MediciNova Announces Opening of IND for MN-166  for Prevention of Acute Respiratory Distress Syndrome in Patients With COVID-19

MediciNova, Inc. recently announced that the Investigational New Drug Application (IND) for MN-166 (ibudilast) for prevention of Acute Respiratory Distress Syndrome (ARDS) has been accepted and is now open with the US FDA. MediciNova was informed by the FDA that the proposed clinical investigation of MN-166 (ibudilast) for the prevention of ARDS in patients with COVID-19 may proceed.

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented “We are very pleased that this important regulatory step is completed, as we are now pursuing clinical development of MN-166 in patients with COVID-19 who are at risk for developing ARDS. We believe that MN-166 has potential to prevent deaths from COVID-19 by reducing hyperinflammation and cytokine storm. As we previously reported, treatment with MN-166 (ibudilast) reversed histological changes observed in the ARDS mouse model including inflammation, hemorrhage, alveolar congestion, and alveolar wall edema. MN-166 also significantly reduced serum inflammatory cytokines, significantly reduced pulmonary edema in lung tissue, and protected against pulmonary injury by reducing cell apoptosis in lung tissue. In addition to strong evidence from the ARDS mouse model, MN-166 has been identified as a hit compound with potential anti-SARS-CoV-2 effect and its long known anti-thrombotic effect may prevent or treat blood clots in COVID-19 patients, who commonly experience pulmonary embolism. Considering COVID-19’s high infection rate, there is an urgent need to develop an effective and safe treatment in patients at risk of developing ARDS.”

Based on review and discussion with FDA, the design of the Phase 2 clinical trial includes the following elements:

-Randomized (1:1), double-blind, placebo-controlled, parallel group study in hospitalized COVID-19 patients at risk for developing ARDS and receiving standard-of-care including anticoagulation therapy.

-Subjects will be randomly assigned to receive up to 100 mg/day MN-166 or matching placebo for 7 days;

• • Patients will be followed up at Days 14 and 28;
  • The co-primary objectives include the proportion of subjects free of respiratory failure, subjects’ change in clinical status measured by NIAID scale, and plasma cytokine levels after 7 days of treatment;
  • Secondary objectives include safety, tolerability, and the proportion of subjects free of respiratory failure on Day 14.

Major inclusion criteria for trial eligibility will include confirmed SARS-CoV-2 infection, oxygen saturation (SpO₂) ≤92% on room air, chest imaging with abnormalities consistent with COVID-19 pneumonia, and has at least one risk factor that poses a higher risk for more severe illness from COVID-19.

Acute respiratory distress syndrome (ARDS) is a frequently lethal lung condition caused by excessive inflammation for which there are no effective therapies beyond supportive care. Normally, the lung exchanges oxygen for carbon dioxide in small airway sacs called alveoli. In ARDS, there is extensive inflammation and tissue injury in the alveoli of the lungs, and loss of the surfactant, a substance necessary for keeping alveoli open. These changes prevent the lungs from filling properly with air and providing the body with enough oxygen, causing life-threatening difficulty breathing. ARDS may develop over a few days, or it can get worse very quickly. The first symptom of ARDS is usually shortness of breath. Other signs and symptoms of ARDS are low blood oxygen, shallow, and/or rapid breathing.  Infections are the most common cause of ARDS. These infections may include the flu, coronavirus, other viruses, and sepsis.  The rate of death in the hospital is approximately 40% for ARDS patients.

MN-166 (ibudilast) has been marketed in Japan and Korea since 1989 to treat post-stroke complications and bronchial asthma. MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule phosphodiesterases (PDE) 4 and 10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glia cells, which play a major role in certain neurological conditions. Ibudilast’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical study results and provide the rationale for its therapeutic utility in substance use disorders, neurodegenerative diseases (e.g., ALS and progressive MS), and chronic neuropathic pain.  MediciNova is developing MN-166 for various neurological conditions such as progressive MS, ALS and substance abuse/addiction.

MediciNova, Inc. is a publicly traded biopharmaceutical company founded upon acquiring and developing novel, small-molecule therapeutics for the treatment of diseases with unmet medical needs with a primary commercial focus on the U.S. market. MediciNova’s current strategy is to focus on MN-166 (ibudilast) for neurological disorders such as progressive multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and substance dependence (e.g., alcohol use disorder, methamphetamine dependence, opioid dependence) and MN-001 (tipelukast) for fibrotic diseases such as nonalcoholic steatohepatitis (NASH) and idiopathic pulmonary fibrosis (IPF).  MediciNova’s pipeline also includes MN-221 (bedoradrine) for the treatment of acute exacerbations of asthma and MN-029 (denibulin) for solid tumor cancers.  MediciNova is engaged in strategic partnering and other potential funding discussions to support further development of its programs. For more information, visit www.medicinova.com.