BY OSAMU TSUKIMORI, STAFF WRITER

Over two years since the emergence of COVID-19, Japan’s pharmaceutical companies are finally in the home stretch of introducing their vaccines in the country, a move that experts say will be extremely important from the perspective of self-reliance.

In an important step, Mitsubishi Tanabe Pharma Corp. group became the first Japanese company to receive approval for its COVID-19 vaccine, in Canada, late last month. It is considering applying for approval in Japan between July and September.

Pfizer Inc. and Moderna Inc. developed their vaccines at unprecedented speeds thanks to billions of dollars provided by the U.S. government. But the Japanese government’s investment in and support for homegrown vaccines paled in comparison, and the country was ill prepared for a sudden health crisis like the pandemic, as it had insufficient research and development capabilities and technological infrastructure, industry sources say.

In spite of the lower government funding, some Japanese companies have been making steady progress.

The development of domestic vaccines will mark an important milestone for Japan, as their availability will mean the country no longer has to rely on foreign manufacturers’ vaccines, said Dr. Tetsuo Nakayama, a professor at Kitasato Institute for Life Sciences and director of the Japanese Society of Clinical Virology.

To get their vaccines to market more quickly, Japanese pharmaceutical companies are considering using a fast-track approval system for emergency situations that obtained Cabinet approval this month. A randomized, double-blind, placebo-controlled trial involving 30,000 volunteers is considered to be preferable when it comes to evaluating vaccines, but the creation of highly effective COVID-19 shots has raised ethical questions about conducting such time-consuming trials, as participants would be passing up opportunities to get vaccinated with other, already approved shots during the trial.

A revised bill pertaining to the Pharmaceutical and Medical Device Act under discussion in parliament would pave the way for the time-limited authorization of new drugs and vaccines if their efficacy is “presumed” even before the final stage clinical trial is finished, with rigorous safety checks remaining in place. The approval requires that it is an emergency situation and there’s no alternative in Japan that can satisfy the medical need in question. The health ministry is considering giving two-year emergency approvals and canceling them if efficacy cannot be confirmed during that time.

Companies may take advantage of immune system biomarkers to predict the protection given by a vaccine, Nakayama said. If clinical trials show that a vaccine candidate is not inferior to Pfizer’s vaccine in boosting neutralizing antibodies, for example, Japanese companies could file an application for approval under the fast-track approval system.

“They would have to meet the (current) standard,” Nakayama said. “If it’s inferior to the approved vaccines, then we don’t need to use it. The antibodies generated by Pfizer and Moderna’s vaccines are prone to falling significantly over time, so how the antibodies generated by Japanese companies’ vaccines fare over time will be compared as part of a follow-up.”

Here is a rundown of each vaccine candidate under development:

Shionogi & Co.

The company is aiming to start the commercial supply of its recombinant protein-based vaccine candidate as early as May. Similar performance to the Pfizer booster in increasing neutralizing antibodies was observed for Shionogi’s shot when it was administered as a third dose at least six months after a person received the Pfizer vaccine, the company found in its interim analysis of an additional late stage trial involving 206 adults.

In terms of safety, the trial found that there were no serious adverse side effects in either of its test groups — those who received Shionogi’s vaccine and those who received Pfizer’s — but Shionogi’s subjects had a slightly lower number of people who experienced mild side effects such as fever, headache, fatigue, muscle ache or pain around the injection site.

Shionogi President Isao Teshirogi has said that the company expects to achieve a production capacity of at least 60 million doses per year by the end of 2022.

Medicago Inc.

The Quebec-headquartered biotech company, which is about 79% owned by Mitsubishi Tanabe Pharma, is developing a plant-based “virus-like particle” (VLP) vaccine, which it aims to commercialize in Japan in the fiscal year starting in April. The shot’s approval in Canada marked the first time that a plant-based vaccine for humans had received formal authorization anywhere in the world, a Mitsubishi Tanabe Pharma spokeswoman said.

The VLP has viral proteins that can elicit a strong immune response, but it cannot infect the host or replicate itself because it contains no genetic information.

The company says a late-stage clinical trial showed that its vaccine has an efficacy of 75.3% and 88.6% against the delta and gamma variants, respectively. The company plans to submit the clinical data used for approval in Canada, as well as data from another trial in Japan, when it files for approval in the latter country.

Canada’s drug regulator has approved the vaccine for use in people age 18 to 64. Medicago has a contract to allocate up to 76 million shots to the Canadian government, of which it is set to supply up to 20 million this year.

Daiichi Sankyo Co.

The company has been developing a messenger RNA vaccine, the same type of shot as those developed by Pfizer and Moderna. The company began a clinical trial in January to evaluate its effectiveness as a booster shot and is aiming to commercialize the vaccine this year.

The mRNA vaccines instruct cells to make a spike protein like those found on the surface of the coronavirus, which the immune system recognizes and makes antibodies against.

Daiichi Sankyo says it uses a proprietary delivery technology that is expected to raise the safety and efficacy of the vaccine.

KM Biologics Co.

The Meiji Holdings Co. unit is developing an inactivated vaccine, a type of shot in which a neutralized pathogen induces an immune response without causing the severe symptoms of the disease. Currently, inactivated vaccines and live attenuated vaccines, which use a weakened pathogen, make up the majority of the vaccines in use today. China has already authorized an inactivated COVID-19 vaccine developed by Sinovac Biotech Ltd.

KM Biologics is aiming for commercialization this year, and the nature of the shot could help with its adoption in Japan.

“KM Biologics’ vaccine has the potential to be used in children because it’s the same type as the vaccines for Japanese encephalitis and other diseases, which can be used from the age of 3,” Nakayama said.