New Coronavirus Therapeutics and Vaccine Development Trends
The new coronavirus infectious disease “COVID-19” spreads around the world. Summary of development trends for therapeutic drugs and vaccines.
The candidates for the treatment of COVID-19 are Lemdecivir (Gilliad Sciences, Inc.), Fabipiravir (Avigan by Fujifilm Toyama Chemical), and the anti-HIV combination drug lopinavir / ritonavir. (Kaletra, AbbVie, U.S.A.), ciclesonide for asthma (Orbesco, Teijin Pharma), hydroxychloroquine for lupus erythematosus / systemic lupus erythematosus (Planikel, Sanofi, France), and nafamostat for pancreatitis "Fusan" etc.)-and so on.
Lemdesibir (Gilliad, USA)
Remdecivir is an antiviral drug originally developed as a treatment for Ebola. It has been shown to have antiviral activity against single-stranded RNA viruses, including coronaviruses, and is one of the most promising drugs for COVID-19.
At present, doctor-led clinical trials are being conducted in China (China-Japan Friendship Clinic) and the US (National Institute of Allergy and Infectious Diseases = NIAID), and the National Center for Global Health and Medicine will participate in NIAID-led clinical trials. In Japan, we are conducting clinical trials of lemdecivir.
Separately, Gilead is conducting Phase 3 clinical trials (P3) in countries around the world, including Japan. Gilead's trials are expected to complement the data from doctor-led clinical trials in China and the US, and according to Gilead, doctor-led clinical trials in China are expected to be available in April.
Favipiravir (“Avigan” of Fujifilm Toyama Chemical)
Favipiravir is an anti-influenza virus drug approved in Japan in 2014. It is not available on the market because it can only be used in the event of a pandemic flu, but the state reserves 2 million people in preparation for the flu.
Favipiravir is a drug that suppresses virus growth by inhibiting RNA polymerase, a gene replication enzyme of influenza virus. Since the new coronavirus that causes COVID-19 is the same RNA virus as the influenza virus, it is expected that it may have an effect.
However, since teratogenicity has been confirmed in animal experiments, it cannot be used for pregnant women or people who may be pregnant, and if there is a possibility of becoming pregnant, it is necessary to ensure birth control for both men and women there is.
In Japan, Fujifilm Toyama Chemical announced on March 31 that it had started a P3 study in Japan for COVED-19. According to information posted on the clinical trial registration site, approximately 100 COVID-19 patients who developed non-severe pneumonia verified the effect of adding Favipiravir to standard pneumonia treatment. FUJIFILM Toyama Chemical has already started production of Avigan and is preparing to increase production. Denka, which is the only country in Japan to produce dimethyl malonate, which is the raw material for avigan, will resume production in May at the request of the Japanese government.
In China, which was preceded by a medical institution-led trial, the results have been announced as showing effectiveness. FUJIFILM has also begun P2 testing of Avigan for COVID-19 in the United States. The Government of Japan has a policy to provide Avigan free of charge to countries where it wishes, and expects to provide it to 50 countries.
Ciclesonide (Teijin Pharma's "Orbesco")
Ciclesonide is an inhaled steroid approved in Japan in 2007 for the treatment of bronchial asthma. Experiments by the National Institute of Infectious Diseases have shown strong viral activity, and there have been reports of cases in which pneumonia improved when administered to patients.
In Japan, observational studies led by the Japanese Society for Infectious Diseases are being conducted, and reports are being collected from medical institutions around the country to evaluate the effectiveness. At the request of the Ministry of Health, Labor and Welfare, Teijin Pharma has secured a supply of ciclesonide for this study. The National Center for Global Health and Medicine also plans clinical research.
Lopinavir / ritonavir combination (AbbVie's "Kaletra")
Pinavir is a protease inhibitor that suppresses the growth of the virus, and ritonavir maintains its blood levels and enhances its effectiveness. Kaletra, a combination of these drugs, was approved in Japan in 2000 for the treatment of HIV infection.
In vitro and animal model studies have shown efficacy for MERS, suggesting that COVID-19 may also be effective in virtual screening. According to CrinicalTrials.gov, several clinical trials have been conducted in patients with COVID-19 mainly in China, but a Chinese research group reported on March 18 in the U.S. medical journal The New England Journal of Medicin's results showed that there was no difference in the time to clinical improvement compared to the group without Kaletra.
Anti-IL-6 receptor antibody / JAK inhibitor
With the expectation of improving the effect of severe respiratory disorders by suppressing cytokine storms (excessive immune response), drugs that suppress immunity are being developed for severe pneumonia caused by the new coronavirus.
In April, Roche of Switzerland started P3 testing of the anti-IL-6 receptor antibody tocilizumab (product name "Actemra") created by Chugai in the United States, Canada, and Europe. Chugai will soon start a P3 test in Japan. Regeneron Pharmaceuticals of the United States and Sanofi of France are also conducting a P2 / 3 study of the jointly developed anti-IL-6 receptor antibody salilumab (Kevzala) in Europe and the United States. The test is expected to start in Japan soon. Both drugs are mainly used in Japan for the treatment of rheumatoid arthritis.
Novartis, Switzerland, announced on April 2 that it is preparing a P3 study of the JAK inhibitor ruxolitinib (Jakavi) in patients with COVID-19 with a cytokine storm. In Japan, it has been approved for the indication of myelofibrosis and polycythemia vera, and the company commented, "We will consider delivering to patients who need it while complying with Japanese regulations." Among JAK inhibitors, tofacitinib (Pfizer's Xeljanz) is also undergoing physician-led P2 trials in Italy.
The national government has announced that the anti-malarial drug chloroquine phosphate has shown a certain effect on COVID-19, and in Japan, there were reports of cases in which administration of hydroxychloroquine similar to the drug improved symptoms. Gunma University has begun clinical research on triple therapy with lopinavir, ritonavir and hydroxychloroquine. The University of Tokyo Institute of Medical Science announced that Nafamostat may block the entry of SARS-CoV-2, the causative virus of COVID-19, into cells. He will start clinical research soon.
While the development of therapeutic drugs is progressing using an approach that diverts existing drugs, there is a growing movement to develop new drugs.
Takeda Pharmaceutical Co., Ltd. announced on April 6 that it will partner with five companies, including CSL Behring, Inc., to develop advanced immunoglobulin preparations against the causative virus SARS-CoV-2. The six companies will cooperate in a wide range of activities, from the collection of raw material plasma to the planning, implementation and manufacture of clinical trials, and jointly develop and supply unbranded anti-SARS-CoV-2 advanced immunoglobulin preparations. Takeda had revealed that it had started the development of an anti-SARS-CoV-2 advanced immunoglobulin drug “TAK-888” at the beginning of March, but with the cooperation of six companies to accelerate development and increase supply It is a big idea.
Regeneron has identified a number of antibodies to SARS-CoV-2 and plans to begin clinical trials of a cocktail of the two by early summer. Bill Biotechnology also identified two antibodies and licensed their rights in China to Wuxi Biologics in Shanghai. Bill is also developing an siRNA nucleic acid drug targeting SARS-CoV-2 in collaboration with Alnylam Pharmaceuticals of the United States. Absela Biologics, Inc. of the United States and Eli Lilly are jointly developing therapeutic and prophylactic antibodies.
Pfizer has identified protease inhibitor candidates with antiviral activity against SARS-CoV-2 and will begin clinical trials in the third quarter of this year.