The Duchenne muscular dystrophy community received some rare good news on Friday when Avidity Biosciences reported surprisingly positive clinical results in DMD and plans to advance its RNA therapy.
The San Diego biotech shared early Phase 1/2 data showing its RNA drug produced a 25% increase in the production of dystrophin, a protein required for muscle function that DMD patients lack. The drug, previously called AOC 1044, has been renamed delpacibart zotadirsen, or del-zota for short.
Avidity CEO Sarah Boyce said her company now plans to discuss with the FDA the “fastest route to an accelerated approval” for del-zota while carrying on with research on additional antisense oligonucleotide drugs to reach more DMD patients.
“We’re now committed to full steam ahead with our DMD franchise,” Boyce said Friday morning during an investor call.
Avidity’s pipeline lists preclinical work targeting exon 45 and other undisclosed DMD targets.
Its stock $RNA opened up about 13% on Friday morning, continuing an exceptional run for the $4.7 billion drugmaker that has seen its stock price increase more than 360% year-to-date. The company is developing a new class of drugs it calls antibody oligonucleotide conjugates and has previously reported study successes in other rare muscle diseases.
In a Friday note to investors, Leerink Partners analyst Joseph Schwartz said the early Avidity data exceeded investor expectations. He had previously estimated the drug could get patients to 7% to 13% of normal dystrophin expression. Instead, Avidity’s data increased DMD patients to 32% of healthy dystrophin levels.
Del-zota targets a sliver of DMD patients with mutations in exon 44, a specific part of the DMD gene. Avidity estimates there are about 900 people in the US in this subgroup, out of a DMD population in the US of about 10,000 to 15,000 people, predominantly boys.
The results are still early. Avidity only reported data for its low dose of 5 mg/kg. The study, called EXPLORE44, is also testing a 10 mg/kg dose. The company’s leaders said Friday that they changed the study’s plans based on the positive early results and are no longer planning to go up to 20 mg/kg.
The dose-escalating study was designed to primarily study safety and tolerability. Two of the nine patients treated with Avidity’s low dose left the study due to adverse events, Avidity reported. One patient had a “moderate infusion-related reaction,” while another discontinued due to serious anaphylaxis.
Avidity’s clinical success comes as some prominent late-stage DMD programs have disappointed in the clinic. In June, Pfizer’s DMD gene therapy failed a Phase 3 study, subsequently leading to the program’s end, a $230 million impairment charge, and layoffs at a North Carolina facility involved in the project.
Last year, Sarepta Therapeutics and Roche reported their DMD gene therapy Elevidys failed to hit a confirmatory study’s primary endpoint. Despite the setback, the FDA controversially awarded the drug a full and expanded approval, reflecting the need for treatment options for the devastating muscle disease.