Suvodirsen For Duchenne Muscular Dystrophy Selected for FDA Complex Innovative Trial Designs Pilot Program

January 3, 2019

Wave Life Sciences Ltd. (NASDAQ: WVE announced on 1/3/19 that the planned Phase 2/3 efficacy and safety trial for its lead Duchenne muscular dystrophy (DMD) clinical program has been selected for the U.S. Food and Drug Administration (FDA) pilot program for complex innovative trial designs (CID). The selection was based on the design of Wave’s Phase 2/3 clinical trial of suvodirsen (WVE-210201), an investigational therapy for boys with DMD who are amenable to exon 51 skipping. This marks the first time that the FDA has selected clinical protocols for its CID pilot program that was announced in August 2018.

In evaluating submissions for the CID pilot program, the FDA considered two key criteria: the innovative features of the trial design and the therapeutic need (i.e., therapies being developed for use in disease areas where there are limited or no treatment options). Wave’s application for the CID pilot program includes a plan to leverage DMD historical control data to augment the placebo arm of the suvodirsen Phase 2/3 clinical trial, among other innovative design elements. Through this pilot program, Wave intends to reduce the number of patients required to deliver conclusive clinical efficacy results, thereby minimizing the number of patients required in the placebo treatment arm and potentially accelerating study completion. As a participant in the pilot program, the company will also have additional opportunities to meet with FDA staff to discuss the design elements of the trial, including the use of Bayesian methods to adapt the trial and allow for more efficient and productive clinical determinations. Details of Wave’s Phase 2/3 trial design will be presented at upcoming scientific meetings.

“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,” said Michael Panzara, MD, MPH, Chief Medical Officer of Wave Life Sciences. “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.”

Wave anticipates initiating the global, placebo-controlled Phase 2/3 efficacy and safety clinical trial of suvodirsen in DMD patients amenable to exon 51 skipping in 2019. The trial is designed to measure clinical efficacy and dystrophin expression, and Wave intends to use the results of this trial to seek regulatory approvals globally. Currently, suvodirsen is being studied in an ongoing open-label extension (OLE) study and Wave expects to deliver an interim analysis of dystrophin expression from this study in the second half of 2019.

The FDA CID pilot program is an initiative under the 21st Century Cures Act, with an objective to modernize clinical trial design, help streamline and advance drug development and inform easier regulatory decision-making. In order to qualify for the CID pilot program, companies must intend to provide substantial evidence of efficacy through a complex, novel design that incorporates innovative trial design elements such as seamless trial designs, modeling and simulations to assess trial operating characteristics, the use of biomarker enriched populations, complex adaptive designs, Bayesian models and other benefit-risk determinations, among others.

Suvodirsen is an investigational stereopure oligonucleotide that has been shown to induce skipping of exon 51 of dystrophinpre-mRNA in preclinical studies and is intended for the treatment of Duchenne muscular dystrophy (DMD). Approximately 13% of DMD patients have genetic mutations that are amenable to treatment with an 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 using gymnotic delivery (free uptake) of suvodirsen in DMD patient-derived myoblasts demonstrated efficient exon 51 skipping and dystrophin protein restoration. Preclinical Western blot studies of suvodirsen demonstrated 52% dystrophin protein restoration compared with normal skeletal muscle tissue lysates. Suvodirsen has been granted orphan drug designation for the treatment of DMD by the U.S. Food and Drug Administration (FDA) and the European Commission, as well as rare pediatric disease designation by the FDA.

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