HEALTH & WELFARE

RESEARCH THAT SAVES US FROM
INFECTIOUS DISEASES:

FIGHTING TB
THROUGHOUT THE WORLD

Tuberculosis is counted as one of the major infectious diseases threatening global health.
A drug developed by a Japanese pharmaceutical company constitutes the first effective new anti-TB drugin about 40 years, paving the way to help conquer the disease completely.

On World TB Day, March 24, 2017, Otsuka Pharmaceutical, in cooperation with South Africa’s Ministry of Health and a non-governmental organization, launched
an access program for delamanid (trade name Deltyba) that is still in progress. The top right image shows one of the first patients to have received the drug.

Tuberculosis (TB), which spread profusely
in the countries of Western Europe during theindustrial revolution, was once a threat to the entire
world. However, from the 19th century onwards,
improvements in living standards and healthcare led
to a decline in the number of persons afflicted withthe disease. Now, TB is considered by people in thosecountries to be a disease of the past. That assumption,
however, is incorrect. According to the Global
TB Report 2020, an estimated 2 billion people are

infected with the bacteria that causes TB worldwide.
Even now, 1.4 million people die from the diseaseeach year, making it one of the top 10 causes of deathin the world. In fact, outbreaks sporadically occur
not only in developing countries, but in Westerncountries as well.
Exacerbating the problem in recent years has been
the appearance of multidrug-resistant tuberculosis(MDR-TB) strains that show resistance to existing
TB drugs. At the Kyushu-Okinawa Summit in 2000,

Japan made combating infectious diseases, including
TB, one of the summit’s major agenda topics. Driven
by Japanese initiatives to tackle infectious diseases,
the Global Fund to Fight AIDS, Tuberculosis,and Malaria was formed in 2002. Amid renewed
awareness of TB as a global health problem, an antiTB drug developed by a Japanese pharmaceuticalcompany is offering new hope. The drug in question
is delamanid, which was developed by Otsuka
Pharmaceutical Co., Ltd., and received regulatory
approval in the EU and Japan in 2014. As the firstnew anti-TB drug in about 40 years, it is proving
to be effective against resistant strains and its use isincreasing throughout the world.
When a standard treatment for TB was establishedin the 1970s, the development of anti-TB drugs
came to a standstill around the world, but Otsuka
Pharmaceutical continued its development. “Patients
must receive TB treatment over a much longer timecompared with other infectious diseases. In quite afew cases, treatment is halted because the side effects
are too severe, and without administering continuous
treatment, its elimination becomes difficult. We
believed that this was a therapeutic field that showed
the promise of improvement from a quality-of-life
perspective as well,” says KAWASAKI Masanori,
Global TB Project leader. “If no one else was going to
do it, we felt that we must continue the research, andthat ultimately led to the development of delamanid.”
Rather than being administered by injection
or drip, delamanid is taken orally. That is a hugeadvantage because oral medicine is much easier forpatients to manage versus injectable drugs. Anotherbenefit of delamanid is that there are few druginteractions with the treatments for HIV/AIDS
or diabetes, meaning it could also be effective forpatients with coexisting medical conditions.
After earning its first approval in Europe in 2014,
delamanid has since been approved in 15 countries,including South Africa and India. In the RussianFederation, the major pharmaceutical company
R-Pharm was granted licensing rights in 2017 as partof the Eight-Point Cooperation Plan. Furthermore,
as of the end of 2019, the use of delamanid is now
possible in over 100 countries, thanks to an agreementin 2016 between Otsuka Pharmaceutical and theWhen Otsuka Pharmaceutical began drug discovery in 1971, it selected TB as one of its
first research themes. Its untiring research efforts yielded fruit, realizing innovation thathas spurred new drug development.

Stop TB Partnership, an organization established incollaboration with WHO and other partners.
The development of a drug to defeat bacteria thatcause TB strains, which are difficult for antibiotics
to act on, was not easy. The development team at
Otsuka Pharmaceutical was exhaustively selective
when deciding which candidate compounds tochoose as the starting point of the drug discovery
process. Through repeated trial and error, such asadopting unorthodox drug synthesis methods, theteam finally achieved its goal.
Presently, the team is developing a next-generation
drug candidate that will work by a different
mechanism of action from delamanid. In February
2020, Otsuka Pharmaceutical joined hands with theBill & Melinda Gates Foundation, Gates Medical
Research Institute, Johnson & Johnson, Evotec SE,and GlaxoSmithKline plc, to set up the “PAN-TB
collaboration,” a consortium established to accelerate
new treatments for TB on a global scale. The company
is providing its knowledge gained so far through TBresearch. Assuring us that his team will continue todirect their efforts toward fighting TB, Kawasaki
says, “As demonstrated by the novel coronavirus
crisis, it is important that all countries cooperate intreating infectious diseases as a global issue. As partof that, our mission is to create an environment wheretreatment can be administered to patients easily andmore effectively.” 

Left: Otsuka Pharmaceutical is cooperating on a project to improve TB treatment indeveloping countries. In Indonesia, it is working with a local university to support theevaluation of treatment for TB and MDR-TB.
Right: The Global TB Project, driven by Otsuka Pharmaceutical, is comprised of members
from various countries (photo taken at the Princeton office in the United States).