WVE-210201 Shows Potential in Early Phase Assessments for Duchenne Muscular Dystrophy

December 11, 2018

The chief medical officer of Wave Life Sciences provided insight into the investigational DMD treatment.

Mike Panzara, MD, MPH

Last week, Wave Life Sciences announced that its investigational candidate WVE-210201 produced positive results in phase 1 testing for boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.

These findings, Wave announced, were well enough that it has selected a dose for a phase 2/3 clinical trial that the company is planning for the next step. In addition to its final analysis from the phase 1 trial, WVE-210201 is being assessed in an ongoing, multi-dose, open-label extension trial, initiated in August 2018 to those completing the phase 1 trial.

In order to find out more about the agent itself, and what Wave is planning for it going forward, NeurologyLive spoke with Mike Panzara, MD, MPH, the chief medical officer of Wave Life Sciences, in an interview.

NeurologyLive: What does the clinician community need to know about these results and WVE-210201?

Mike Panzara, MD, MPH: These results are exciting for the Duchenne community as there is an enormous unmet need for efficacious therapies in this disease. What we’ve seen in our phase 1 clinical trial in boys with Duchenne muscular dystrophy who are amenable to exon 51 skipping is that the safety and tolerability profile through the first four cohorts supports the initiation of a global, placebo-controlled phase 2/3 clinical trial. Based on these results and pending final analysis, we’ve selected a dose for the phase 2/3 and expect to initiate it in 2019.

We look forward to presenting the data from our phase 1 trial, as well as details on our phase 2/3 trial, at an upcoming scientific meeting.

In addition, we are currently running a multi-dose, open-label extension study of WVE-210201 which is available to patients as they complete the phase 1 trial. The first dystrophin expression data from this open-label study are expected in the second half of 2019. These data are intended to be an important component of a submission to the US FDA for accelerated approval.

While this is early phase data, how does this set up WVE-210201 for later in the development process?

The results provided us with the positive safety and tolerability assessment necessary to make a decision to proceed with our planned phase 2/3 clinical trial and enabled us, pending further analysis, to select a dose this trial. Also, the independent Safety Monitoring Committee of the phase 1 clinical trial endorsed continued dosing in our ongoing open-label extension study.

What makes this agent different than others in the space?

Wave’s nucleic acid compounds are different because they are designed to be stereopure, defined as precisely controlled chirality of each phosphorothioate inter-nucleotide backbone linkage during chemical synthesis. This means that we can more precisely design compounds to interact with proteins that mediate the therapeutic effect of the molecule as opposed to heterogeneous “stereorandom” compounds.

In vitro pharmacology studies demonstrated that WVE-210201 induced greater exon 51 skipping and dystrophin protein expression in patient-derived myoblasts with mutations amenable to exon 51 skipping compared to comparator exon 51 skipping oligonucleotides, including an analogue of eteplirsen.

Was anything particularly exciting or unexpected observed in this trial?

What has been unexpected is the intense interest in participating in this trial and the excitement regarding the announcement. This speaks to the significant need that exists in this disease. We have had enormous support from patient community and for that, we are very grateful.