MediciNova’s Ibudilast Reduces Retinal Thinning in MS Trial Subjects

 

MediciNova announced today that it received positive Optical Coherence Tomography (OCT) results from its SPRINT-MS Phase IIb trial of MN-166 (ibudilast) in multiple sclerosis (MS) subjects. The results were published in the Multiple Sclerosis Journal.

A total of 28 sites participated in the trial, with 22 sites using Zeiss Cirrus OCT and six sites utilizing Heidelberg Spectralis OCT. In all, 183 subjects were imaged with Cirrus, while 61 were imaged with Spectralis. All of the OCT measures showed less loss of retinal tissue in subjects who received MN-166, compared to a placebo.

Change in peripapillary retinal nerve fiber layer thickness was +0.0424 uM/year for MN166 (ibudilast) versus −0.2630 uM/year for the placebo. Macular volume change was −0.00503 mm3/year for MN-166 compared to −0.03659 mm3/year for placebo in the Spectralis arm. In the Cirrus cohort, macular volume change was −0.00040 mm3/year for MN-166 (ibudilast) compared to −0.02083 mm3/year for the placebo.

“We are very pleased that the positive OCT data has been published,” said Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc. “This data demonstrates that MN-166 can reduce retinal thinning in progressive MS patients and is further evidence of its neuroprotective effect as retinal thinning is associated with brain volume loss and other measures of MS progression.”

However, this is not the only condition that MN-166 is being investigated for, according to news published by the company back in September. MediciNova announced earlier this fall that it had received positive clinical findings for MN-166 for the prevention of chemotherapy-induced peripheral neuropathy (CIPN). The results were published in the journal Cancer Chemotherapy and Pharmacology.

Dr. Janette Vardy, Professor of Cancer Medicine, University of Sydney Concord Cancer Centre in Australia, helped lead the research with MediciNova. The authors of the report found that the co-administration of MN-166 with oxaliplatin appeared to result in the improvement or stabilization of oxaliplatin-induced neurotoxicity.

The open-label, sequential crossover study was conducted to determine if MN-166 could reduce acute peripheral neuropathy symptoms in subjects with cancer – specifically metastatic upper gastrointestinal or colorectal cancer. A total of 14 patients completed two cycles of oxaliplatin-containing chemotherapy, one cycle with conventional chemotherapy, and one cycle of chemotherapy with concurrent MN-166 treatment.

The subjects underwent a series of assessments for neurotoxicity on Day 3 of each cycle. Once they completed a cycle, they were assessed based on scales including the Oxaliplatin-Specific Neurotoxicity Scale (OSNS), the Total Neuropathy Score Clinical (TNSc), the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group—Neurotoxicity (FACT/GOG-Ntx13), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) neuropathy subscale. Across all neurotoxicity measures, most respondents experienced either an improvement or no worsening of neurotoxicity with MN-166 treatment.

“We are very pleased to report positive results from this study,” Iwaki said at the time of the results publication. “Acute neurotoxicity, which predicts chronic CIPN, usually recurs with oxaliplatin chemotherapy and in most cases, patients experience worsening of neurotoxicity symptoms with continued chemotherapy.   What makes this remarkable is that half of participants reported improved symptoms in the acute period and showed improved neurological parameters on clinical assessment with ibudilast treatment.”

MN-166 is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor inhibitor. It is also a phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines. MediciNova is developing MN-166 for a wide range of conditions, including progressive MS, ALS and other neurological conditions.