The treatment was safe and well-tolerated – meeting the trial’s primary endpoint – and was found to be more effective at improving patients’ function than the placebo.
Results were showcased as an oral presentation, titled, “Ibudilast: Bi-modal therapy with riluzole in early and advanced ALS patients,” at the 28th International Symposium on ALS/MND (Motor Neurone Disease) held Dec. 8-10 in Boston.
MediciNova conducted a clinical trial (NCT02238626) in conjunction with the Carolinas Neuromuscular/ALS MDA Center at Carolinas HealthCare System Neurosciences Institute to evaluate the effect of administering 60 mg of MN-166 in early and advanced ALS patients.
Patients were randomized to receive either MN-166 or placebo. All patients received 100 mg of Rilutek (riluzole), an approved drug for the treatment of ALS.
The trial achieved the primary endpoint of safety and tolerability, and demonstrated efficacy towards MN-166.
MN-166 is a small molecule phosphodiesterase (PDE)-4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) that reduces pro-inflammatory cytokines and promotes neurotrophic factors. As a result, it decreases inflammation and encourages the development and function of neurons.
Seven serious adverse events were reported during the study, none of which were related to MN-166. All adverse events related to the treatment were mild to moderate with no severe or life-threatening events. The most common adverse events were nausea, anorexia, and loss of appetite, which are side effects of both Rilutek and MN-166 treatment.
Efficacy was determined using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score, which measures the functional activity of an ALS patient. A responder is a patient who either has an improvement in the ALSFRS-R score, no change in score, or declines by 1 point. A non-responder is a patient who declines by 2 or more points.
During the first six months, 29.4% of patients in the MN-166 group were responders, compared to 17.6% of patients in the placebo group. Among patients who switched from placebo to MN-166 in the open-label six-month extension period, 35.3% were responders when taking MN-166.
Another method of determining efficacy was the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) score, which measures physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional functioning. Responders in this test are defined as those who improved on the score or had no change, while non-responders were those who showed declined scores.
While half of patients in the MN-166 group were responders, only 23.5% of patients in the placebo group were responders. For patients treated with placebo, switching to MN-166 in the open-label extension period led to 29.4% of these patients becoming responders. In total, 43.1% of patients treated with MN-166 were responders, compared to 23.5% of patients on the placebo.
“The results of this study are very encouraging and indicate that MN-166 has the potential to stop disease progression and improve functional activity in some ALS patients. This is an impressive effect that has not been observed in studies of other drugs for ALS,” Dr. Benjamin Rix Brooks, principal investigator of the study, said in a press release.
“We are very pleased with the top-line data as this study achieved both goals we set out to achieve: (1) MN-166 was safe and well tolerated in ALS, and (2) MN-166 demonstrated efficacy trends that warrants further investigation in a larger ALS study,” said Yuichi Iwaki, MD, PhD, president and CEO of MediciNova.
There is currently a second trial of MN-166 in ALS patients in an ongoing Phase 1/2 biomarker study at Massachusetts General Hospital. This study is using a higher dose of 100 mg of MN-166 per day (NCT02714036).