MediciNova’s Drug Flunks Phase II Trial

La Jolla, California-based MediciNova announced that its Phase II clinical trial of ibudilast (MN-166) failed to meet its primary endpoint for methamphetamine dependence.

The drug, ibudilast, has been on the market in Japan and Korea since 1989 to treat bronchial asthma and post-stroke complications. The company is also developing it for progressive multiple sclerosis (MS) and other neurological disorders, such as ALS and substance abuse/addiction. It is an oral phosphodiesterase (PDE) -4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. The drug is involvedin five other ongoing Phase II clinical trials.

The study was being evaluated at a UCLA research clinic in treatment-seeking people with methamphetamine dependence, stratified by HIV serostatus. Patients eligible were either given 100 mg/day of ibudilast or a placebo for 12 weeks, with twice-weekly counseling visits, urine drug tests, and safety/medication adherence monitoring. The focus was on a statistically significant benefit over placebo of methamphetamine abstinence during the last two weeks of the trial—which was not observed.

On a positive note, which might be useful for the studies of the drug for other indications, there were no serious or severe side effects in the group receiving the drug. The most common related side effect was gastrointestinal adverse events.

"We will conduct further analyses of the data with UCLA researchers, which will help us to better understand how to optimize study design and setting for any future clinical trials in substance dependence," said Yuichi Iwaki, MediciNova’s president and chief executive officer, in a statement. "We will discuss the results with NIH/NIDAwho provided the funding for this trial, the opioid dependence trials and the alcohol dependence trial. We plan to meet with FDA after we have data from the ongoing study of MN-166 in methamphetamine use disorder at Oregon Health & Science University."

Not surprisingly, company shares were down about 15 percent in premarket trading.

Yesterday the company announced it was planning a pilot study to evaluate ibudilast in chemotherapy-induced peripheral neuropathy with researchers in Australia. The company will work with Janette Vardy, professor of Cancer Medicine, University of Sydney Concord Cancer Centre in Australia. A grant from the Concord Cancer Centre Research will fund the study along with MediciNova.

The trial will assess the drug’s neurotoxicity and drug interactions in 20 patients with metastatic gastrointestinal cancer (colorectal cancer and upper GI cancers) that are receiving oxaliplatin. The goal is to see if ibudilast can prevent acute neurotoxicity, determine the pharmacokinetics of the drug with oxaliplatin and fluorouracil, and whether it might decrease the severity of chemo-induced peripheral neuropathy.

"This is an exciting new project and we are enthusiastic to partner with MediciNova to evaluate MN-166 in chemotherapy-induced peripheral neuropathy patients," said Vardy in a statement. "As chemotherapy-induced peripheral neuropathy is believed to be caused by glial activation, we believe ibudilast’s ability to reduce glial activation could be beneficial in treating this common disorder following chemotherapy."

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