Global HealthPharmaceutical Regulations in Japan

Three Major Infectious Diseases and Neglected Tropical Diseases (NTDs)

Efforts to improve the healthy lives of over one billion patients in 149 countries and territories worldwide through new partnerships to break the vicious cycle that binds poverty and communicable diseases.

The majority of patients suffering from three major infectious diseases (HIV/AIDS, tuberculosis, and malaria) and Neglected Tropical Diseases (NTDs)* are concentrated in developing countries or among the poverty class. According to WHO, it is estimated that more than one billion people are affected worldwide. In particular, as communicable diseases continue to spread among the poverty class, the diseases themselves are doubling as a cause of poverty in numerous countries and territories. Breaking this vicious circle that binds poverty and communicable diseases is imperative in order to ensure both economic growths in developing countries and human security for all.

To overcome this global health issue, a number of various countermeasures are required, including reinforcing public health care systems, health insurance systems and other components of healthcare infrastructure in developing countries; establishing distribution systems to ensure that medicines and vaccines reach patients; and developing an environment for accelerating the development of new drugs and vaccines for patients suffering from communicable diseases. In turn, to promote those countermeasures, it is essential to realize flexible partnerships between the public sector and private sector-including participation by the pharmaceutical industry-as well as other forms of cooperation within the various stakeholders involved in improving public healthcare across the world.

* Neglected Tropical Diseases (NTDs)
NTDs are infections caused by parasites, bacteria and viruses that are mainly endemic in tropical areas of developing countries. It is estimated that over 1 billion people are affected worldwide with the 17 NTDs that WHO is currently focusing on. 17 focus diseases in the NTDs area The WHO is currently focused on treatments for the following NTDs Buruli ulcer, Chagas disease (American trypanosomiasis), cysticercosis, dengue/severe dengue, dracunculiasis (guinea-worm disease), echinococcosis, foodborne trematode infections, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil transmitted helminthiasis, trachoma, and endemic treponematoses (including yaws)

In Japan, public-private partnerships have gradually been established to take the initiative in resolving communicable diseases issues being faced by developing countries. In the past, national governments, UN organizations, charity organizations and other similar entities were the key providers of funding for research and development in the global health sector. In 2013, the Global Health Innovation Technology Fund(GHIT Fund), Japan's first global health focused public-private partnership was established. It is a very innovative approach which private sector is taking initiative and participating as funding partners. During five years after the establishment, the GHIT fund had obtained significant progress. As of June 2018, eight preclinical candidates have been identified in later phase of clinical trials including three projects targeting malaria, two projects targeting hepatitis, and three projects targeting NTDs.

The GHIT Fund is the world’s first product development fund for global health R&D. It is built on the strength of contributions from partners in the public, private, and civil sectors. Towards R&D and commercialization of pharmaceuticals, vaccines, and diagnostics which poorest of the poor in developing countries need, the GHIT Fund are investing in joint R&D projects of Japan and overseas related to the three major infectious diseases and NTDs. Companies participating in the GHIT Fund as a partner is as follows (As of June 2018).

Full Partners: Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Shionogi & Co., Ltd., Takeda Pharmaceutical Company Limited

Associate Partners: FUJIFILM Corporation, Otsuka Pharmaceutical Co., Ltd., Sysmex Corporation

Affiliate Partners: Glaxo Smith Kline K.K., Johnson & Johnson, Kyowa Hakko Kirin Co., Ltd., Merck Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd.

Through leveraging the advantages of new drug development based on our advanced science and technology to discover new drugs for infections in developing countries, the Japan Pharmaceutical Manufacturers Association seek to strengthen Japan's international contributions to global health.

Initiative by member companies
Provision of medicine to treat lymphatic filariasis free of charge In November 2010, Eisai agreed to provide 2.2 billion tablets of diethylcarbamazine (DEC), a medicine for treating lymphatic filariasis, to the World Health Organization (WHO) for free until the year 2020. Based on that agreement, Eisai used its factory in India to manufacture DEC tablets, and began providing them to countries where lymphatic filariasis is endemic in October 2013. In February 2016, a new public-private partnership has been initiated to provide diagnostic kits free of charge, for use in evaluating the success of mass drug administration (MDA) in LF elimination and helping to determine when MDA can stop. Eisai is also taking part in the partnership. Through the supply of DEC tablets and diagnostic kits, Eisai is contributing to the global program to eliminate lymphatic filariasis.
Development of medicine for treating HIV infections Over time, Shionogi and ViiV Healthcare have engaged in the joint research and development of dolutegravir, a new HIV integrase inhibitor. Starting in December 2012, ViiV Healthcare submitted New Drug Applications (NDAs) in the United States, Europe, Japan and other regions to have dolutegravir approved as a new drug. As of today, the drug has been made available for sale globally under the product name "Tivicay®.
Triumeq®, combines dolutegravir, an integrase inhibitor, with the nucleoside reverse transcriptase inhibitors abacavir and lamivudine, was approved for the indication of HIV infection in August 2014 in the US and in September 2014 in Europe, and is also being sold globally.Juluca® (dolutegravir and rilpivirine) approved as first 2-drug regimen, once-daily, single pill - a complete regimen for the maintenance treatment of virologically suppressed HIV-1 infection in the US on November 21st 2017
Development of medicine for treating tuberculosis

