MediciNova‘s experimental therapeutic ibudilast (MN-166) may be most effective for treating amyotrophic lateral sclerosis (ALS) in people with a shorter history of the disease, namely those diagnosed less than 18 months before receiving the treatment, a new analysis shows.
The analysis was presented at the 30th International Symposium on ALS/MND in a presentation by Kazuko Matsuda, MD, PhD, MPH, chief medical officer of MediciNova, titled “Interaction (nonuniformity) of ALS progression and the efficacy of MN-166 (ibudilast)” (abstract CLT-25, Page 277).
Ibudilast is a small molecule that targets three distinct proteins in cells — PDE4, PDE10, and MIF — and is thought to reduce levels of inflammatory molecules in the body while increasing levels of neurotrophic factors, which are molecules that can spur the growth of neurons.
The new analysis uses data from a Phase 2 clinical trial (NCT02238626), funded by MediciNova, designed to study the safety and effectiveness of ibudilast as an add-on treatment to Sanofi‘s Rilutek (riluzole), an approved ALS therapy, in people with early or advanced ALS.
The trial recruited 51 patients at various stages of disease and assigned them randomly to six months of treatment with either ibudilast or a placebo, added to the standard treatment Rilutek. The primary goal was to test safety, but secondary efficacy goals also were assessed.
Prior results indicated that a greater percentage of people treated with ibudilast did not experience disease progression, as indicated by no decrease in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R).
However, the average change in ALSFRS-R scores from the beginning of the study to six months of treatment was not significantly different in ibudilast and placebo-treated patients, likely due to a significant person-to-person variation – rate of disease progression, ALS form, and dispersing ALSFRS-R scores at the start of the trial.
This led to the question of whether certain people might be more likely to benefit from treatment with ibudilast. Specifically, researchers suspected that ALS history — the time from ALS onset — could predict responses to treatment.
To find out, they re-analyzed data from this clinical trial using statistical models that took into account ALS history. For the purposes of this analysis, participants were deemed to have a short history (less than 600 days since ALS onset), or a long history (more than 600 days).
The first analysis was done using data collected prior to treatment start. Among people with a short ALS history, there was a strong negative correlation between history length and ALSFRS-R score — that is, for people who had not had ALS for a very long time, those who had experienced disease onset relatively longer ago were more likely to report more severe disease.
But this correlation wasn’t as strong in people with a long ALS history. In essence, the analysis suggests, ALS tends to get worse with time, but this is reliably predictable only early in the disease.
Based on this, the researchers looked at changes in the ALSFRS-R score over time after treatment began and only in people with a short ALS history. They found that, for people in this group who were given placebo, there was the same kind of correlation; as time went on, disease scores worsened. However, for those on ibudilast, this correlation was not observed.
This suggests, that, “The efficacy of MN-166 is expected to be effective in patients with a short ALS history,” researchers wrote in their abstract.
In a press release, Yuichi Iwaki, MD, PhD, the president and CEO of MediciNova, said “We are very pleased to present these additional analyses from the completed ALS trial. The conclusions from this work and our other analyses completed previously have already been incorporated into the design of our Phase 3 trial. We believe our improved study design, which includes only ALS subjects with symptom onset of less than 18 months, gives this trial a much higher probability of success.”