Sarepta Falls as Avidity's DMD Drug Data Signals Competition

Avidity Biosciences has reported promising results from its Phase I/II clinical trial for delpacibart zotadirsen (del-zota), a potential treatment for Duchenne muscular dystrophy (DMD). This news caused the company’s shares to rise by approximately 12% on Friday. Conversely, Sarepta Therapeutics, a market leader with four DMD therapies already available, experienced an 8% decline in its shares as investors considered the implications of increased competition.

Del-zota, also referred to as AOC 1044, uses phosphorodiamidate morpholino oligomers (PMOs) to target skeletal muscle and heart tissue. The treatment works by promoting exon 44 skipping in the dystrophin gene, which allows for the production of dystrophin in patients with DMD. The ongoing EXPLORE44 trial includes both ambulatory and non-ambulatory patients aged 7 to 27 years with DMD mutations that are amenable to exon 44 skipping (DMD44).

After a treatment period of four months at a dose of 5 mg/kg, del-zota showed a statistically significant 25% increase in dystrophin production compared to normal levels. Furthermore, the treatment restored total dystrophin to up to 54% of normal values. The drug also resulted in a notable 37% increase in exon 44 skipping, with some patients achieving up to 66% skipping. Additionally, creatine kinase levels, which indicate muscle damage, were reduced by more than 80% compared to baseline levels, bringing them close to normal. The treatment demonstrated favorable safety and tolerability, with most adverse events being mild or moderate in nature. The study is expected to conclude early next year.

"The robust exon skipping, significant dystrophin production, and profound reduction of creatine kinase reinforce our belief in the potential of del-zota to be an effective treatment for people living with DMD44," commented Sarah Boyce, CEO of Avidity Biosciences. "These data support expediting the regulatory path for del-zota as quickly as possible."

Avidity estimates that there are around 900 individuals in the United States with DMD44, a relatively smaller group compared to those with exon 45, 51, and 53 mutations targeted by Sarepta’s current treatments. Chardan analyst Keay Nakae highlighted that the EXPLORE44 trial does not measure the functionality improvements of del-zota, an area where Sarepta has faced challenges with its own drugs. However, Nakae believes that Avidity will likely explore this aspect in future studies.

"This data positions the company to continue evaluating additional DMD44 patients in order to accumulate sufficient patient experience that could support a possible accelerated approval," said Nakae.

Overall, the positive early results for del-zota offer hope for an effective treatment for DMD44 and signal a potential shift in the landscape of DMD therapies.