Yale to Launch Clinical Trial for Severe COVID-19 Patients with Ibudilast—an Asthma Medication from Japan

Yale to Launch Clinical Trial for Severe COVID-19 Patients with Ibudilast—an Asthma Medication from Japan

Clinical investigators at Yale-New Haven Hospital are investigating the efficacy of ibudilast (MN-166) for treating acute respiratory distress syndrome (ARDS), the life-threatening condition developed by some of the most severe cases seen in COVID-19 patients. These investigators, part of the Yale Advanced Therapy Group—formed in response to the pandemic to identify new treatments addressing the disease—test a drug that has been approved for years in Japan and Korea for the treatment of asthma. The drug has actually shown promise for reducing inflammation associated with ARDS in mouse models.

TrialSite News offers a brief breakdown of this new information.

What is ibudilast (MN-166)?

Also known as AV-41, it is an anti-inflammatory drug used mainly in Japan, which acts as a phosphodiesterase inhibitor, inhibiting the PDE4 subtype to the greatest extent, but also shows significant inhibition of other PDE subtypes. The drug has been used in Japan and is in fact approved for the treatment of asthma and for the improvement of dizziness secondary to chronic cerebral circulation impairment associated with sequela of cerebral infarction.

With a trade name of Ketas, it is marketed by Kyorin Pharmaceuticals Co. in Japan. Idubilast is a type of drug known as a MIF inhibitor. MIF is a gene that regulates the immune response—a driver of inflammation and the so called “cytokine storm.” Over-expression of the gene has been found to play a key role in the number of diseases, including ARDS, asthma, rheumatoid arthritis, lupus, and multiple sclerosis.

What biotech is involved in this development effort?

MediciNova, a California company who has partnered with Yale to launch a clinical trial initially for the treatment of multiple sclerosis and neuroinflammation prior to pivoting due to COVID-19. Now the pair will commence a study to look at the drug’s performance in COVID-19 patients.

Who is MediciNova?

A California biotech and publicly traded, they have been around for a couple decades. They focus on small-molecule therapeutics for the treatment of diseases with unmet medical needs with a specific focus on the U.S. market. Through alliances, primarily with Japanese companies, they hold the rights to a diversified portfolio of clinical and preclinical product candidates. They are based in La Jolla, California—part of San Diego and a notable life science industry cluster.

Has the FDA approved the trial?

No, not yet. But the researchers anticipate FDA approval soon.

Who is the Principal Investigator?

Dr. Geoffrey Chupp, professor of medicine (pulmonary), and director of the Yale Center for Asthma and Airways Disease.

Why are they testing this drug on COVID-19 patients with ARDS?

The most severely ill COVID-19 patients develop ARDS, and this of course triggers a hyper-inflammation and fluid buildup in the lungs that lead to sharp reduction in oxygen levels. These patients need ventilators to support their breathing, and their prognosis for survival has been poor. These investigators hope that the drug will reduce damaging inflammation and mitigate the progression of COVID-19 related ARDS—and in the process diminish lung injury, offering new hope for patients to recover.

As professor Chupp put it: “COVID-19 causes an intense inflammation reaction known as a ‘cytokine storm.’” He continued, “In patients, this presents as COVID-19 related pneumonia or ARDS. If you can modulate that, you can dial back the severity of the illness.”

More study details

Dr. Maor Sauler, assistant professor of medicine (pulmonary) and co-investigator noted, “We have designed a placebo-controlled trial to see if blocking the effects of macrophage inhibitory factor, or MIF, can protect patients with COVID-19 from developing ARDS.”

What is Yale’s connection to research into drugs that interfere with the MIF pathway to target disease?

Dr. Richard Bucala, chief of rheumatology, allergy, and immunology at Yale School of Medicine and rheumatologist-in-chief at Yale-New Haven Health, is a pioneer in this field of medicine. He helped discover drugs that interfere with the MIF pathway to target disease. In fact, Dr. Bucala was the first to clone MIF and its receptor, and he has developed small-molecule MIF inhibitors to treat autoimmune diseases and cancer.

What is Dr. Bucala’s role at Yale? The forthcoming study?

Dr. Bucala directs the Yale Advanced Therapies Group with Dr. Naftali Kaminski, and led the partnership with MediciNova. Kaminski is the Boehringer Ingelheim Pharmaceuticals, Inc. professor of medicine (pulmonary).

Yale Advanced Therapies Group: Active in the war against COVID-19

This new study is just one of many efforts this group is involved with to find new treatments, diagnostics, and targets for combating COVID-19. Recently, the group helped to lay the groundwork for clinical trials of the novel drug sobetirome to treat patients with ARDS, also at Yale-New Haven Hospital.

Lead Research/Investigators

Dr. Geoffrey Chupp, professor of medicine (pulmonary), director of the Yale Center for Asthma and Airways Disease, and principal investigator.

Dr. Maor Sauler, assistant professor of medicine (pulmonary) and co-investigator.

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