Michael Panzara, MD, MPHMichael Panzara, MD, MPH
The FDA has granted Wave Life Science’s investigational stereopure oligonucleotide suvodirsen fast track designation for the treatment of Duchenne muscular dystrophy in patients amenable to exon 51 skipping.1

The drug, which is currently being studied in a global phase 2/3 multicenter study and an open-label extension, had previously been granted orphan drug status and rare pediatric disease designation by the FDA. Notably, the phase 2/3 DYSTANCE 51 study is the first to be selected to participate in the FDA’s Complex Innovative Trial Design pilot program.

“Our goal for Wave’s Duchenne programs is to urgently develop therapies that restore functional dystrophin to levels that have the potential to result in meaningful clinical benefit,” said Michael Panzara, MD, MPH, chief medical officer of Wave Life Sciences, in a statement.1 “We are thrilled to have received Fast Track designation from the FDA for suvodirsen, a decision which we believe reflects its potential to provide a meaningful option for those living with this dreadful genetic disease. We look forward to continuing to work with regulatory authorities with the hope of bringing suvodirsen to the Duchenne community as quickly as possible.”

The phase 2/3 clinical trial (NCT03907072), recently announced in June, is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of suvodirsen in ambulatory patients with DMD amenable to exon 51 skipping. Participants aged 5 to 12 with a genetically confirmed diagnosis of DMD will be randomly assigned to 2 doses of the study drug or placebo. The primary end points are change in dystrophin protein level from baseline to week 12, week 22, or week 46, and change in the North Star Ambulatory Assessment score from baseline to week 48. Other secondary outcomes measures include change in upper limb proximal strength, 4-stair climb, 10-meter walk/run test, forced vital capacity, and 95th percentile stride velocity, all through week 48.

Notably, the drug ran into some concerning tolerability issues during phase 1 when it was reported that patients who were dosed above 5 mg/kg experienced serious treatment-related adverse events including fever, tachycardia, and vomiting.2 While symptoms were resolved with acetaminophen and hydrocortisone, the reaction raised some doubts about whether the drug could produce a clinically meaningful effect at such a low dose.

Suvodirsen is just one investigational therapy in an increasingly crowded pool of potential treatments for Duchenne muscular dystrophy. It targets the same genetic mutation as Exondys 51 (eteplirsen; Sarepta), currently the only FDA-approved therapy for DMD, “skipping” over the targeted exon and restoring truncated, but functional, dystrophin production.  

Pending muscle biopsy results from the open-label study, Wave intends to file for accelerated approval in the second half of 2020.
REFERENCES
1. Wave Life Sciences Announces Fast Track Designation from U.S. FDA for Suvodirsen [news release]. Cambridge, MA: Wave Life Sciences. September 16, 2019. globenewswire.com/news-release/2019/09/16/1915853/0/en/Wave-Life-Sciences-Announces-Fast-Track-Designation-from-U-S-FDA-for-Suvodirsen.html. Accessed September 16, 2019.
2. Wave Life Sciences Muscular Dystrophy Association Clinical and Scientific Conference Investor Update. April 16, 2019. https://ir.wavelifesciences.com/static-files/4b471bd1-5fa2-454f-be89-4af1f05f6a8d. Accessed September 16, 2019.