Avidity Biosciences anticipates to provide new cohort data from the phase 1/2 EXPLORE44 trial assessing AOC 1044 in Duchenne muscular dystrophy mutations amenable to exon 44 skipping in the second half of 2024.
According to a recent announcement, the FDA has granted rare pediatric disease designation to AOC 1044, Avidity Biosciences’ investigational therapy for the treatment of Duchenne muscular dystrophy (DMD) in patients living with mutations amenable to exon 44 skipping (DMD44).1 The company noted that it is expected to share 5 mg/kg cohort data from the phase 1/2 EXPLORE44 trial (NCT05670730) assessing the therapy in patients with DMD44 in the second half of 2024.2
EXPLORE44 is a randomized, placebo-controlled, double-blind trial comprised of healthy volunteers and patients with DMD44. In December 2023, the company announced topline data from the trial that showed AOC 1044 was safe among healthy volunteers and delivered 50-times greater concentrations of phosphorodiamidate morpholino oligomers (PMO) in skeletal muscle following administration. AOC 1044, a proprietary monoclonal antibody, binds the transferrin receptor 1 conjugated with a PMO targeting exon 44.
"We are pleased that the FDA has granted rare pediatric disease designation to AOC 1044, adding to the orphan drug and fast track designations already granted. The effects of DMD44 are devastating, with symptoms often starting in childhood. These designations by the FDA underscore the urgent need for innovative treatments and validate the potential of AOC 1044 to address the unmet need of patients living with Duchenne muscular dystrophy,"
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In a cohort of approximately 40 healthy volunteers, AOC 1044 delivered unprecedented, dose-dependent increases in PMO concentrations in skeletal muscle following a single dose of 5 mg/kg or 10 mg/kg, which were significantly greater when compared with a single dose of peptide conjugated PMOs. At day 29, patients treated with a single dose of 10 mg AOC 1044 demonstrated statistically significant exon 44 skipping of up to 1.5% in comparison with placebo. The investigational therapy was well tolerated in healthy volunteers, with all treatment-emergent adverse events (TEAEs) considered mild to moderate. There were no reports of symptomatic hemoglobin changes, no hypomagnesemia, and no renal events.
"We recently shared healthy volunteer data of AOC 1044 from our phase 1/2 EXPLORE44 trial demonstrating unprecedented delivery of therapeutic oligonucleotide in skeletal muscle and consistent exon skipping in healthy volunteers, and we look forward to sharing data from that study in patients living with DMD44 later this year. We remain steadfast in our commitment to advancing science and improving the lives of people and their families affected by this devastating condition,” Hughes said in a statement.1
In August 2023, the
DMD is a condition is driven by a genetic mutation, preventing the body from the production of the dystrophin protein. Therefore, the lack of functional dystrophin can lead to stress and tears of muscle cell membranes, which then ultimately results in muscle cell death, inflammation, and progressive loss of muscle function. Hence, AOC 1044 aims to deliver PMOs to skeletal muscle and heart tissue, causing exon 44 of the dystrophin gene to be skipped and enabling the production of functional dystrophin protein.
In another
"We are pleased that the FDA has granted breakthrough therapy designation to del-desiran for DM1, underscoring the potential of del-desiran to be an effective treatment and the urgency of bringing this treatment to patients living with DM1," Sarah Boyce, president and chief executive officer at Avidity, said in a statement.4 "Initiation is underway for our global phase 3 HARBOR study as we focus on rapidly advancing del-desiran for patients living with DM1, who currently have no treatment options to address the underlying cause of this devastating rare muscle disease."
In March 2024, the company announced
HARBOR is expected to include the same key end points as MARINA, with change in video hand opening time as the primary end point, along with secondary outcomes of muscle strength and activities of daily living. The trial, spanning more than 40 global sites, will randomly assign 150 patients to either AOC 1001 4 mg/kg or placebo every 8 weeks for a 54-week treatment period, followed by an OLE. Of note, the primary analysis is expected to cover the first 30 weeks of the study.
