MediciNova Secures European Patent for MN-166 Plus Riluzole

The European Patent Office will grant MediciNova a patent that covers the combination of MN-166 (ibudilast) and riluzole for the treatment of amyotrophic lateral sclerosis (ALS), MediciNova announced.

The patent, once issued, will cover a wide range of doses and dosing regimens for both medications, and it is expected to be in effect until at least November 2035. MediciNova has received similar patents in the U.S. and Japan.

“We are very pleased to receive notice that this new patent will be granted,” Yuichi Iwaki, MD, PhD, president and CEO of MediciNova, said in a press release. “We believe this new patent could substantially increase the potential value of MN-166.”

MN-166 is an investigational therapy designed to reduce inflammation in the brain, which has been implicated in ALS. Early clinical studies have suggested that MN-166, in combination with riluzole — a long-approved ALS therapy marketed as Rilutek, Tiglutik, and Exservan, depending on its mode of administration — can improve functional ability, quality of life, and survival.

One of the main mechanisms through which MN-166 is thought to work is by preventing the activation of microglia, which is a type of immune cell in the brain. Researchers at MediciNova and other institutions recently reported results of a Phase 1b clinical trial (NCT02714036) that explored how the medication affects the body.

Results were published in NeuroImage: Clinical, in the study, “Ibudilast (MN-166) in amyotrophic lateral sclerosis- an open label, safety and pharmacodynamic trial.”

The trial, conducted at Massachusetts General Hospital in Boston and South Shore Neurological Associates in New York, enrolled 35 people with ALS. Participants were treated with MN-166 at a dose of 100 mg per day for 36 weeks (about eight months). Dose reductions to 60 or 80 mg/day were permitted if participants experienced adverse side effects. Most of the participants were being treated concurrently with riluzole.

The study’s main goal was to evaluate the effect of treatment on microglia, using an imaging technique called [11C]PBR28-PET — basically, a positron emission tomography (PET) scan using a marker that specifically identifies activated microglia. Results showed no significant differences in [11C]PBR28-PET outcomes before and after treatment.

Researchers also assessed the effect of treatment on blood levels of neurofilament light chain, a marker of damage to the nervous system. Results showed no significant change over the course of treatment.

All of the participants experienced at least one adverse event. The most common adverse events related to treatment included nausea, fatigue, insomnia, hot flashes, diarrhea, and other digestive complaints (e.g., bloating).

Ten serious adverse events were reported in six participants; two of the serious adverse events resulted in death. None of these adverse events were deemed likely related to treatment with MN-166; instead, they were judged to be the result of ALS disease progression.

Of the 35 participants, 13 underwent a dose reduction, and 11 of those participants discontinued participation in the trial early. In total, 16 of the participants did not complete the trial. Nearly a third of the total trial participants discontinued due to treatment side effects.

“Overall ibudilast [MN-166] was observed to be safe and showed no drug related [serious adverse events]. However, the tolerability was limited due to GI [gastrointestinal] side effects, fatigue and insomnia,” the researchers concluded.

The team noted that the generally negative efficacy results point to a need for further studies to better understand how the investigational medication affects the body. They also acknowledged that the study is limited by its small size, lack of placebo group, and high discontinuation rates.

“This study was not designed to answer whether ibudilast is clinically effective in ALS,” the researchers added. “These questions are being addressed in COMBAT-ALS, a Phase 2b/3 randomized, placebo-controlled, double-blind, parallel, multi-center study being conducted by Medicinova in the US and Canada (NCT04057898).”

The COMBAT-ALS trial is currently recruiting up to 230 participants, whose disease became evident within the past 1.5 years, and who will be assigned randomly to receive MN-166, or a placebo, as an add-on to riluzole for one year. More information is available here.