First independent framework for assessing pharmaceutical company action Antimicrobial Resistance Benchmark 2020 Antimicrobial Resistance Benchmark 2020 ACKNOWLEDGEMENTS The Access to Medicine Foundation would like to thank the following people and organisations for their contributions to this report.1 FUNDERS The Antimicrobial Resistance Benchmark research programme is made possible with financial support from UK AID and the Dutch Ministry of Health, Welfare and Sport. Expert Review Committee Research Team Reviewers Hans Hogerzeil - Chair Gabrielle Breugelmans Christine Årdal Gregory Frank Fatema Rafiqi Karen Gallant Nina Grundmann Adrián Alonso Ruiz Hans Hogerzeil Magdalena Kettis Ruth Baron Hitesh Hurkchand Joakim Larsson Dulce Calçada Joakim Larsson Marc Mendelson Moska Hellamand Marc Mendelson Margareth Ndomondo-Sigonda Kevin Outterson Katarina Nedog Sarah Paulin (Observer) Editorial Team Andrew Singer Anna Massey Deirdre Cogan ACCESS TO MEDICINE FOUNDATION Rachel Jones The Access to Medicine Foundation is an independent Emma Ross non-profit organisation based in the Netherlands. It aims to advance access to medicine in low- and middle-income Additional contributors countries by stimulating and guiding the pharmaceutical Thomas Collin-Lefebvre industry to play a greater role in improving access to Alex Kong medicine. Nestor Papanikolaou Address Contact Naritaweg 227-A For more information about this publication, please contact 1043 CB, Amsterdam Jayasree K. Iyer, Executive Director The Netherlands [email protected] +31 (0) 20 215 35 35 www.amrbenchmark.org 1 This acknowledgement is not intended to imply that the individuals and institutions referred to above endorse About the cover: Young woman from the Antimicrobial Resistance Benchmark methodology, Brazil, where 40%-60% of infections are analyses or results. Decisions regarding the final anal- caused by drug-resistant bacteria. ysis were ultimately made by the Access to Medicine Foundation. Photo: FG Trade (Getty Images) 2 Access to Medicine Foundation The fragile antibiotic market has reached a tipping point The Antimicrobial Resistance Benchmark has evaluated for This second Benchmark provides a reality check. the second time how the most important players in the anti- Fixing the problem does not require a scientific miracle. It biotic market are addressing the rise of resistance and the demands a very human solution – albeit one that is easier said global need for appropriate access to antibiotics. Although we than done. The tough market conditions must be replaced can see progress — it’s hanging by a thread. through a mix of public and private investment to ensure a We have reached a tipping point where large and prom- healthy ecosystem of pharmaceutical innovation, production inent drugmakers have retreated from the antibiotics field and supply. and smaller innovative biotech companies have gone bank- We see good practice in multiple areas in 2020. More com- rupt due to the poor financial rewards on offer. Antibiotics are panies are stepping up – with promising ideas for tackling the taken for short courses and the most precious products are toughest pathogens, and improvements in tracking resistance reserved for emergencies. Only a handful of large research- and safeguarding the effectiveness of existing products. We based companies remain broadly engaged in developing new can’t take their commitment for granted and wait for more antibiotics, down from more than 20 in the 1980s. Losing any companies to abandon this vital area of modern medicine. It is more big suppliers and innovators will make it extremely hard not too late to prevent irreparable damage to the global sup- to ramp up effective drug discovery and development oper- ply of antibiotic medicines and vaccines. ations, while the tough economics of the market discourage investment in new manufacturing capacity. This disinvestment and industry consolidation has created an increasingly fragile manufacturing and supply chain. While the top 30 companies have more than 200 sites for produc- ing antibiotics globally, just four companies – GSK, Novartis (through its generics arm, Sandoz), Teva and Mylan – account for more than half of them. Each year, more than 90 billion packs of medicines are used worldwide to treat infections. Antimicrobial resistance is not a future problem. Jayasree K. Iyer The impact of drug resistance is already being felt today. Executive Director Antibiotic resistance causes more than 500,000 deaths each Access to Medicine Foundation year, including more than 200,000 infant deaths. In India, for example, resistance exceeds 70% for many widespread bac- teria. Most at risk are patients living in the poorest countries, where medicine choices are limited. 