MN-166 may slow ALS progression over year, trial data suggest
Interim analysis of COMBAT-ALS findings to date hint at ibudilast benefits
MN-166 (ibudilast), an investigational oral treatment for amyotrophic lateral sclerosis (ALS), appears to slow disease progression over up to one year of use, according to an analysis of data in an ongoing Phase 2b/3 clinical trial.
The interim analysis, required under the study’s design, looked into how well findings in standard measures of disease progression at six months of treatment correlated with those reported up to six months later. The trial’s data safety monitoring board (DSMB) reviewed and validated the data, and recommended the COMBAT-ALS (NCT04057898) study continue as planned.
“We believe these results will be valuable in designing studies for rapidly progressing diseases like ALS,” Kazuko Matsuda, MD, PhD, chief medical officer and director of MediciNova, the therapy’s developer, said in a company press release.
“We considered a change in the treatment period, [but] decided to continue the trial with the current treatment plan based on the DSMB’s recommendation,” Matsuda added.
MN-166 is designed to lower inflammation in the brain, protecting neurons
Of the 217 patients who joined the study as of mid-November, 183 have been randomized to 12 months of treatment with MN-166 or to a placebo. Up to 230 patients are expected to enroll at more than a dozen sites across the U.S. and Canada, with top-line trial data expected in 2026.
Results of the analysis were presented at the 35th International Symposium on ALS/MND, held Dec. 6-8 in Montreal. The presentation was titled “COMBAT-ALS Phase 2b/3 Trial of MN-166 (Ibudilast) in ALS: Trial Update and Interim Analysis Results” (page 242).
In ALS, motor neurons, the nerve cells that control voluntary movement, become progressively damaged and die. While the exact causes of the disease are not fully understood, excess inflammation is believed to contribute to its progression.
MN-166 aims to reduce inflammation in the brain, and improve the health and survival of motor neurons. It’s designed to inhibit toll-like receptor 4 and macrophage migration inhibitory factor, two proteins that trigger immune responses. It also blocks proteins that signal for inflammation, which could slow disease progression.
COMBAT-ALS is testing MN-166 against a placebo in adults up to age 80, who began experiencing disease symptoms no more than 1.5 years before entering the study.
Patients are being randomly assigned to receive twice daily MN-166 capsules — at a dose of 30 mg for two weeks and up to 50 mg thereafter — or a placebo for 12 months. All then may choose to either start or continue with MN-166 for six months during the study’s open-label extension.
The trial’s main goal is to compare changes in ALS Functional Rating Scale-Revised (ALSFRS-R) from the study’s start (baseline) through one year of treatment. The scale tracks disease progression by measuring certain aspects of physical function, such as the ability to grab utensils to write, to eat, turn in bed, walk, climb stairs, and to breathe. Lower scores on this scale indicate worse functional status.
Interim analysis hinted at functional gains being sustained for up to one year
An interim analysis was performed when 70 people in each trial arm (treatment and placebo) reached six months of follow-up. A subset of these patients also had results in at least one assessed data point after that time, so researchers set out to compare six-month and 12-month findings in this group.
Positive correlations between these datasets can provide a hint that the benefits seen in the first six months are sustained for up to one year of treatment.
Analysis of Combined Assessment of Function and Survival (CAFS) scores, which combine functional disability and survival, found a strong relationship between data gathered at the two time points, indicating that early trends seen with treatment were predictive of later outcomes. Positive correlations also were observed for total ALSFRS-R scores, as well as in certain ALSFRS-R subscales.
After completing COMBAT-ALS’ extension period, participants can chose to continue with MN-166 via an expanded access program (EAP), MediciNova reported. In the U.S., a limited EAP for MN-166 is due to expand as a trial next year, supported by a $22 million National Institutes of Health grant and managed by Widetrial.
“We look forward to the opportunity to provide access to MN-166 to more ALS patients,” Matsuda said.
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