brax treatment suggest that the AOC is curtailing the effects of DUX4 in the body.
"The FORTITUDE biomarker cohort data importantly 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.
"We are now evaluating the totality of the biomarker and clinical data and look forward to discussions with global regulatory agencies as we work with urgency to advance the development of del-brax for patients in need."
When it completed the Avidity takeover in February, Novartis said that the biotech's AOC pipeline has the potential to unlock "multi-billion-dollar opportunities with planned product launches before 2030."
