Date: 2017-11-06
Type of
information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: Wave LIfe Sciences (USA - MA)
Product: WVE-210201
Action
mechanism:
- exon skipping/antisense oligonucleotide. WVE-210201 is an investigational stereopure antisense oligonucleotide that has been shown to induce skipping of exon 51 of dystrophin pre-mRNA in nonclinical studies and is intended for the treatment of DMD. Approximately 13% 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 pre-clinical in vitro experiments using gymnotic delivery (free uptake) 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% dystrophin protein restoration as compared with normal skeletal muscle tissue lysates, versus approximately 1% when testing other exon-skipping compounds.
Disease: Duchenne muscular dystrophy (DMD)
Therapeutic
area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: France, UK, USA
Trial
details:
- The Phase 1 study is a multicenter, double-blind, placebo-controlled 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.
- Wave’s first global clinical trial in DMD is expected to enroll up to 40 patients between the ages of 5 and 18 years. The Phase 1 inclusion criteria allow for participation of both ambulatory and non-ambulatory patients, including those previously treated with eteplirsen following an appropriate washout period. The trial has been initiated in the United States, with Europe and other regions to follow. Intravenous doses tested in the Phase 1 trial will escalate through a range expected to be clinically relevant. In the U.S., Wave is required to provide data from ongoing preclinical studies to the FDA in order to progress to the highest dose cohorts and planned multi-dose studies.
- (NCT03508947)
Latest
news:
- • On November 6, 2017, Wave Life Sciences announced the initiation of a global Phase 1 clinical trial for WVE-210201 in Duchenne muscular dystrophy (DMD) patients amenable to exon 51 skipping. This clinical trial marks the next stage in the company’s ongoing commitment to address the significant unmet needs of patients diagnosed with this devastating disease and it is the company’s third clinical trial initiated in 2017.
- Data from the Phase 1 trial for WVE-210201 are expected in Q3 2018 and will facilitate the rapid transition to a double-blind, placebo-controlled, multi-dose efficacy study where dystrophin expression and clinical outcomes will be assessed. The clinical program is designed to allow patient participants in the Phase 1 trial to enroll in an open-label extension study in which dosing with WVE-210201 will continue. The open-label extension study and the planned efficacy study are each intended to follow the Phase 1 trial and expected to include an interim efficacy readout of dystrophin expression from muscle biopsies in 2H 2019.
- In addition to its exon 51 program, Wave is leveraging its stereopure chemistry platform to advance investigational therapies targeting additional DMD-related exons. In September 2017, Wave announced that its next DMD development program will target exon 53 and is expected to initiate clinical trials in Q1 2019. In addition, the company is exploring both intravenous and subcutaneous administration for the WVE-210201 and exon 53 programs.
Is
general: Yes
