Rare Disease Report

DMD Treatment Granted Orphan Drug & Rare Pediatric Disease Designations

AUGUST 16, 2018
Krista Rossi
This morning, August 16, 2018, the US Food and Drug Administration (FDA) granted an orphan drug designation and a rare pediatric disease designation to Wave Life Sciences Ltd.’s WVE-210201 for the treatment of Duchenne muscular dystrophy (DMD), a fatal X-linked genetic neuromuscular disorder.

“We are very pleased to receive these 2 important designations from the FDA and believe they further reinforce the potential of WVE-210201 to help boys suffering from DMD,” said Michael Panzara, MD, MPH, neurology franchise lead of Wave Life Sciences in a recent statement.

Currently, WVE-210201 is being studied in an ongoing, global, multicenter, double-blind, placebo-controlled phase 1 clinical trial that is designed to assess the safety, tolerability, and plasma concentrations of single ascending intravenous doses of the drug in patients with DMD patients who have gene mutations amenable to exon 51 skipping.

Forty patients are anticipated to enroll in the study, including ambulatory and non-ambulatory patients between the ages of 5 and 18. The option to enroll in an ongoing, open-label extension study in which continued treatment with WVE-210201 is received will be available to enrolled patients upon completion of the phase 1 trial.

Primary outcome measures for the phase 1 trial include the number of patients with adverse events (AEs), the severity of AEs, the number of patients with serious AEs (SAEs), and the number of patients who withdraw due to AEs as measured in the timeframe of 85 days (end of study). Secondary outcome measures will include pharmacokinetics (PK) as measured by the maximum observed concentration (Cmax), the time of occurrence of Cmax (tmax), and the area under the plasma concentration-time curve (AUC 0-t) as measured at day 1, day 2, and day 8 of the trial. September 2018 is the trial’s current estimated primary completion date.
 
An investigational stereopure oligonucleotide, WVE-210201 has been shown to induct skipping of exon 51 of dystrophin pre-mRNA in preclinical studies. Since approximately 13% of patients with DMD have genetic mutations that are amenable to treatment with exon 51 skipping therapy, exon-skipping technology has the potential to induce cellular machinery to “skip over” a targeted exon and restore the reading frame, resulting in the production of internally truncated, but functional, dystrophin protein.   

In preclinical Western blot studies, WVE-210201 exhibited 52% dystrophin protein restoration as compared with normal skeletal muscle tissue lysates. In preclinical in vitro experiments, which utilized gymnotic delivery (free uptake) of WVE-210201 in DMD patient-derived myoblasts, the drug displayed efficient exon 51 skipping and dystrophin protein restoration. 

Previously, in July 2018, WVE-210201 was granted an orphan drug designation by the European Commission.

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