Wave Life Sciences shared safety and tolerability data from their Phase 1 clinical trial evaluating investigational suvodirsen (WVE-210201) in patients with Duchenne. The results from this trial support progressing to a Phase 2/3 clinical trial, which the company intends to initiate in July 2019.

We are excited for Wave’s continued progress and look forward to learning more about their trial at this summer’s PPMD Annual Conference.

 

Read Wave’s letter to the Duchenne Community:

Dear Duchenne community: 

We are excited to share that on April 16th, 2019, we shared safety and tolerability data from our Phase 1 clinical trial evaluating investigational suvodirsen (WVE-210201) in boys with Duchenne muscular dystrophy. The results from this trial support progressing to a Phase 2/3 clinical trial, which we intend to initiate in July 2019, so we wanted to review what comes next. 

The Phase 1 clinical trial was a placebo-controlled, single ascending dose study to evaluate safety, tolerability and pharmacokinetics of suvodirsen. Thirty -six boys with Duchenne muscular dystrophy amenable to exon 51-skipping therapy were given a single infusion of suvodirsen or placebo and followed by their clinical teams for 85 days. The results of the study demonstrated that a single infusion of suvodirsen was generally safe and well-tolerated at doses up to and including 5 mg/kg and support initiation of a Phase 2/3 trial to evaluate efficacy and safety. 

The Phase 2/3 clinical trial, called DYSTANCE 51, is a global, multi -center, placebo-controlled study designed to evaluate the efficacy and safety of suvodirsen in boys with Duchenne muscular dystrophy amenable to exon 51 skipping. The trial design has been accepted into the FDA’s Complex Innovative Trial Design (CID) Pilot Program. Through the CID pilot program, our goal is to reduce the number of patients required for the study, thereby minimizing the number of patients required in the placebo treatment arm and potentially accelerating completion of the trial. For more information on this study please contact us at clinicaltrials@wavelifesci.com or visit ClinicalTrials.gov here (ClinicalTrials.gov Identifier: NCT03907072). 

Our deepest thanks go to all the courageous boys who participated in the Phase 1 study and the families that support them. In addition, we are ever grateful to all of those in the Duchenne community, including the families, advocacy partners, regulators, and clinicians who have provided invaluable guidance on this program from the very beginning. 

Sincerely, 

Michael Panzara, MD, MPH
Chief Medical Officer

 

Questions and Answers 

What’s next for the suvodirsen clinical program? 

Suvodirsen is currently being evaluated in an ongoing multi -dose open-label extension (OLE) study with boys from the Phase 1 clinical trial. We are also planning to initiate a global Phase 2/3 efficacy and safety trial, called DYSTANCE 51. DYSTANCE 51 is a multicenter, randomized, double-blind, placebo-controlled clinical trial that will enroll ambulatory boys 5 – 12 years of age with Duchenne muscular dystrophy amenable to exon 51 skipping. 

What is suvodirsen? 

Suvodirsen (formerly known as WVE-210201) is an investigational exon 51 skipping stereopure antisense oligonucleotide. Exon skipping is an approach that may restore the DMD mRNA reading frame in people with amenable mutations, resulting in restoration of dystrophin protein. Suvodirsen was developed using PRISM™, our proprietary discovery and drug development platform. 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. 

What is the status of Wave’s other exon skipping research? 

We are advancing a lead candidate for exon 53 are we are actively pursuing research programs designed to skip exons 44, 45, 52, 54 and 55. 

Read Wave’s press release:

Wave Life Sciences Announces Suvodirsen Phase 1 Safety and Tolerability Data and Phase 2/3 Clinical Trial Design

Data to be presented today at 2019 Muscular Dystrophy Association Clinical and Scientific Conference
Phase 2/3 clinical trial for suvodirsen in DMD expected to initiate in July 2019
Interim efficacy data from ongoing open-label extension study expected in H2 2019
Investor conference call scheduled for 7:30 a.m. ET today to discuss Phase 1 results and Phase 2/3 trial design

CAMBRIDGE, Mass., April 16, 2019 (GLOBE NEWSWIRE) — Wave Life Sciences Ltd. (NASDAQ: WVE), a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases, today announced the final results from its Phase 1 clinical trial of investigational suvodirsen (WVE-210201) in boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. The company also announced the design of its planned Phase 2/3 clinical trial of suvodirsen in DMD, DYSTANCE 51. The Phase 1 data and DYSTANCE 51 details will be presented today at the 2019 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in Orlando, Florida.

“We are delighted that suvodirsen’s Phase 1 results demonstrate a favorable safety and tolerability profile that allow us to proceed rapidly into Phase 2/3 clinical development with doses we expect to be within the therapeutic window. Later this year, we expect to report interim efficacy data from the ongoing open-label extension study of suvodirsen and intend to use those data as an important component of a submission for accelerated approval in the United States,” said Michael Panzara, MD, MPH, Chief Medical Officer of Wave Life Sciences. “We truly appreciate the boys and families that made this trial possible.”

