Ibudilast May Help Only Bulbar-Onset Patients, Early Analysis of Phase 2 Data Suggests

More amyotrophic lateral sclerosis (ALS) patients survived among those who completed a Phase 2 trial of MediciNova’s Ibudilast (MN-166), compared to those who dropped out of the study, according to an exploratory interim analysis.

But the data, presented at the American Academy of Neurology (AAN) 2017 Annual Meeting in Boston  April 22-28, also showed that the treatment might not benefit patients with limb-onset ALS, as they — in contrast to bulbar-onset patients — continued to deteriorate during the trial.

Further trials are needed to conclude if this subtype treatment response difference is real.

The clinical trial (NCT02238626) included ALS patients who did not require ventilation. The interim analysis involved 47 patients. Patients are randomized to receive either Ibudilast or placebo, in a double-blind manner, for six months.

After that, an open-label extension study allows those in the placebo group to receive the active treatment for six months. When comparing 31 patients who completed the treatment to 16 that dropped out before the start of the open-label part, survival was higher among those who completed the study.

The research team also assessed 26 patients who completed the study, two weeks after they stopped the treatment. Their muscle strength at that interval was compared to that seen when they took their last dose.

While all patients had reduced strength when measuring hip, leg and neck flexion, a subgroup analysis revealed differences between patients with bulbar and limb-onset disease.

Moreover, when looking at the ALS burden of lower motor neurons, it became apparent that patients with limb-onset disease had deteriorated during the study, while no change was seen in bulbar-onset patients. ALS burden was measured using a tool called Brisbane-Sydney UMN-LMN ALS burden scale.

“We are encouraged by the interim data thus far from this exploratory analysis,” Benjamin Rix Brooks, MD, Director of Carolinas HealthCare System’s Neuromuscular/ALS-MDA Center, and the study’s principal investigator, said in a press release.

“This sub-group analysis suggests that the bulbar-onset ALS patient may be a target for future clinical trials because we found no change in lower motor neuron ALS burden on the Brisbane-Sydney UMN LMN ALS Burden Scale in this subgroup, but further analysis is needed as perhaps this is not the only responsive group, but only the group that we can see in a clinical trial designed as we did.”