Paul Bolno, CEO, and Anne-Marie Li-Kwai-Cheung, Chief Development Officer, of Wave Life Sciences, discuss interim data from the ongoing FORWARD-53 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. Muscle weakness is usually noticeable in early childhood. DMD is caused by genetic changes in the DMD gene. Diagnosis of DMD is based on the symptoms, clinical exam, and the result of a biopsy to remove a small piece of muscle for examination under a microscope. The result of genetic testing may also help confirm the diagnosis. Becker muscular dystrophy (BMD), a milder form of muscular dystrophy, is also caused by genetic changes in the DMD gene.
WVE-N531 is an investigational exon skipping oligonucleotide therapy. It is currently being tested for treatment of boys with DMD that is susceptible to exon 53 skipping. The drug has received Orphan Drug Designation and Rare Pediatric Disease Designation from the U.S. Food and Drug Administration (FDA).
Clinial Trial
The FORWARD-53 clinical trial is a open-label, phase 2 study evaluating WVE-N531 for boys with DMD susceptible to exon 53 skipping. 11 boys are currently enrolled, receiving 10 mg/kg every two weeks. Primary endpoints include dystrophin expression after 24 and 48 weeks of treatment, pharmacokinetic, safety, and tolerability data, and functional assessments.
While final data from the trial is expected in the first quarter of 2025, interim results have been positive. After 24 weeks of treatment, substantial dystrophin expression, with a mean muscle content-adjusted dystrophin expression of 9%, has been observed. Additionally, WVE-N531 was detected in myocyte nuclei in all patients and in myogenic stem cells for the majority of patients. Researchers also observed improvements in muscle health and a reduction in creatine kinase and other serum biomarkers. The therapy has also shown positive safety and tolerability.
Following the final results of the study, the company hopes to pursue an accelerated approval pathway.
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To learn more about DMD and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/
