Shionogi & Co., Ltd.
|Applicable indicator||Not applicable|
Shionogi is the smallest research-based pharmaceutical company in scope, with sales mostly in Japan. The company’s performance is lower compared to large research-based pharmaceutical companies in scope in Research & Development, Manufacturing & Production and Appropriate Access & Stewardship. The company’s R&D pipeline consists of 25 antimicrobial projects, of which 15 target priority pathogens. Shionogi discloses an environmental risk-management strategy, which is not applied to the company’s third-party suppliers of antibiotic APIs and drug products. The company provides no evidence of activities related to facilitating access. Shionogi’s commitment to stewardship is driven by engagement in a number of stewardship educational activities, as well as surveillance programmes in partnership with academic institutions in Japan. It does not remunerate sales staff based on sales volume of antibiotics.
Sales & operations
Shionogi is a large research-based pharmaceutical company headquartered in Japan. Its core therapeutic areas are infectious diseases and pain/central nervous system disorders, though its portfolio also covers additional areas, such as cardiovascular health and paediatrics. Within the infectious diseases area, the company is especially focused on three areas of research: severe bacterial and fungal infections, HIV/AIDS and viral respiratory infections and emerging/re-emerging infections. The company markets eight antimicrobial medicines in Japan, Taiwan and the US. During the fiscal year 2016, it sold approximately 15 million doses of antimicrobial medicines. In 2012, following a long-term collaboration on the development of several novel integrase inhibitors for the treatment of HIV/AIDS, Shionogi joined ViiV Healthcare, a joint venture originally established by GSK and Pfizer, solely focused on the development of HIV/AIDS medicines. Equity positions in ViiV Healthcare are GSK: 76.5%, Pfizer: 13.5% and Shionogi: 10%.
Shionogi markets eight antimicrobial medicines, two of which are listed on the WHO EML (Section 6). Six of the company’s antimicrobial medicines are antibiotics, including the combination sulfamethoxazole/trimethoprim (Baktar®), listed on the EML’s Access group. The remaining two medicines are antivirals: one indicated for influenza A/B infections and the other, dolutegravir (Tivicay®), indicated, in combination with other antiretroviral agents, for the treatment of HIV/AIDS. Dolutegravir was developed in collaboration with ViiV Healthcare and is listed on the WHO EML (Section 6).
Improve access to antimicrobial medicines. Shionogi can develop an access strategy for countries in scope,* that includes the filing of its newest antibiotics (including flomoxef (Flumarin®)), for registration. Currently, Shionogi has not filed its antibiotics for registration in countries in scope.*
Plan ahead for access and stewardship during R&D. Shionogi is developing one antibiotic candidate (cefiderocol) in late-stage clinical development. It is currently seeking partners to plan for its commercialisation, through licensing. Shionogi can ensure that these partnership agreements include access and stewardship provisions.
Ensure transparency on its approach to environmental risk management. Shionogi has stated a commitment to disclose its environmental risk-management strategy, the identities of its third-party suppliers and its external waste-treatment sites.
Expand environmental risk-management strategy. Shionogi can ensure its environmental risk-management strategy is applied to third parties who manufacture antibiotic APIs on its behalf, as well as to external waste-treatment sites. It currently has an environmental risk-management strategy that includes discharge limits, which are applied to its own manufacturing sites.
Continue developing early-stage projects. Shionogi has a large early-stage pipeline of R&D projects targeting priority pathogens. It can ensure that these early-stage projects move along the pipeline into clinical development.
Increase engagement in stewardship activities. Shionogi has engaged with academic institutes for several short-term surveillance programmes. It can ensure the development of long-term AMR surveillance programmes, and ensure that data is made publically available through open databases and collaboration with public health authorities.
A. Research & Development
25 projects, 15 target priority pathogens
A.1 Comparatively high antimicrobial R&D investments.
Shionogi reports that it invested more than USD 200 million in antimicrobial R&D in 2016, which is relatively high compared to other large research-based pharmaceutical companies in the Benchmark. The company’s antimicrobial R&D investments are almost as high as its revenues earned from antimicrobial medicines. These investments cover antimicrobial medicines only, as Shionogi is not involved in vaccine development.
A.2.1-2.2 Fifteen R&D projects in priority pathogen pipeline, one in clinical stage.
Shionogi has 25 antimicrobial R&D projects in its pipeline, two of which are in clinical stage development. Fifteen of the company’s projects target priority pathogens. It has an average- sized pipeline when comparing it to other large research-based pharmaceutical companies assessed by the Benchmark. Shionogi is the only company engaged in antifungal drug development. Its preclinical activities have a broad focus including bacteria, fungi, HIV and M. tuberculosis. Cefiderocol, a new cephalosporin, is its most advanced compound which is currently in Phase III clinical development. Shionogi is also developing an antibody against P. aeruginosa.
