LA JOLLA, Calif.—The U.S. Food and Drug Administration has granted biopharmaceutical company MediciNova Inc. approval to begin a clinical trial of MN-166 (ibudilast), its drug candidate for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.
The trial will be a randomized, double-blind, placebo-controlled study consisting of a six-month treatment period followed by a six-month open-label extension. The trial will have several efficacy endpoints, including functional activity, respiratory function, muscle strength and non-invasive ventilation utilization, and will also monitor the safety and tolerability of MN-166 60 mg/day versus placebo when administered with riluzole, the only pharmaceutical treatment currently approved for ALS. Once the double-blind phase is complete, the patients in the placebo arm will continue for another six months, in which they will receive open-label MN-166.
Dr. Benjamin Rix Brooks, director of the Carolinas Neuromuscular/ALS-MDA Center at Carolinas HealthCare System Neurosciences Institute, will head the trial as principal investigator. He noted in a press release that “We are excited to initiate this study of ibudilast, which targets a disease with limited treatment options. Ibudilast has demonstrated attenuating effects on activated glia cells, which are considered to play a key role in disease progression in ALS patients.”
MN-166 is a first-in-class, orally bioavailable, small-molecule phosphodiesterase (PDE)-4 and –10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor. The compound suppresses pro-inflammatory cytokines such as IL-1ss, TNF-a and IL-6, and upregulates the release of anti-inflammatory cytokine IL-10 and neurotrophic factors such as NGF and GDNF. MN-166 works to attenuate the activation of brain glial cells in some neurological conditions. Given its therapeutic properties, the compound has a strong basis for therapeutic use in neurodegenerative diseases, substance abuse/addition and chronic neuropathic pain. MN-166 has been on the market in Japan and Korea since 1989 for the treatment of cerebrovascular disorders such as bronchial asthma and post-stroke complications. MediciNova has licensed the compound from Kyorin Pharmaceutical for potential use in multiple sclerosis.
“We are very pleased to have successfully completed the FDA review period and look forward to initiating patient enrollment this fall. The safety and efficacy data from this trial will be important to our overall development efforts and should be complementary to efforts underway for proof-of-concept trials of MN-166 in progressive MS and drug addiction in the U.S.,” Dr. Yuichi Iwaki, president and CEO of MediciNova, commented in a statement. “While MN-166 development is addressing unmet medical needs in all of its neurological indications, ALS may represent the largest unmet medical need.”
ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. The nerves eventually lose their ability to trigger specific muscles, leading to muscle weakness and loss of voluntary movement, to the point of total paralysis. Patients with ALS, of which there are approximately 30,000 in the United States, have a life expectancy of two to five years. Roughly 5,600 people in the United States receive a diagnosis of ALS every year. Riluzole exists as the only treatment option for ALS patients, but unfortunately, the drug “only modestly extends survival by two to three months,” according to the ALS Association.
The disease has recently been catapulted into the public eye thanks to the ALS Ice Bucket Challenge, which was started by an ALS patient, family and friends in hopes of raising awareness. The fundraising effort began at the tail end of July, and between July 29 and August 25, the ALS Association has raised $79.7 million from roughly 1.7 million donors, according to TIME—a figure that tops the organization’s donations for all of 2013, which came in at $64 million.