Reviving the pharmaceutical industry: “Late drug discovery”

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Second in a series

“Nobody called me when I published the article, but I thought messenger RNA (mRNA) would be a great medical treatment.”

These were the words of Katalin Kariko, a specially appointed professor at the University of Pennsylvania, on April 15 in Tokyo. She was attending a press conference of the winners of the Japan Prize, which is awarded to scientists who have made a significant contribution to society.

Kariko is the creator of the mRNA vaccine, which was first used during the COVID-19 pandemic and quickly became the global vaccine of choice.

The vaccine is made up of mRNA which contains the genetic information that the virus uses to spread, and it creates these viral proteins inside the body. By doing this, antibodies are induced and immunity is built.

Compared to other forms of vaccines, it is easier to synthesize artificially and it is possible to mass-produce it in a short time. It has also been shown to have an effect on reducing symptoms as well.

Ensure the security

The main players in the development of the vaccine were the German BioNTech and the American Moderna. BioNTech, which jointly developed the vaccine with US company Pfizer, was founded in 2008. Moderna was founded in 2010.

In other words, both companies can be considered part of the technologically competent “Gen Z”. Dr. Kariko is also Senior Vice President at BioNTech.

Research into using mRNA vaccines to treat cancer and heart failure is also advancing rapidly. Technology is revolutionizing the world of medicine and Dr. Kariko is a serious candidate for the Nobel Prize.

At center stage are Gen Z pharma companies.

Artificially created mRNA can cause the immune system to produce severe inflammatory effects when it enters the body, which has long been a barrier to clinical use. Kariko and others found that minor structural changes could stave off these immune system attacks and published the results in a paper in 2005. However, little attention was paid to it at first.

The situation changed after 2010s. The technique of enclosing mRNA in lipid capsules and transporting it to cells was established and the efficiency improved significantly.

Moderna and BioNTech have accelerated their research and development efforts, and the driving force has been the support provided by government funding. The underlying principle has been the sense of crisis that “countermeasures against pandemics ensure the very security of the country”.

Science with an ethical sense of duty

The development of vaccines against infectious diseases would be unprofitable. Even after large investments, once the disease stops spreading, the demand disappears. There is also a risk of not making a profit. For this reason, in addition to the effort of private companies, government support is crucial.

Moderna alone, which grew with support from the US Department of Defense and others, received US$100 million (approximately ¥13 billion) in funding from the US government between 2013 and 2016. On the other hand, the budget allocated by the Japanese Agency for Medical Research and Development (AMED) for the entire “Emerging and Re-emerging Infectious Disease Management Project” for the 5-year period from 2015 is only ¥4.1 billion to ¥6.6 billion JPY (US$30-48 million) per year.

“It’s not a profit motive. We developed mRNA vaccines guided by an ethical sense of duty,” says Dr. Kariko.

With the myopic ministry, Japan missed something

In the mid-2010s, Japan was also developing its own mRNA vaccine. It was a public project that Dr. Ken Ishii (currently a professor at the University of Tokyo Institute of Medical Sciences), who was then at a national research institute, worked on with Daiichi Sankyo. Dr. Ishii also served as referee for Dr. Kariko’s 2005 paper.

“At the time, Moderna and BioNTech were accumulating large amounts of funding and attracting the most outstanding researchers with high salaries. By comparison, vaccines were considered ‘old business’ in Japan, and the climate was not conducive to innovation,” he said.

However, the country began to act in 2015, when Dr Ishii advocated the importance of vaccines in response to the outbreak of Middle East Respiratory Syndrome (MERS) in South Korea.

The Japanese government allocated 36 million yen (262,000 USD) in 2016 and 60 million yen (436,000 USD) in 2018. The research was promising and good data was obtained through animal experiments.

However, when a budget of ¥400 million JPY (3 million USD) was requested to cover the costs of preparing for clinical trials, it was reduced to ¥10 million JPY (73,000 USD). “MERS has taken hold, how about asking private companies? officials responded curtly.

“Dare to invest in new technology, that courage and bravery has disappeared in Japan,” Dr. Ishii said in frustration.

“The development of human capital is an urgent task”

COVID-19 spread rapidly after the first person was infected in Wuhan Province, China in December 2019, and the world was caught in a pandemic.

The United States launched “Operation Warp Speed” and invested about US$10 billion (about ¥1.3 trillion yen) in vaccine development. Moderna and other companies have received this funding.

The company and BioNtech-Pfizer took advantage of research accumulated during the pre-pandemic period to secure emergency approval for the vaccine just a year after the outbreak.

Also in Japan, Daiichi Sankyo began developing an mRA vaccine and completed plans along with other overseas groups. However, the know-how to really relate this to a practical application was lacking, and there was no foundation to disseminate it in society.

In the end, Japan had to rely on foreign-made vaccines to protect citizens.

“The COVID-19 pandemic has caused a paradigm shift of a level that only happens once in a hundred years. Developing systems to train and secure human capital is an urgent task,” said Tooru Tanzawa of Daiichi Sankyo, Director of Vaccine Planning Department. He added:

“Using the industry foundation, we need to build a strong foundation for business, government and academia to produce something that can be used around the world. Now is the time.”

Will it be possible for Japan to regain its place as a pharmaceutical innovator? This series explores challenges and pathways through the lens of vaccines.

Next: Mistrust of vaccines and their development

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(Read the article in Japanese on this link.)

Author: The Sankei Shimbun

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