3 Antimicrobial Resistance Benchmark 2020 Table of contents 6 EXECUTIVE SUMMARY 91 BEST PRACTICES 92 Research & Development 12 BENCHMARK PERFORMANCE 94 Access & Stewardship - Access 12 Antimicrobial Resistance Benchmark - 2020 95 Access & Stewardship - Stewardship 14 How large research-based pharmaceutical companies perform 97 REPORT CARDS 16 How generic medicine manufacturers perform 98 Abbott Laboratories 18 How small and medium-sized enterprises perform 101 Achaogen Inc 104 Alkem Laboratories Ltd 20 KEY FINDINGS 107 Amplyx Pharmaceuticals Inc 20 R&D: Signs of movement in access and stewardship 109 Aurobindo Pharma Ltd planning in R&D, from a low base 112 Cidara Therapeutics 22 Access: Pharma companies are missing opportunities 114 Cipla Ltd to make antibiotics available 117 Debiopharm 24 Stewardship: Progress in how pharma companies 119 Entasis Therapeutics Inc tackle overselling antimicrobials 122 Fresenius Kabi AG 26 Surveillance: Pfizer is the first company to share raw 125 GlaxoSmithKline plc data on the spread of resistance 129 Hainan Hailing Chemipharma Corporation Ltd 132 Johnson & Johnson 28 PIPELINE & PORTFOLIO ANALYSIS 136 Melinta Therapeutics Inc 28 R&D Pipelines: Which companies are developing new 139 Merck & Co, Inc treatments for the most threatening bacteria and 143 Motif Bio plc fungi? 145 Mylan NV 29 Portfolios: Which companies produce the most anti- 148 Nabriva Therapeutics plc bacterial and antifungal products? 151 Novartis AG 155 Otsuka Pharmaceutical Co, Ltd 31 RESEARCH AREAS 159 Pfizer Inc 163 Polyphor Ltd 33 RESEARCH & DEVELOPMENT 166 Sanofi 34 How the companies compare in Research & 170 Scynexis Development 172 Shionogi & Co, Ltd 35 In Summary 176 Summit Therapeutics 36 Small & medium-sized enterprises lead in 178 Sun Pharmaceutical Industries Ltd priority research 181 Tetraphase Pharmaceuticals Inc 184 Teva Pharmaceutical Industries Ltd 51 RESPONSIBLE MANUFACTURING 187 Wockhardt Ltd 52 How the companies compare in Responsible Manufacturing 191 APPENDICES 53 In Summary 192 Appendix I: Analysis, scoring and review 54 More companies set antibacterial limits for process wastewaters to minimise AMR risk 195 Appendix II: Limitations 197 Appendix III: Scoring guidelines 65 APPROPRIATE ACCESS & STEWARDSHIP 203 Appendix IV: Identifying best practices 66 How the companies compare in Appropriate Access & 203 Appendix V: Priority pathogens included Stewardship for analysis in R&D 67 In Summary 204 Appendix VI: Access countries 68 Progress in safeguarding use of products, 205 Appendix VII: Guide to Report Cards yet access is still lacking in LMICs 209 Appendix VIII: Figures 210 Appendix IX: Definitions 4 Access to Medicine Foundation About this report The second Antimicrobial Resistance Benchmark com- WHAT WE MEASURE pares how a cross-section of the pharmaceutical industry is The 2020 AMR Benchmark uses a framework of 19 indi- responding to the threat from drug-resistant infections. It cators organised into three Research Areas: Research & evaluates 30 companies with a major stake in the anti-infec- Development; Responsible Manufacturing; and Appropriate tives space, including those with the largest R&D divisions, Access and Stewardship. These correspond to pharmaceuti- the largest market presence, and leading expertise in devel- cal companies’ core responsibilities for limiting AMR: develop- oping critically needed antibiotics and antifungals. These are ing new medicines to replace ones that no longer work, make among the last companies that remain invested in keeping them accessible to those who need them, and find new ways such medicines and vaccines available and developing new to ensure antibiotics are produced and promoted responsibly. ones. The Benchmark assesses company behaviour regarding dis- The 30 companies include eight large R&D-based pharma- eases and product types and in a specific geographic scope, ceutical companies, nine generic medicine manufacturers and depending on the Research Area in question. Its metrics cor- 13 small and medium-sized enterprises. The Benchmark eval- respond to areas where experts and stakeholders agree that uates these companies in areas where they have the biggest pharmaceutical companies can and should be taking action to potential and responsibility to limit AMR, such as R&D, man- limit AMR. aging manufacturing waste and ensuring appropriate access and stewardship. HOW WE MEASURE The Antimicrobial Resistance Benchmark is used as a tool The Benchmark evaluated data gathered via a detailed sur- to guide and stimulate pharmaceutical companies to imple- vey of company behaviour regarding AMR and from pub- ment effective actions for limiting AMR and remain commit- lic sources. It reports company activities taking place during ted to developing new and existing