Wave Begins Phase 1 Trial of Therapy That Addresses Exon Skipping in Duchenne MD

Wave Life Sciences has started a Phase 1 clinical trial of a treatment for a gene malfunction linked to the most common form of Duchenne muscular dystrophy.

Genes consists of dozens of components called exons. If an exon is missing, a gene can fail to produce a protein the body needs. Lack of the dystrophin gene’s exon 51 component is associated with the development of 13 percent of Duchenne MD cases. Scientists use the term exon skipping to refer to a break in the full exon sequence that a gene needs to work properly.

Wave Life Sciences’ therapy WVE-210201 addresses the exon 51 skipping that 13 percent of Duchenne MD patients have. The compound essentially prompts the gene to ignore the skipping.

The Phase 1 trial will look at the safety of different doses of WVE-210201 and patients’ ability to tolerate each. It will also look at plasma concentrations of the intravenous therapy — that is, how much of the compound is in a sample of blood plasma.

Wave has already begun the U.S. part of the global study, which will involve about 40 patients between 5-18 years of age.

“The initiation of WVE-210201’s clinical program is an important milestone in potentially delivering meaningful therapies for DMD patients,” Dr. Michael Panzara, head of Wave Life Sciences’ neurology program, said in a press release. “We are grateful to the DMD scientific and patient communities with whom we collaborated in designing our clinical program.”

Panzara added that Wave will continue its “close engagement with these key stakeholders as we advance candidates targeting other exons and explore additional innovative approaches to potentially treat DMD.”

Wave expects the Phase 1 trial results to be available in the third quarter of 2018. The next steps would likely be a trial and long-term extension study of the therapy’s effectiveness. The company thinks the initial effectiveness results will be available in 2019.

WVE-210201 is designed to restore the break in the gene sequence caused by exon 51 skipping. The restoration should lead to the production of a smaller, but functional dystrophin protein, Wave said.

Preclinical-trial studies have shown that WVE-210201 restores about 52 percent of the protein’s production.

“Wave’s stereopure chemistry platform has enabled the development of WVE-210201, which has shown substantially greater exon 51 skipping efficiency and dystrophin protein restoration” in preclinical-trial studies than other approaches, said Dr. Matthew Wood, a neuroscience professor at the University of Oxford. “These experimental results suggest the potential for meaningful benefits for DMD patients.”

“Parent Project Muscular Dystrophy is excited by the progress Wave Life Sciences has made in exon skipping,” said Pat Furlong, the organization’s founding president and CEO. “While advances have been made, there is more to explore within this technology.
“We appreciate the passion, partnership and understanding the Wave team has shown our Duchenne community,” he said. “We look forward to continued updates as Wave heads into its Phase 1 clinical trial.”