Wave Life Sciences has shared their promising new interim results for the ongoing FORWARD-53 trial. The ongoing open-label trial, involves eleven boys amenable to exon 53 skipping (age 5-11; 10 ambulatory and 1 non-ambulatory). The study is designed to administer 10 mg/kg infusions of WVE-N531, with muscle biopsies being taken after 24 and 48 weeks of dosing.
Summary of Interim Findings:
- Mean muscle content-adjusted dystrophin expression of 9.0% and unadjusted dystrophin of 5.5%, with high consistency across participants, in a prespecified analysis; dystrophin was comprised of two isoforms consistent with Becker muscular dystrophy patients who display milder disease
- Data demonstrated meaningful improvement in serum biomarkers for muscle health, with localization of WVE-N531 in myogenic stem cells and regeneration of myofibers
- Skeletal muscle concentrations of ~41,000 ng/g combined with 61-day tissue half-life support monthly dosing going forward; preclinical data suggest participants may have even higher concentrations in heart and diaphragm
- WVE-N531 was safe and well tolerated: treatment-related adverse events were all mild, no serious adverse events, no discontinuations and no oligonucleotide class-related events
- Wave expects feedback on a pathway to accelerated approval from regulators, as well as the complete 48-week FORWARD-53 data, in 1Q 2025
We have long believed that our novel platform chemistry offered an opportunity to reimagine therapeutics for Duchenne, and we are looking forward to sharing further updates on WVE-N531
Paul Bolno, MD, MBA, President and CEO of Wave Life Sciences
The early results suggest the treatment is safe, with only four adverse events (three patients) reported to be mild in intensity. There were no serious adverse events and no study discontinuations due to any causes. In addition, there were no reported oligonucleotide class-related safety events.
The promising results suggest an effective exon skipping treatment (average 57% exon skipping – measured using RT-PCR), with good dystrophin expression at this interim stage of the trial. We look forward to seeing the results as the trial progresses, and latterly with the potential inclusion of functional measures to determine the translation of these results.
What is WVE-N531?
WVE-N531 is a novel exon skipping oligonucleotide designed to modify the disease course in boys with Duchenne muscular dystrophy who are amenable to exon 53 skipping.
Leveraging Wave’s proprietary oligonucleotide chemistry, including PN backbone modifications, WVE-N531 is designed to effectively restore a partially functional dystrophin protein by skipping exon 53.
Currently, WVE-N531 is being evaluated in the ongoing Phase 2 FORWARD-53 clinical trial, with additional data anticipated in the first quarter of 2025.
WVE-N531 has been granted Orphan Drug Designation and Rare Paediatric Disease Designation by the U.S. Food and Drug Administration, reflecting its potential to address a significant unmet medical need in this patient population
Would you like to know more about Duchenne muscular dystrophy? Increase your knowledge and understanding of Duchenne with our bite-sized science video series.
Section 1 – Facts about Duchenne muscular dystrophy
Section 2 – Signs and Symptoms of Duchenne muscular dystrophy
Section 3 – Diagnosis of Duchenne muscular dystrophy
Section 4 – Crucial Genetic Terminology
Section 5 – Genetics – Blueprint of Duchenne muscular dystrophy
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