On January 8, 2019 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that the first glioblastoma patient has enrolled in the clinical trial of MN-166 (ibudilast) in combination with temozolomide (TMZ, Temodar‑) for the treatment of recurrent glioblastoma (GBM) (Press release, MediciNova, JAN 8, 2019, View Source;p=RssLanding&cat=news&id=2382746 [SID1234532592]). The principal investigators are Patrick Y. Wen, M.D., Professor of Neurology, Harvard Medical School and Director, Neuro-Oncology Division at the Dana-Farber Cancer Institute (DFCI) in Boston, and Kerrie McDonald, Ph.D., Associate Professor and Head of Biomarkers and Translational Research at the Lowy Cancer Research Centre, University of New South Wales, Australia.
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The scientific rationale for this clinical trial is based on positive results from preclinical studies conducted by Dr. McDonald and her team. MN-166 (Ibudilast) and temozolomide (TMZ) combination treatment significantly increased GBM cell apoptosis and cell cycle arrest in an in-vitro study. Combination treatment of MN-166 (ibudilast) with TMZ resulted in significantly extended survival times compared to TMZ monotherapy in a GBM animal model study with complete tumor regression observed in two out of 16 mice. This is the first clinical trial to evaluate the safety, tolerability and preliminary efficacy of MN-166 (ibudilast) in combination with temozolomide for the treatment of recurrent GBM.
Patrick Y. Wen, M.D., principal investigator, commented, "We are very excited to study ibudilast with TMZ combination treatment as we believe ibudilast’s mechanisms of action and good penetration of the blood-brain barrier could benefit patients with recurrent GBM."
Kerrie McDonald, Ph.D., Associate Professor, University of New South Wales, Australia, commented, "Earlier studies indicate that macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE)-4 may factor in proliferation of GBM tumors. MIF was found to be highly expressed within GBM cells, and especially around necrotic areas and in close proximity to blood vessels. Ibudilast in combination with TMZ resulted in significant blockage of MIF expression, increased apoptosis, and longer survival in vivo."
Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, "We are very pleased that enrollment has commenced for this trial at Dana-Farber Cancer Institute, one of the most highly rated cancer treatment institutions in the U.S. We believe MN-166 offers a novel approach to treating GBM, a highly lethal form of cancer that develops from glial cells."
About the Clinical Trial
This Phase 1/2 clinical trial is divided into a dose-escalation phase (Part 1) followed by a fixed-dose phase (Part 2). A total of 15-18 adult subjects are planned to be enrolled in Part 1 and approximately 32 subjects are planned to be enrolled in Part 2. Part 1 will evaluate the safety and tolerability of MN-166 (ibudilast) when given in combination with TMZ, and determine the dose of MN-166 (ibudilast) to be used in Part 2 of the study. Part 2 will evaluate the efficacy of MN-166 (ibudilast) and temozolomide combination treatment in patients with recurrent GBM as measured by the proportion of patients who are progression-free at 6 months. Other outcome measures include the evaluation of overall survival, response rate, and median six-month progression-free survival.
About Glioblastoma
According to the American Association of Neurological Surgeons, GBM is a devastating brain cancer that typically results in death in the first 15 months after diagnosis. GBM develops from glial cells (astrocytes and oligodendrocytes) and rapidly grows and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents 15% of all brain tumors and 56% of all gliomas and has the highest number of cases of all malignant tumors, with an estimated 12,760 new cases predicted for 2018. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy, and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with GBM. Median survival is 14.6 months and two-year survival is 30%. Approximately 5% of GBM patients survive longer than 36 months.
About MN-166 (ibudilast)
MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glial cells, which play a major role in certain neurological conditions. MN-166 (ibudilast)’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, which provide the rationale for treatment of progressive multiple sclerosis (MS) and other neurological diseases such as amyotrophic lateral sclerosis (ALS), substance abuse/addiction and glioblastoma (GBM). MediciNova is developing MN-166 for progressive MS and other neurological conditions such as ALS, substance abuse/addiction, chemotherapy-induced neuropathy, and glioblastoma. MediciNova has a portfolio of patents which cover the use of MN-166 (ibudilast) to treat various diseases including progressive MS, ALS, and drug addiction.