After some earlier data sparked questions from analysts, Avidity Biosciences has released more data for its RNA-based Duchenne muscular dystrophy (DMD) candidate.
In a phase 1/2 trial, most adverse events after treatment with the antibody oligonucleotide conjugate, called delpacibart zotadirsen (del-zota), were mild to moderate, Avidity said in a March 17 release.
Prior del-zota data prompted concern from analysts due to occurrences of anaphylaxis and an infusion-related reaction, which led to two patients dropping out of the trial.
Since those earlier discontinuations, no other patients have dropped out of the trial due to an adverse event, Avidity said in a March 17 presentation. The most common side effects for patients given del-zota were procedural pain and headache.
“Safety is clean,” analysts from Evercore ISI wrote after the company's update March 17. “This update assuaged that potential concern” of anaphylaxis and infusion-related reactions.
The new data are from patients with DMD who received either 5 milligrams or 10 milligrams of del-zota per kilogram of body weight, with results consistent across doses. Past data released in August 2024 were limited to patients given 5 milligrams of the drug per kilogram of body weight.
Treatment with the antibody oligonucleotide conjugate increased dystrophin production by 25%, the San Diego biotech shared in August, which restored total dystrophin levels by 58%. The treatment also reduced creatine kinase, a marker of muscle damage, by as much as 80% from baseline.
The phase 1/2 trial, dubbed Explore44, wrapped up in November 2024 and studied the effect of del-zota in healthy volunteers and patients with DMD amenable to exon 44 skipping.
An open-label extension of the trial is currently underway. The latest safety data came from 38 patients in the extended portion of the trial and 26 from the completed portion.
Evercore analysts found the reduction in creatine kinase, a key biomarker of DMD, “very intriguing,” they wrote. “We hope this is a harbinger of functional benefit.”
Avidity plans to present data on functional benefit in the fourth quarter of 2025, according to the release.
Further, the company plans to submit a biologics license application for del-zota at the end of the year. The asset has received rare pediatric disease and fast track designations from the FDA as well as an orphan drug designation from both the FDA and the European Medicines Agency, according to the release.
Because the 10-milligram results were similar to past 5-milligram results, Avidity has determined it will use dosing of 5 milligrams per kilogram of body weight every six weeks as it moves forward into future clinical trials.