Rare Daily Staff

The U.S. Food and Drug Administration granted Wave Life Sciences Rare Pediatric Disease and Orphan Drug designations for WVE-210201 for the treatment of Duchenne muscular dystrophy, a rare, progressive, and fatal genetic disorder.

DMD is caused by a genetic mutation that results in a deficiency of dystrophin, a protein that is essential to healthy muscles. DMD results in muscle weakness from early childhood. Patients with the condition can lose the ability to walk as early as age 10, followed by loss of the use of their arms. The disease leads to premature death in the mid-twenties due to heart and respiratory failure.

Wave’s experimental therapy WVE-210201 is has been shown to induce skipping of exon 51 of dystrophin pre-mRNA in preclinical studies and is intended for the treatment of DMD. Approximately 13 percent of DMD patients 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.

Wave preclinical in vitro experiments of WVE-210201 in DMD patient-derived myoblasts demonstrated efficient exon 51 skipping and dystrophin protein restoration. Preclinical Western blot studies of WVE-210201 demonstrated 52 percent dystrophin protein restoration as compared with normal skeletal muscle tissue lysates.

WVE-210201 is currently being studied in an ongoing global, multicenter, double-blind, placebo-controlled phase 1 clinical trial designed to evaluate the safety, tolerability and plasma concentrations of single ascending doses of WVE-210201 administered intravenously in DMD patients with gene mutations amenable to exon 51 skipping. The trial is expected to enroll up to 40 patients, including ambulatory and non-ambulatory patients, between the ages of 5 and 18 years of age.

Rare Pediatric Disease designation by the FDA is granted in the case of serious or life-threatening diseases affecting fewer than 200,000 people in the United States in which the serious or life-threatening manifestations are primarily in individuals 18 years of age and younger. The designation provides regulatory incentives for companies to develop and market therapies that treat these conditions. If Wave’s WVE-210201 is approved, the company could be eligible for a Priority Review Voucher that can be used to obtain a priority review of a subsequent marketing application.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Ultragenyx and Kyowa Hakko Kirin sold their Priority Review Voucher for $80.6 million.

The Orphan Drug designation would entitle Wave to seven years of market exclusivity in the United States if WVE-210201 is approved. Additional incentives may include tax credits related to clinical trial expenses, exemption from prescription drug user fees and FDA assistance in clinical trial design. The European Commission previously granted orphan drug designation for WVE-210201 in July 2018.

“Our team is motivated by a sense of urgency and compassion for the patients, families and caregivers affected by Duchenne muscular dystrophy and other serious, life-threatening conditions with high areas of unmet need,” said Michael Panzara, Neurology Franchise Lead of Wave Life Sciences. “We are very pleased to receive these two important designations from the FDA and believe they further reinforce the potential of WVE-210201 to help boys suffering from DMD.”

August 16, 2018
Photo: Michael Panzara, Neurology Franchise Lead of Wave Life Sciences

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