For over 30 years, Otsuka Pharmaceutical has engaged in the research and development of drugs with the aim of contributing to the eradication of tuberculosis. Delamanid, a novel drug discovered by Otsuka that targets multidrug-resistant pulmonary tuberculosis was developed through clinical trials in nine countries with approximately 500 patients. It first received regulatory approval in the EU, Japan and Korea in 2014 and is currently available to patients in over 70 countries.

In addition, phase Ⅰ trials have commenced for OPC-167832, an Otsuka-discovered compound with a completely different mechanism of action than delamanid’s.

Development of medicine for treating dengue fever Takeda Pharmaceutical is engaged in the development of vaccines for dengue fever. "DENVax" a tetravalent vaccine that covers all four virus forms causing dengue fever, is currently undergoing Phase Ⅲ testing.
Development of medicine for treating Chagas disease Eisai is collaborating with the Sabin Vaccine Institute (Sabin), the Baylor College of Medicine and Aeras to develop a vaccine for Chagas disease. This research was originated from a jointly initiated collaboration research of Eisai and Sabin with the aim of developing a new vaccine for Chagas Disease and Leishmaniasis that utilizes Eisai's in-house discovered selective TLR4 agonist, E6020, as a novel adjuvant (a substance that enhances immune effects).
Development of medicine for treating malaria Takeda Pharmaceutical engages in joint research and development with the Medicines for Malaria Venture (MMV) for the development of the antimalarial drug DSM265 and the formulation of ELQ-300.
DSM265 currently exhibits a favorable safety profile in Phase Ⅰ clinical testing.
Expectations are being placed on ELQ-300 as a next-generation drug that will enable the prevention and treatment of malaria in small doses. The drug is currently in the clinical testing phase.
Development of pediatric formulation for schistosomiasis Astellas engages in the development of a pediatric formulation of praziquantel for the treatment of Schistosomiasis in a consortium with Merck KGaA, Lygature, Swiss Tropical and Public Health Institute (Swiss TPH), Farmanguinhos, Schistosomiasis Control Initiative (SCI), Kenya Medical Research Institute (KEMRI), and Université Félix Houphouët-Boigny (UFHB). Astellas developed the pediatric formulation by using its own drug formulation technology and transferred it to Farmanguinhos and Merck KGaA. The consortium is conducting Phase Ⅱ clinical trials. Astellas continues to provide its know-how and technology to the consortium in clinical development following formulation development.
Joint research and development of medicine for treating and vaccines for malaria and NTDs Eisai is engaged in a comprehensive joint research and development agreement with The Oswaldo Cruz Foundation in Brazil for medicine to treat and vaccines for malaria and NTDs. For their initial project, these two entities commenced joint research and development of E6446, an active TLR9 antagonist, and analogous compounds as forms of medicine for treating cerebral malaria.
Participation in "WIPO Research Consortium" for developing medicine for treating tropical diseases

As a member of the "WIPO Research Consortium," an international joint venture organized by the World Intellectual Property Organization (WIPO) for developing medicine for treating tropical diseases, Eisai supplies information on seven compounds to a publicly-available database. The intellectual property registered in this database is provided free of royalties for use in the development of medicine for treating tropical diseases as well as the eventual sale of products in developing countries that adopt those drugs at a later date.

Takeda joined WIPO Re:Search, a consortium in 2016 to accelerate research and development (R&D) of new drugs, vaccines, and diagnostics for neglected tropical diseases, malaria and tuberculosis. Takeda and the National Institute of Allergy and Infectious Diseases (NIAID) will examine the feasibility of using Takeda’s microneedle patch technology to administer a protein antigen-based, transmission-blocking malaria vaccine developed by the NIAID’s Laboratory of Malaria Immunology and Vaccinology (LMIV).

