Merit Cudkowicz, MD, MSc

“I think the potential for this drug, in this phase 1 trial, is that we’re going to identify the dose that hits target and is safe so that we can move forward to the pivotal efficacy trial.”

Dosing recently began for patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in the phase 1b/2a FOCUS-C9 trial (NCT04931862). The study will evaluate a new investigational treatment, WVE-004, which was developed by Wave Life Sciences to focus specifically on patients with 

-associated ALS (C9-ALS) and FTD (C9-FTD).

The chair of the clinical advisory board for the trial, Merit Cudkowicz, MD, spoke with 

 on the design of the trial, what makes it unique, and the potential for clinical outcomes. Cudkowicz, who is also director of the Sean M. Healey & AMG Center for ALS and the chief of neurology at Massachusetts General Hospital, commented on the trial’s adaptive, basket design, as it includes patients with C9-ALS, as well as patients with C9-FTD. 

The “innovate design,” according to Cudkowicz, looks into polyGP dipeptide repeat proteins in the cerebrospinal fluid and the effectiveness of WVE-004 in reducing that marker. Clinical data from the study are expected to be generated through 2022, with dose escalation and dosing frequency dependent on analysis from an independent data safety monitoring board. 

Wave Life Sciences announces initiation of dosing in phase 1b/2a FOCUS-C9 clinical trial of WVE-004 in amyotrophic lateral sclerosis and frontotemporal dementia. News release. July 20, 2021. Accessed August 6, 2021. https://www.globenewswire.com/news-release/2021/07/20/2265597/0/en/Wave-Life-Sciences-Announces-Initiation-of-Dosing-in-Phase-1b-2a-FOCUS-C9-Clinical-Trial-of-WVE-004-in-Amyotrophic-Lateral-Sclerosis-and-Frontotemporal-Dementia.html

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The director of the Sean M. Healey & AMG Center for ALS outlined the trial, which will evaluate ideal dose level and frequency of the investigational treatment for patients with C9-ALS and C9-FTD. 

WVE-004 Treatment for C9orf72 ALS and FTD: Merit Cudkowicz, MD

“We selected people who were rapid progressors, and the reason for that was really 2-fold—1 is that’s the group we saw the best response in, in the phase 2 study, and also because in a 6-month period, that’s the group you’re more likely to see an effect in.”

In late 2020, BrainStorm Cell Therapeutics announced the topline results from its randomized, double-blind placebo-controlled phase 3 trial evaluating NurOwn (mesenchymal bone marrow stromal cells secreting neurotrophic factors) as a treatment for amyotrophic lateral sclerosis (ALS). The findings, while suggesting that the therapy was generally well-tolerated, did not achieve statistically significant results. The primary end point was achieved in 34.7% of NurOwn participants versus 27.7% of the placebo group (

The treatment was assessed in a population of rapidly progressing patients with ALS, investigator Merit Cudkowicz, MD, MSc, told 

, and did display a numerical improvement in the treated group compared to placebo across the primary and key secondary efficacy end points. Notably, the trial met the expected 35% NurOwn treatment group efficacy response assumption, though there was a high placebo response that exceeded placebo responses observed in contemporary ALS trials.

To find out more about the trial and what the clinical community should take away from these findings in light of the lack of statistical significance, 

 interviewed Cudkowicz, who is the director of the Healey & AMG Center for ALS and chief of the department of neurology at Massachusetts General Hospital.

REFERENCE
BrainStorm Announces Topline Results from NurOwn® Phase 3 ALS Study. News release. November 17, 2020. Accessed January 4, 2021. https://ir.brainstorm-cell.com/2020-11-17-BrainStorm-Announces-Topline-Results-from-NurOwn-R-Phase-3-ALS-Study

The director of the Healey & AMG Center for ALS spoke to the recent topline results of a phase 3 study of NurOwn in patients with the neuromuscular disease.

Merit Cudkowicz, MD, MSc

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