Wave Life Sciences Receives FDA Rare Pediatric Disease Designation for the Treatment of Duchenne Muscular Dystrophy

Wave Life Sciences Ltd. recently announced the US FDA has granted Rare Pediatric Disease Designation to WVE-N531 for the treatment of boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping. WVE-N531 is currently being evaluated in the potentially registrational FORWARD-53 clinical trial and Wave expects to deliver data, including dystrophin protein expression from muscle biopsies after 24 weeks of treatment, in the third quarter of 2024.

“This designation from FDA underscores that significant unmet needs remain in DMD, and it also supports Wave’s innovative and purposeful approach to drug development in the rare disease space,” said Anne-Marie Li-Kwai-Cheung, MChem, MTOPRA, RAPS, Chief Development Officer at Wave Life Sciences. “With our WVE-N531 program, we are aiming to restore clinically meaningful levels of near full length, functional dystrophin protein. Positive data from FORWARD-53 would also unlock additional programs for other exons in our pipeline, with the goal of developing best-in-class medicines that address the underlying cause of the disease for up to 40% of boys with DMD.”

WVE-N531 is an exon skipping oligonucleotide designed to induce production of endogenous, functional dystrophin protein. In the previously completed Part A study (three 10 mg/kg doses every other week), WVE-N531 achieved industry-leading mean exon skipping levels of 53% and mean muscle tissue concentrations of ~42,000 ng/g (~6,100 nM), which is approximately 20-30 times higher than levels reported by exon-skipping technologies leveraging muscle delivery conjugates in DMD patients. The Part A data also demonstrated distribution to myogenic stem cells (also known as satellite cells) in all study participants. Myogenic stem cells are progenitor cells for new myoblasts, and Wave is not aware of any other clinical data for exon skipping therapies or gene therapies that have demonstrated myogenic stem cell uptake. Preclinical data in non-human primates also demonstrated concentrations of WVE-N531 in the heart and diaphragm that exceeded skeletal muscle, which indicates the potential for WVE-N531 to also offer cardiac and respiratory benefits.

WVE-N531 is currently being investigated in FORWARD-53, a potentially registrational, open-label clinical trial in 11 boys with DMD. Endpoints include dystrophin expression after 24 and 48 weeks of treatment, as well as pharmacokinetic, safety and tolerability data.

Rare Pediatric Disease Designation is granted by the FDA for serious or life-threatening diseases which primarily affect individuals less than 18 years of age and fewer than 200,000 people in the US. If a New Drug Application for WVE-N531 is approved by the FDA, Wave would be eligible to receive a Priority Review Voucher.

Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic neuromuscular disorder caused predominantly by out-of-frame deletions in the dystrophin gene, resulting in absent or defective dystrophin protein. Dystrophin protein is needed for normal muscle maintenance and operation. Because of the genetic mutations in DMD, the body cannot produce functional dystrophin, which results in progressive and irreversible loss of muscle function, including the heart and lungs. Worldwide, DMD affects approximately one in 5,000 newborn boys. Approximately 8%-10% of DMD patients have mutations amenable to treatment with an exon 53 skipping therapy. Exon skipping aims to address the underlying cause of DMD by promoting the production of dystrophin protein to stabilize or slow disease progression.

Wave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders. Its toolkit of RNA-targeting modalities includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency and Huntington’s disease, as well as a preclinical program in obesity. Driven by the calling to “Reimagine Possible”, Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information, visit www.wavelifesciences.com.