Trial Testing WVE-210201 in DMD Selected for FDA Pilot Program

The U.S. Food and Drug Administration (FDA) selected  Wave Life Sciences‘ Phase 2/3 trial assessing the efficacy and safety of WVE-210201 (suvodirsen) in Duchenne muscular dystrophy for its pilot program for complex innovative trial designs.

This initiative aims to modernize the design of clinical trials and advance drug development.

Wave will have additional opportunities to meet with FDA staff and discuss aspects of the trial’s design, such as the use of models and simulation that could lead to more efficient and productive conclusions.

Wave’s trial is among the first clinical protocols selected for the program, which was announced in August 2018. The FDA selected this trial because of its innovative design and the need for new therapies for Duchenne muscular dystrophy (DMD).

The innovative elements of the trial include a strategy to reduce the number of patients in the placebo arm; with this, Wave expects to reduce the time required to deliver conclusive results.

“In designing our clinical trials, we are constantly looking to maximize the probability of a definitive result, incorporate the feedback of patients and their families, and reduce the burden on those who are already bravely enduring the challenges associated with serious, genetically defined diseases. The FDA’s recognition of our plan reflects the thoughtful and collaborative way in which we approach clinical development,” Michael Panzara, MD, MPH, CEO of Wave Life Sciences, said in a press release.

“We look forward to further discussions with the FDA in the coming months and sharing learnings from our trial design with others in the rare disease drug development community to drive greater efficiency and productivity in future clinical studies.”

DMD is a genetic disease caused by mutations in the DMD gene, which contains the instructions to produce dystrophin, a protein involved in normal muscle function. DMD patients cannot produce functional dystrophin; this leads to chronic deterioration of the muscles.

WVE-210201 is an exon skipping therapy for people with DMD. The genes in our body are divided into small fractions called exons. WVE-210201 removes exon 51 from the DMD gene, thus producing a smaller, functional version of dystrophin.

The treatment is aimed at patients with mutations in the exon 51 (around 13% of all DMD patients). Pre-clinical studies in patient-derived muscle cells showed that WVE-210201 restored dystrophin activity to about half the normal levels.

A phase 1 clinical trial (NCT03508947) assessing the safety of WVE-210201 in boys ages 5-18 showed positive results.

These results provided the dose to be used and supported the design of the placebo-controlled Phase 2/3 efficacy and safety clinical trial. Wave plans to start the trial this year and expects that the results will lead to global approval for the therapy.

WVE-210201 is currently being tested in an ongoing open-label extension study. An interim analysis of dystrophin expression from this study is expected in the second half of 2019.

WVE-210201 was granted the FDA’s orphan drug and rare pediatric designations for the treatment of DMD, and orphan drug status from the European Commission.