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
Phase 2/3 clinical trial for suvodirsen in DMD expected to initiate in
Interim efficacy data from ongoing open-label extension study expected in H2 2019
Investor conference call scheduled for
“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
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.
- 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
“The safety profile of suvodirsen observed in this study is encouraging and supports continued progression to a Phase 2/3 study,” said
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 vitro and 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
Earlier this year, Wave announced that the DYSTANCE 51 clinical trial was selected for the
Ongoing Open-label Extension Study
Suvodirsen is currently being studied in an ongoing, multi-dose, open-label extension (OLE) study initiated in
Investor Conference Call and Webcast
Wave management will host an investor webcast and conference call today at
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic neuromuscular disorder caused predominantly by out-of-frame deletions in the dystrophin gene, resulting in absent or defective dystrophin protein. Dystrophin protein is needed for normal muscle maintenance and operation. Because of the genetic mutations in DMD, the body cannot produce functional dystrophin, which results in progressive and irreversible loss of muscle function, including the heart and lungs. Worldwide, DMD affects approximately one in 5,000 newborn boys.
About Suvodirsen (WVE-210201)
Suvodirsen is an investigational stereopure oligonucleotide that has been shown to induce skipping of exon 51 of dystrophin pre-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
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the planned presentation today of the final results from the Phase 1 clinical trial of suvodirsen in DMD, the expected timing of initiation of the Phase 2/3 clinical trial for suvodirsen in DMD, the plans to report interim efficacy data from the ongoing open-label extension study with patients from the Phase 1 clinical trial of suvodirsen in DMD, the belief that the safety and tolerability data from the Phase 1 clinical trial supports initiation of a Phase 2/3 clinical trial, Wave’s intention to use the results of the Phase 2/3 trial to seek regulatory approvals, Wave’s plans and expectations regarding the design of the Phase 2/3 clinical trial, and Wave’s expectations regarding the selection of the Phase 2/3 trial for the
Media and Patient Contact:
Source: Wave Life Sciences