Following its failure to increase dystrophin levels of patients in an early-stage clinical trial, Wave Life Sciences has discontinued development of the investigational exon-skipping therapy suvodirsen for people with Duchenne muscular dystrophy (DMD).
Lack of dystrophin, an essential protein for healthy muscles, causes DMD. Patients may carry disease-causing mutations in different exons, which are the tiny bits of DNA containing information needed to produce proteins.
Suvodirsen (previously known as WVE-210201) was designed to mask exon 51 in the messenger RNA produced from the DMD gene, to generate a shorter but working version of dystrophin. This means the therapy was intended for patients with mutations in that specific exon.
In a Wave-funded Phase 1 trial (NCT03508947), 36 DMD boys amenable to exon 51 skipping received varying doses of suvodirsen (0.5 mg/kg to 10 mg/kg, given intravenously) or a placebo, and were followed for 85 weeks. The therapy met the study’s primary goal of being safe and well-tolerated. Participants were allowed to continue in an open-label extension study, where they were given suvodirsen at 3.5 or 5 mg/kg, via weekly injections.
A new analysis of that extension study examined dystrophin levels in muscle biopsies taken from 27 boys either before or after 12 or 22 weeks of suvodirsen treatment.
Although no safety concerns were observed, results revealed that treatment with suvodirsen did not significantly increase dystrophin levels.
Based on this finding, Wave decided to stop development of suvodirsen. Participants will have a final follow-up visit, but no further doses will be given.
The decision includes the DYSTANCE 51 Phase 2/3 trial (NCT03907072). This study — the first ever selected by the U.S. Food and Drug Administration (FDA) for its complex innovative trial designs pilot program — was meant to assess suvodirsen’s safety and effectiveness, and was expected to support its global approval.
“We set out to restore meaningful levels of dystrophin in patients with Duchenne, and we failed to achieve this goal,” Michael Panzara, MD, Wave’s chief medical officer, said in a press release. “These results are not what we expected, particularly given the promising data from our preclinical models, and we commit to further analyzing and understanding the results to aid in future research.”
Panzara said the company will share additional results “so that the Duchenne community may benefit from its contributions to this study.”
Of note, suvodirsen recently had been granted fast track designation by the FDA as a possible therapy for people with DMD. Besides suvodirsen, Wave also is halting the development of WVE-N531 for patients with mutations in exon 53.
“The suvodirsen results are unexpected and deeply disappointing to us, and undoubtedly will be to the patients we aim to serve. … We will work to rapidly incorporate our learnings, so that we can seek to deliver on the promise of our current and future pipeline,” said Paul Bolno, MD, Wave’s CEO.
Wave hosted a conference call and live webcast to discuss this decision. To access a replay, visit this site.