Development of vaccine for treating Chagas disease and Leishmaniasis Eisai is collaborating with the Sabin Vaccine Institute (Sabin), the Baylor College of Medicine and Aeras to develop a vaccine for Chagas disease. This research was originated from a jointly initiated collaboration research of Eisai and Sabin with the aim of developing a new vaccine for Chagas Disease and Leishmaniasis that utilizes Eisai's in-house discovered selective TLR4 agonist, E6020, as a novel adjuvant (a substance that enhances immune effects).
Participation in global partnerships for developing tuberculosis drugs Eisai participates in the "Tuberculosis Drug Accelerator" ("TBDA"), a partnership that aims to conduct revolutionary drug discovery for tuberculosis. Jointly established by seven global pharmaceutical enterprises and six research institutions and endorsed by the Bill & Melinda Gates Foundation, TBDA seeks to develop new medicines with the potential to fully treat tuberculosis with a one-month dose relative to the six months currently required by existing methods of treatment.
Joint research and development for developing new drugs for tuberculosis and NTDs Eisai is engaged in joint research for the development of new drugs for Neglected Tropical Diseases ("NTDs") and tuberculosis with the Broad Institute, a joint research facility under Harvard University and the Massachusetts Institute of Technology.
Screening programs for containing infections in developing countries (GHIT Fund programs)
  • Eisai is part of a GHIT Fund-sponsored program to screen for candidate compounds for treating malaria, leishmaniasis and Chagas disease.
  • Shionogi is also engaged in a GHIT Fund-sponsored programs for searching out drug candidates for treating leishmaniasis and Chagas disease.
  • Takeda Pharmaceuticals is part of a GHIT Fund-sponsored program for searching out candidate drugs for treating tuberculosis, malaria, leishmaniasis, and Chagas disease.
  • Sumitomo Dainippon Pharma is part of a GHIT Fund-sponsored program for searching out drugs for treating malaria.
  • Kyowa Hakko Kirin is participating as an Affiliate Partner and continues to support the GHIT Fund.
  • Mitsubishi Tanabe Pharma is part of a GHIT Fund-sponsored program for searching out candidate drugs for treating tuberculosis and malaria.
  • Astellas engages in GHIT Fund-sponsored screening programs to find drug candidates for the treatment of tuberculosis and malaria. Astellas provides its original library of compounds in the programs. Astellas also engages in a GHIT Fund-sponsored Hit-to-Lead program to find lead compounds for the treatment of NTDs (leishmaniasis and Chagas disease). Astellas provides its original library of compounds in the program.
Participation in London Declaration on Neglected Tropical Diseases Eisai has established international public-private partnerships with twelve major global pharmaceutical corporations, the Bill & Melinda Gates Foundation, the World Health Organization (WHO), the governments of the United States and the United Kingdom, the World Bank and governments of countries where NTDs are endemic, and issued the joint "London Declaration" to collectively fight to contain ten NTDs by 2020.
Development of medicine for treating eumycetome Eisai and the Drugs for Neglected Diseases initiative signed an agreement to proceed with clinical development of Eisai's anti-fungal drug E1224 (fosravuconazole) for the treatment of eumycetoma, a fungal form of mycetoma, one of the world's most neglected diseases. E1224 will be investigated in a clinical trial in collaboration with the Mycetoma Research Center (MRC) of the University of Khartoum, Sudan. Mycetoma was designated as a new NTD and added to WHO's list of NTDs in 2016.
New Drug Series to be Developed for “Ideal Treatment” for Visceral Leishmaniasis DNDi and Takeda will collaborate on a “lead optimization program” of the aminopyrazole series, with the ultimate goal of identifying the best compound to treat VL, which will then move on to further preclinical development. They’ll continue designing and making improved candidates based on the early aminopyrazoles, select the most promising 4-6 leads, then paring them down to 2-3, and then eventually one that best meets the goals for a new, more effective drug.
Development of medicine for treating malaria Eisai entered into a joint research agreement with St. Jude Children's Research Hospital and Medicines for Malaria Venture to develop a new antimalarial medicine. This partnership aims to develop a new medicine that will be rapidly effective, cure in a single dose and provide lasting protection against reinfection. A Phase I clinical study was initiated at St. Jude Children's Research Hospital.
Development of medicine for treating malaria Eisai joined a research program with the Liverpool School of Tropical Medicine and the University of Liverpool to develop E209, a new antimalarial. E209 is expected to be effective in patients for whom artemisinin-based malaria treatments are ineffective due to resistance.
Development of medicine for treating malaria Eisai is conducting exploratory research to find compounds that can selectively inhibit the function of GWT-1, a malaria drug target protein identified at Eisai. Compounds are being further assessed through a collaboration with Medicines for Malaria Venture.
Development of medicine for treating Filariasis Eisai commenced research in collaboration with the Liverpool School of Tropical Medicine and the University of Liverpool to jointly identify new drugs effective against lymphatic filariasis and onchocerciasis (river blindness), both major types of filariasis. The goal is to develop a treatment that can effectively eradicate the worms that cause filariasis by first eliminating theWolbachia bacteria inside them which the worms (filariae) depend upon for growth, development and survival.
Development of new medicine for treating tuberculosis To create an innovative new drug for tuberculosis, one of the top 3 major infectious diseases worldwide, is Shionogi’s mission. Shionogi discovered S-004992 as a drug candidate in C&O, the subsidiary in China, and will initiate FTIH study in 2018 in China

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