Phase 1 Clinical Trial Results
Wave’s Phase 1 clinical trial was a global, multicenter, double-blind, placebo-controlled study designed to evaluate the safety, tolerability and plasma concentrations of single ascending doses of suvodirsen administered intravenously. Thirty-six patients received a dose of 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, 7 mg/kg or 10 mg/kg of suvodirsen (n=26) or placebo (n=10) in five ascending dose cohorts and were followed for 85 days. No serious adverse events, deaths or discontinuations due to adverse events were reported in any study patients treated with suvodirsen.

In December 2018, the company selected an initial dose for the DYSTANCE 51 Phase 2/3 clinical trial based on results from the first four cohorts (0.5 mg/kg – 5 mg/kg) of the Phase 1 clinical trial. Key findings from suvodirsen patients in those four cohorts (n=24) and all placebo patients (n=10) include:

• Suvodirsen was generally safe and well tolerated;
• 67% of patients who received suvodirsen (16/24) and 80% of patients who received placebo (8/10) experienced one or more adverse events;
• The most common adverse events occurring in two or more patients who received suvodirsen were pyrexia, headache, vomiting and tachycardia, consistent with infusion-associated reactions;
• Adverse events in patients receiving suvodirsen were mild to moderate in intensity and resolved spontaneously or with symptomatic treatment;
• No clinically relevant changes were observed in renal or hepatic parameters or platelet levels;
• In patients receiving 5 mg/kg of suvodirsen, the adverse events that occurred within 24 hours of infusion were associated with transient increases in high-sensitivity C-reactive protein and complement factor Bb levels, both of which were resolved within a week; and
• No changes were observed in complement C3 levels.

Based on results of the first four ascending dose cohorts, the independent Safety Monitoring Committee of the Phase 1 clinical trial endorsed continued dose exploration by proceeding to the last planned cohort. Doses of 7 mg/kg or 10 mg/kg of suvodirsen were administered to two patients in the fifth cohort and were associated with similar adverse events as those observed at lower doses but were more severe in intensity. The full data from the Phase 1 clinical trial will be presented in an oral presentation and poster at today’s MDA conference.

“The safety profile of suvodirsen observed in this study is encouraging and supports continued progression to a Phase 2/3 study,” said Kathryn Wagner, MD, PhD, chair of the suvodirsen clinical advisory committee and director of the Center for Genetic Muscle Disorders at the Kennedy Krieger Institute at the Johns Hopkins School of Medicine. “These data, along with Wave’s innovative approach to chemical design and clinical development, make me optimistic about suvodirsen’s potential as a possible DMD treatment.”

Design for Phase 2/3 DYSTANCE 51 Clinical Trial
In a second poster, Wave will present the design of DYSTANCE 51, a global, multicenter, randomized, double-blind, placebo-controlled Phase 2/3 efficacy and safety clinical trial of suvodirsen in DMD patients amenable to exon 51 skipping. This clinical trial is designed to enroll boys who are between 5 and 12 years of age (inclusive) with a genetically confirmed diagnosis of DMD amenable to exon 51 skipping therapy. Patients will be randomized to receive 4.5 mg/kg or 3 mg/kg of suvodirsen or placebo administered intravenously once weekly for 48 weeks. The 4.5 mg/kg dose in DYSTANCE 51 provides approximately the same amount of active ingredient as the 5 mg/kg dose in the Phase 1 clinical trial. Both doses have been selected based on the Phase 1 clinical trial results as well as data from in vitroand in vivo nonclinical studies.

The DYSTANCE 51 primary efficacy endpoints will measure change in dystrophin protein level and change in the North Star Ambulatory Assessment score. In addition, this Phase 2/3 clinical trial will include multiple functional outcome measures as secondary efficacy endpoints. DYSTANCE 51 is expected to be initiated in July 2019 and the company intends to use the results of this trial to seek regulatory approvals globally.

Earlier this year, Wave announced that the DYSTANCE 51 clinical trial was selected for the U.S. Food and Drug Administration (FDA) pilot program for complex innovative trial designs. As a participant in the pilot program, the company has additional opportunities to meet with FDA staff to discuss the design elements of the trial, including the potential use of Bayesian methods to adapt the trial with the aim of allowing for more efficient and productive clinical determinations.

Ongoing Open-label Extension Study
Suvodirsen is currently being studied in an ongoing, multi-dose, open-label extension (OLE) study initiated in August 2018 with patients from the Phase 1 clinical trial. The company expects to report an interim analysis of dystrophin expression from muscle biopsies in boys receiving suvodirsen in the OLE study in the second half of 2019. Data from this analysis are intended to serve as an important component of a submission to the FDA for accelerated approval.

View full press release.