As well as being more than a year behind global rivals in developing COVID-19 vaccines, Japanese drugmakers are scrambling to catch up with international competitors in their search for brand new medicines for the disease, highlighting the country’s uphill battle toward gaining the upper hand over the pandemic.
In November, the U.S. Food and Drug Administration granted emergency use authorization to antibody therapy bamlanivimab, developed by an American drugmaker Eli Lilly, marking the world’s first approval of a new drug specifically developed to treat COVID-19. The same month, the FDA also gave the green light to an antibody treatment developed by U.S. biotech firm Regeneron Pharmaceuticals Inc.
South Korea also granted emergency authorization last month to a domestically made antibody treatment developed by Celltrion Healthcare Co., a move local media touted as the world’s third COVID-19 antibody treatment confirmed by regulators.
In Japan, however, no applications for medicine specifically tailored to COVID-19 have been filed yet, as domestic pharmaceutical companies have not invested heavily enough in biomedicine development amid uncertainties over expected returns on investment. In addition, there’s little academic-industry collaboration whereby university research is transferred to biotech and pharmaceutical companies for developing drugs.
Instead, the country has approved two existing drugs designed for treating other diseases. Last May, Japan authorized the use of Gilead Sciences Inc.’s antiviral drug remdesivir, originally developed as a medication for the Ebola virus, followed by approval of steroid drug dexamethasone two months later.
The idea of repurposing old medication, called “drug repositioning,” is not new, and it can deliver drugs to patients sooner. The practice has also become more common in recent years, as existing drugs have already been shown to be safe for use in humans and so drugmakers can save a significant amount of money by avoiding the need for preclinical animal studies.
Besides the two government-approved medications for treating moderate to severe cases of COVID-19, the treatment guideline of the Japanese Association for Infectious Diseases lists several other options, as the country still lacks key medicines to treat patients with mild to moderate symptoms.
One of them is anti-influenza drug Avigan. The medicine, also known by its generic name favipiravir, did not receive regulatory approval in December because clinical data showing a shortened recovery time for patients was deemed to be insufficient, as the trial was conducted on a “single-blind” basis, meaning the doctors knew that the recipients were receiving Avigan or a placebo. Fujifilm Holdings Corp., the drug’s developer, is reportedly set to conduct an additional clinical trial as early as April to have another shot at winning regulatory approval.
Despite the setback, Avigan has been widely used in Japan as one of the first treatments for hospitalized patients to inhibit the replication of the virus in cells, says Dr. Tetsuo Nakayama, a project professor at Kitasato Institute for Life Sciences and director of the Japanese Society of Clinical Virology.
“While the protocol for treating patients with severe symptoms with remdesivir and dexamethasone is in place, no comparable system has been set for treating those with mild to moderate symptoms, as health care workers are casting around for which optimum medication to prescribe for these symptoms,” Nakayama said.
Other drugs proposed by the Japanese Association for Infectious Diseases include anti-inflammatory drug baricitinib, used to treat rheumatoid arthritis, and Chugai Pharmaceutical’s antibody treatment tocilizumab. Clinical trials have shown that the latter, marketed as Actemra, can reduce the risk of death in severe cases of COVID-19 by helping prevent a cytokine storm, a life-threatening overreaction of the body’s immune system.
Despite a lack of approval for new COVID-19 drugs, several efforts are ongoing. A “hyperimmune globulin” medicine developed by a global alliance including Takeda Pharmaceutical Co. is seen as a front-runner. A late-stage clinical trial involving about 500 patients has been under way globally since late last year to evaluate whether the therapy, which is derived from plasma collected from recovered COVID-19 patients, prevents further progression of the disease.
The Tokyo-based National Center for Global Health and Medicine has been leading a clinical trial on the globulin medication involving 10 patients in Japan in cooperation with Fujita Health University in Aichi Prefecture, with funding from the U.S. National Institute of Allergy and Infectious Diseases.
Globally, there’s a race to develop new drugs using antibodies. Shimane University and Nagasaki University researchers have developed five artificially made neutralizing antibodies that would disrupt the coronavirus’s ability to infect human cells. The team applied for a patent in January and is aiming to develop a new drug in the future.
“By further creating new antibodies, it’s possible to respond to the new variants of the novel coronavirus,” Takeshi Urano, professor at Shimane University’s Faculty of Medicine, said.
The Kitasato Institute has been conducting a clinical trial for ivermectin, a drug used to treat parasitic diseases, to evaluate the efficacy of the drug. The drug was discovered by Kitasato University’s distinguished emeritus professor Satoshi Omura, a Nobel Prize winner. While there is conflicting clinical trial evidence on the efficacy of the drug, Haruo Ozaki, president of the Tokyo Medical Association, has proposed the emergency use of the treatment for patients recuperating at home to prevent serious complications from the disease.
Although overseas firms have succeeded in developing COVID-19 vaccines that have been shown to be highly effective in less than a year, the development of promising drugs takes much longer, Nakayama said.
“The usual method of screening various materials in the chemical compound library to evaluate whether it would inhibit the amplification of the novel coronavirus is a painstaking process that takes a significant amount of time with very low chance of success,” he said.
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