Brogidirsen

Avidity Biosciences shared Monday that its RNA drug for people with certain mutations of Duchenne muscular dystrophy continued to show strong results as it completed a Phase 1/2 study, and the biotech is planning to apply to the FDA for accelerated approval. The exon 44 skipping drug delpacibart zotadirsen, or del-zota for short, increased production of a shortened version of dystrophin by 25%. This is compared to a healthy control at four weeks after trial participants received their third dose. In August, the biotech already shared better-than-expected interim results on del-zota. It had been aiming for an increase in dystrophin production to about 10% above normal, but reported that del-zota led to a 25% increase. The key Phase 1/2 data reported Monday included seven participants who received the 5 mg/kg dose, 10 who got the 10 mg/kg dose, and six placebo participants. The 5 mg/kg was dosed every six weeks, while the 10 mg/kg was dosed every eight weeks. The San Diego-based biotech said it’s expecting to submit an application for accelerated approval to the FDA by the end of the year, and it’s hoping to launch the drug next year. Avidity is currently designing a confirmatory study, CEO Sarah Boyce said, and expects to share an update on those plans later this year. Avidity says it will be asking the FDA for approval for the lower 5 mg/kg regimen. The two doses “sit on top of each other at pretty much every measure, both from exon skipping, from dystrophin production, the changes in creatine kinase,” Boyce said. The data will be presented at the Muscular Dystrophy Association scientific meeting this week. Avidity also shared Monday that del-zota led to an increase of approximately 40% in exon 44 skipping. It also led to a reduction in levels of creatine kinase to “near normal,” the biotech said. Creatine kinase is an enzyme released from damaged muscle that’s elevated in people with Duchenne muscular dystrophy. “That’s not something that you see with gene therapy,” Boyce said in a Sunday interview with Endpoints News . “So we really see that for exon 44, del-zota really sets the standard for what can be achieved.” Avidity said the experimental drug has shown “​​favorable” safety across the Phase 1/2 study as well as an ongoing open-label extension trial. NS Pharma is also developing an exon 44 skipping drug, and an investigator-initiated study published in January showed that the 80 mg/kg dose of its drug brogidirsen led to an increase in dystrophin of 24.47% of normal at 24 weeks. Around 6% of people with Duchenne are amenable to exon 44 skipping. Del-zota and brogidirsen are part of a class of exon skipping drugs that are meant to make a shorter, but functional version of the muscle protein dystrophin by patching over the faulty section of the RNA encoding the protein. Unlike other exon skipping treatments, Avidity attached an antibody to its RNA drug to help deliver it to the muscle. Editor’s note: This story was corrected to reflect that dystrophin production was increased by 25% of normal. A previous version said to 25%.