A.3 Some preclinical R&D projects being developed with public partners.
Shionogi is developing four preclinical projects in its priority pathogen pipeline through public- private partnerships. Three of these projects involve collaboration with universities, which are focused on the discovery of novel medicines that target HIV and multidrug-resistant gram-positive bacteria. The remaining project involves the screening of Shionogi’s compound libraries for candidates with activity against M. tuberculosis through the PDP with TB Alliance.
A.4 Stewardship commitment in place, but no information regarding access.
Shionogi reports that it has a stewardship commitment in place for its antibiotic candidate in late-stage development, but reports no information on access provisions. Shionogi commits to providing its investigational antibiotic (cefiderocol) only for indications for which limited or no alternative treatment options are available and where cefiderocol is likely to be an appropriate treatment option. This would include infections caused by, e.g., carbapenem-resistant and/or multidrug-resistant gram-negative pathogens. Shionogi plans to commercialise cefiderocol in the countries in which it has affiliate companies (the USA, China, Singapore, EU countries and Taiwan), and is currently in talks with partners to commercialise it outside of these countries. For this indicator, countries in scope are 106 low- and middle-income countries where access to medicine is likely limited. There is no information available on whether these countries are included in Shionogi’s commercialisation plans. It has signed the Davos Declaration, which includes a general commitment to ensuring access to antimicrobial medicines and vaccines, and to support the appropriate and responsible use of these products.
Pipeline targeting priority pathogens
B. Manufacturing & Production
B.1 Environmental risk-management strategy for own sites.
Shionogi has an environmental risk-management strategy to minimise the impact of antibiotic manufacturing discharge that includes auditing and discharge limits. The strategy currently applies to Shionogi’s own sites. Shionogi has committed to extending it, within a year, to its third-party manufacturers of antibiotic APIs and drug products. The company has made no statement about extending the strategy to external waste-treatment plants.
B.2 Commitment to increase transparency regarding environmental risk management.
Shionogi does not currently disclose its strategy to minimise the impact of manufacturing discharge of antibiotics. Notably, however, it has made a commitment to publish this strategy as well as the identities of its third-party manufacturers. It currently does not publish any elements looked for by the Benchmark, namely: antibiotic discharge levels, audit results, and the identities of its third-party manufacturers of antibiotic APIs and drug products, or of its external waste-treatment plants.
B.3 Commits to following GMP, including at 3rd-party sites.
Shionogi reports that it has mechanisms for maintaining a high quality of antibiotic production — namely following GMP standards. This commitment applies to its own manufacturing sites. Shionogi requires its third-party suppliers of drug products to apply the same quality standards to their production facilities.
C. Appropriate Access & Stewardship
C.1 Newest marketed antibiotics not filed for registration.
Shionogi reports that it has not filed its newest marketed antibiotics for registration in countries in scope.*
C.2-C.3 No marketed products in countries in scope.
Shionogi reports that it is not marketing any antimicrobials in any countries in scope.* Hence, in these countries, Shionogi does not report having equitable pricing approaches or processes in place to improve supply chain efficiency and prevent and/or respond to stock-outs.
C.4 Some involvement in AMR-related education.
Shionogi reports that it is involved in educational programmes for HCPs that include AMR stewardship, with conflict of interest (COI) mitigation measures in place. It has strategies in place for independent content development. Half of the programmes disclosed were delivered through courses, while the remaining programmes are delivered via web pages and leaflets.
C.5 Adopts appropriate promotion practices.
The Benchmark measures how companies address stewardship through appropriate promotion practices. Shionogi reports that it takes action in this regard: it reflects AMR trends in its marketing materials and does not remunerate its sales teams based on antibiotic sales volume.
C.6 No information regarding brochure and/ or packaging adaptations.
Shionogi does not provide sufficient information on any language, cultural or literacy adaptations made to its brochures or packaging that would promote appropriate use.
C.7 Surveillance programmes focused on Japan.
Shionogi has engaged with academic institutes for several short-term surveillance programmes. These programmes are aimed at measuring the current AMR landscape in different regions across Japan. All Shionogi’s studies will be published in peer-reviewed journals. After the period of analysis, the company reported engagement in further surveillance programmes in more countries, details of which are not available.
* Countries in scope are 106 low- and middle-income countries where access to medicine is likely limited
† EML Section 6: Anti-Infective Medicines
§ Net sales; FYE 31 March 2017
|| Net sales; FYE 31 March 2016