New ad hoc subgroup analyses of data from the first trial testing Medicinova's MN-166 (ibudilast) in amyotrophic lateral sclerosis (ALS) have given the company "the necessary clinical data for powering assumptions for the next study" and the confidence to seek a meeting with the FDA regarding that trial's design, the company said.

News of the results sent U.S.-listed company shares (NASDAQ:MNOV) 11.8 percent higher to close at $9.35 on Tuesday, echoing a rise in the company's Japan-listed shares (TSE:4875). The drug, an oral, anti-inflammatory and neuroprotective agent marketed in Japan and Korea since 1989 for post-stroke dizziness and asthma, is licensed from Kyorin Pharmaceutical Co. Ltd.

Top-line results from the placebo-controlled study, first announced in December, showed that a 60-mg dose of the drug, combined with a 100-mg daily dose of riluzole, met the study's primary endpoint of safety and tolerability. The combination also demonstrated response rates that suggested "efficacy trends in favor" of ibudilast in the 51 subjects without non-invasive ventilation (NIV) that comprised the company's intent-to-treat population, it said at the time.

The new ad hoc subgroup analyses include data from two groups: an "early ALS subgroup," comprising 31 patients who had either bulbar onset or upper limb onset and an "early ALS + NIV subgroup" which included 39 individuals who had either bulbar onset or upper limb onset. The full analysis set from which the subgroups were drawn included all randomized subjects in the study who received at least 14 days of ibudilast and had at least one post-dose efficacy measurement.

The subgroup analyses were completed for the ALS Functional Rating Scale-Revised (ALSFRS-R) total score, the Assessment Questionnaire (ALSAQ-5) score, which measures the physical mobility, activities of daily living and the Manual Muscle Test, which measures muscle strength. A responder was defined as a trial participant whose score did not worsen at the end of the six-month double-blind period of the study.

Data from the subgroup analyses seemed to track with that of the larger ITT group, detailed in December. During the six-month, double-blind portion of the study presented at that time, 29.4 percent of all participants in the ibudilast group were responders – seeing improved or unchanged ALSFRS-R scores – compared to 17.6 percent of those in the placebo group.

In the new early ALS subgroup data analysis that La Jolla, Calif.-based Medicinova shared, 30 percent (6/20) of participants in the ibudilast group were responders on the ALSFRS-R total score compared to 9.1 percent (1/11) of subjects in the placebo group. There was also a higher percentage of participants who improved in the ibudilast group vs. the placebo group.

In the early ALS + NIV subgroup, 26.9 percent (7/26) of patients in the ibudilast group were responders on the ALSFRS-R total score compared to 7.7 percent (1/13) of those in the placebo group. Just as in the non-NIV early ALS subgroup, a higher percentage of those treated with ibudilast saw improved ALSFRS-R scores than those treated with placebo.

Mirroring data from the full ITT analysis, the percentage of ibudilast + riluzole responders as measured by ALSAQ-5 scores was also significant when compared to the percentage of responders to the placebo and riluzole treatment.

On the Manual Muscle Test (MMT), in the early ALS subgroup, 35 percent of subjects in the ibudilast group were responders on the MMT score compared to 18.2 percent (2/11) of subjects in the placebo group. In the early ALS + NIV subgroup, the figures were similar, with 34.6 percent (9/26) of subjects in the ibudilast group responding on the MMT score compared to 23.1 percent (3/13) of subjects in the placebo group.

Medicinova's CEO, Yuichi Iwaki, said that "we believe this is a direct result of MN-166's mechanism of enhancing the production of neurotrophic factors including nerve growth factor. We look forward to meeting with the FDA."

Medicinova ran the trial in collaboration with Benjamin Rix Brooks, director of the Carolinas Neuromuscular/ALS-MDA Center at Carolinas Healthcare System Neurosciences Institute. A second smaller study at Massachusetts General Hospital testing 100 mg per day of ibudilast is listed in ClinicalTrials.gov as recruiting at its latest update, in April.

In addition to ALS, Medicinova is developing ibudilast for progressive multiple sclerosis, glioblastoma and substance abuse/addiction. It failed to help addicts kick methamphetamine dependence in a phase II study that read out earlier this year, but the company said in May that it was moving forward with plans to initiate a trial in alcohol dependence and withdrawal in collaboration with researchers at the University of California, Los Angeles. (See BioWorld, March 30, 2018.)