The U.S. Food and Drug Administration (FDA) has granted fast track designation to suvodirsen as a treatment for people with Duchenne muscular dystrophy (DMD).

The agency’s decision — which will expedite the review process for suvodirsen — was based on experimental and preclinical data demonstrating the treatment’s potential therapeutic activity.

Suvodirsen already had been granted orphan drug designation for the treatment of DMD by both the FDA and the European Commission. It also received a rare pediatric disease designation by the FDA.

Fast track designation is granted to investigational therapies that aim to treat serious or life-threatening conditions, and show demonstrated potential to address an unmet medical need. Besides frequent interactions with the FDA, this designation includes eligibility for rolling submission of a new drug application to accelerate regulatory review and approval of the new therapy.

DMD is caused by mutations in the DMD gene, which codes for dystrophin, a protein with a key role in the support and protection of muscle fibers. These mutations may disrupt the reading of exons — the DNA bits with instructions to make proteins — leading to the absence of dystrophin.

Suvodirsen, formerly known as WVE-210201, is a so-called exon-skipping therapy being developed by Wave Life Sciences. It is designed to overcome one of the most common causes of DMD: genetic mutations on the exon 51 portion of the DMD gene, which codes for dystrophin protein.

These mutations disrupt the reading of the exon 51 and subsequent parts of the gene, which contain important information for making the protein. This commonly results in the production of deficient versions of dystrophin, or does not allow for the protein to be produced at all.

With a “skip over” exon 51 strategy, it is possible to bypass the effects of the genetic mutations in the DMD gene, resulting in the production of working versions of dystrophin. This means that only patients with mutations in exon 51 would be eligible to receive this treatment.

“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,” Michael Panzara, MD, chief medical officer at Wave Life, said in a press release. “We look forward to continuing to work with regulatory authorities with the hope of bringing suvodirsen to the Duchenne community as quickly as possible.”

Results from a global Phase 1 trial (NCT03508947) that enrolled 36 DMD patients showed intravenous (into the vein) administration of suvodirsen was safe and well-tolerated, although the highest dose tested (10 mg/kg) led to some severe adverse events. The most common adverse events — none of which led to treatment discontinuation — were fever, headaches, vomiting, and fast heartbeat. All events were mild and transient.

An open-label extension study is currently testing suvodirsen in people who took part in the Phase 1 study. Early analysis of dystrophin levels in muscle biopsies of these patients, which should be performed until the end of the year, is expected to provide important clues on the efficacy of this treatment strategy. Pending positive results, the company plans to submit an application for accelerated approval of suvodirsen in the U.S. in the second half of 2020.

Suvodirsen also will be evaluated in DYSTANCE 51 (NCT03907072), a global, double-blind Phase 2/3 trial comparing the efficacy and safety of suvodirsen and placebo in pediatric patients, ages 5 to 12. Two doses are being tested — 4.5 mg/kg and 3 mg/kg — with treatment given every week for a period of 48 weeks. Results from this study are intended to support global regulatory filings of Suvodirsen.

DYSTANCE 51 is the first trial ever selected by the FDA for its Complex Innovative Trial Designs 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,” Panzara said.

Besides suvodirsen, Wave is conducting preclinical tests of WVE-N531, intended to treat people with DMD who are amenable to exon 53 skipping. Other exon targets are being explored, including exons 44, 45, 52, 54, and 55.Jose Marques