Aravindhan Veerapandiyan, MD, Assistant Professor of Pediatrics, University of Arkansas and Arkansas Children’s Hospital, discusses results from the phase 1/2 EXPLORE44 clinical trial for Duchenne muscular dystrophy (DMD).
DMD affects the muscles, leading to progressive muscle wasting. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and atrophy of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, or walk and difficulties learning to speak. DMD is caused by genetic changes in the Dystrophin gene.
Del-zota is a part of a new class of RNA therapeutics called antibody oligonucleotide conjugates (AOCs). It is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal and cardiac muscle tissues. This targets the skipping of exon 44 of the dystrophin gene and enables production of near-full length dystrophin.
EXPLORE44 Clinical Trial
The phase 1/2 EXPLORE44 clinical trial is a randomized, double-blind, placebo-controlled, study evaluating the efficacy, safety, and tolerability of del-zota in two dose levels of 5 mg/kg and 10 mg/kg.
From the recent data, targeted delivery of PMOs resulting in approximately 200nM tissue concentrations in skeletal muscle were observed. There was also a statistically significant increase of about 40% in exon 44 skipping, and an increase of about 25% of normal dystrophin production and restored total dystrophin up to 58% of normal. Additionally, a reduction in creatine kinase levels to near normal with greater than 80% reductions compared to baseline were observed.
Additionally, patients originally treated with placebo demonstrated a reduction of creatine kinase levels to near normal upon treatment with del-zota. Significant reductions were also seen in the EXPLORE 44 open label expansion with continued treatment up to one year.
Finally, del-zota illustrated a favorable safety and tolerability profile with the majority of treatment emergent adverse events being mild or moderate. The results from this study were consistent in all parameters for both the 5 mg/kg and 10 mg/kg groups.
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For more information on DMD and other rare musculoskeletal disorders, visit https://checkrare.com/diseases/musculoskeletal-diseases/