EXPLORE44's Approach to Rare Disease Treatment for Duchenne Muscular Dystrophy: Steve Hughes, MD

WATCH TIME: 4 minutes

"For all rare diseases, there is a high unmet need from the patients because historically there hasn't been a big focus on rare diseases. So, the regulators have put in place mechanisms, such as orphan drug designation, in order to encourage companies to focus on rare diseases, as well as other diseases. We're focused on rare diseases and as a company, we're focused on rare diseases that don't have a lot of treatment options available.”

In patients living with Duchenne muscular dystrophy (DMD), a rare neurologic disease, the condition is driven by a genetic mutation and prevents the body from producing dystrophin protein. Thus, not having enough functional dystrophin can lead to stress and tears of muscle cell membranes, ultimately resulting in muscle cell death, inflammation, and progressive loss of muscle function. In recent news, the FDA granted orphan drug designation to Avidity Biosciences’ AOC 1044, an investigational treatment for DMD in patients with mutations amenable to exon 44 skipping (DMD44).¹

The therapy is being assessed in the phase 1/2 EXPLORE44 trial (NCT05670730), evaluating AOC 1044 in healthy volunteers and patients with DMD44. The trial plans to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of the therapy, administered intravenously. EXPLORE44 will primarily focus on exon skipping and dystrophin protein levels in treated patients, who will have the option to enroll into an extension study upon completion of the double-blind period.

Recently, Steve Hughes, MD, chief medical officer at Avidity, sat down in an interview with NeurologyLive® to discuss how the EXPLORE44 trial addresses the challenges associated with rare disease treatments, specifically with DMD. He also talked about the significance of FDA orphan drug designation and fast track status for the development of treatments for rare diseases, in particular with AOC 1044. In addition, Hughes elaborated on the 2 phases of EXPLORE44 and how they both will contribute to its potential success.

REFERENCES
1. Avidity Biosciences Receives FDA Orphan Drug Designation for AOC 1044 for Treatment of Duchenne Muscular Dystrophy in People with Mutations Amenable to Exon 44 Skipping. News Release. Avidity Biosciences. Published August 15, 2023. Accessed August 28, 2023 . https://aviditybiosciences.investorroom.com/2023-08-15-Avidity-Biosciences-Receives-FDA-Orphan-Drug-Designation-for-AOC-1044-for-Treatment-of-Duchenne-Muscular-Dystrophy-in-People-with-Mutations-Amenable-to-Exon-44-Skipping