International Journal of Infectious Diseases 131 (2023) 180–182 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Editorial End of the Bedaquiline patent – a crucial development for moving forward affordable drugs, diagnostics, and vaccines for infectious diseases in low- and middle-income countries a ( d t p a v d t p s m c p fi a g p c P T t t m h K t S p t A ( p t w r t f s a p [ W h “ r t M m m s a v c t p a [ m t T o b l s a o d c c t h w b R T h c i h 1 l When Johnson & Johnson (J&J) developed the new tuberculosis TB) drug bedaquiline (Sirturo) [1] , it was one the few new drugs o have been conditionally approved by the United States Food nd Drug Administration (FDA) in 2012 for treatment of multi- rug resistant tuberculosis (MDR-TB). It offered renewed hope to atients providing a unique opportunity to radically transform anagement of MDR-TB to shorter, easier-to-administer, and more atient-tolerable treatment regimens [2] . Evaluation in clinical tri- ls over the ensuing seven years showed that bedaquiline was a ame-changer, demonstrating substantial improved treatment out- omes among people with MDR-TB and extensively drug-resistant B (XDR-TB) [3] . J&J, like all pharmaceutical companies who hold he patent rights on drugs, had the sole authority over setting the igh price of bedaquiline. In October 2019 Médecins Sans Fron- ières (MSF), TB activists and civil society launched a global cam- aign protesting outside J&J offices in the United States, South frica, Brazil, Belgium, Ukraine and Spain calling on lowering the rice of bedaquiline to no more than US$ 1 per day for patients ith MDR-TB, so as to allow rapid scale-up and the ability to reat patients, rendering them non-infectious and reducing further pread within the community [3] . Bedaquiline is now considered n essential drug in an all-oral treatment regimen for MDR-TB 2,4,5] . The rates of MDR-TB have, however, remained extremely igh in Asia, Africa and Eastern Europe and deaths due to drug- esistance remain high [5] . Most of the estimated annual 50 0,0 0 0 DR-TB cases do not have access to oral MDR-TB treatment regi- ens due to their high cost, lack of affordability, and limited avail- bility. The recent rejection by India’s patent office of J&J’s applica- ion to extend their patent on bedaquiline beyond July 2023 for n additional 4 years effectively ends the company’s eight-year onopoly on a crucial drug for oral treatment of MDR/XDR-TB. (5). he challenge to the patent was originally filed in February 2019 y a Mumbai journalist [6] who contracted TB twice and wanted afer oral options tan injectables to be made available for millions f people who could not afford the drug. The decision by the In- ian patent office opens the door for other companies to produce heaper and more accessible versions of bedaquiline, with some ealth experts estimating that the costs of treatment could be cut y 80%, from US$46 ( €42.6) to US$8 ( €7.4) a month per patient [7] . his historic decision by the India patent office clears the way for heaper versions of bedaquiline to be manufactured and be made ttps://doi.org/10.1016/j.ijid.2023.04.386 201-9712/© 2023 The Authors. Published by Elsevier Ltd on behalf of International Socie icense ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) vailable more widely, especially in poor resource high MDR-TB en- emic countries. It is also a critical decision that sets an important recedent for increasing access to affordable drugs, diagnostics and accines for other epidemic diseases affecting resource-poor coun- ries. In April, 2021, a Brazil judge suspended drug patent exten- ions, a preliminary decision that could lower costs for drugs criti- al to treating COVID-19 patients at the expense of pharmaceutical rms [8] . During the COVID-19 pandemic, South Africa and India pro- osed a broad waiver of the Trade-Related aspects of Intellectual roperty (TRIPS) agreement covering COVID-19 vaccines, tests, and reatments to allow enhanced affordable supplies for low- and iddle-income countries (LMICs) [9] . The European Union, United ingdom and Switzerland blocked that proposal, whilst the United tates supported an IP waiver for only vaccines [10] , although his did not happen. In May 2021 the World Trade Organization WTO), published a joint declaration on the importance of Intellec- ual Property Rights (IPRs) to COVID-19 vaccines, stating that “the espect for intellectual property rights is key and will ensure the astest possible production of urgently needed vaccines” [11] . GAVI, the Vaccines Alliance, as well as its other three core artners, the Coalition for Epidemic Preparedness Innovations, the orld Health Organization and UNICEF stated in August 2021 that seventeen COVID-19 vaccines are already in use, 105 in clinical rials and further 184 vaccine candidates in pre-clinical develop- ent. However, given that global demand for these vaccines is everal times larger than the total annual global supply for all accines, we clearly need to do everything in our power to in- rease manufacturing capacity and intellectual property is an im- ortant part of vaccine development and critical for innovation” 12] . COVAX has been a strong supporter of encouraging manufac- urers to share intellectual property and technical know-how with ther manufacturers. COVAX has delivered approximately 1.5 bil- ion doses to LMICs far short of demand and this model TB drug ccess is required. Infectious diseases which are threats to global public health se- urity cannot be controlled by actions of individual pharmaceu- icals or governments, but they need transnational organizations ith adequate funding to ensure unified actions across countries. ecently the Global Fund to Fight AIDS, Tuberculosis and Malaria as been successful in providing low-cost treatment for HIV/AIDS, mpregnated bed nets for malaria and tuberculosis treatment. The ty for Infectious Diseases. This is an open access article under the CC BY-NC-ND E. Petersen, D.S. Hui, J.B. Nachega et al. International Journal of Infectious Diseases 131 (2023) 180–182 d u M i g [ d U d p q a ( t d e t f L i r n c p a c m c m i t t s t f D F A E b P f M L ecision by the Indian patent office is important and local man- facturing in LMICs will ensure more drugs for the treatment of DR/XDR-TB at an affordable budget. A previous program ensur- ng access to drugs and vaccines for LMICs is the World Health Or- anization (WHO)’s Expanded Programme on Immunizations (EPI) 13] , providing cheap vaccines to children in LMICs supported by onors and succeeding in negotiating lower prices through coor- inated bulk purchase. This is a model for exploring differential ricing between LMICs and industrialized countries to ensure ade- uate vaccine supplies to LMICs. This also applies to development nd rollout of affordable diagnostics. The outbreak of monkeypox mpox) and the emergence of other pathogens with epidemic po- ential [14,15] underline the fact that the lack of reliable and cheap iagnostics in many LMICs impaired proper assessment of dis- ase epidemiology, detection and response capacities [16] . Access o rapid diagnostics, treatments and vaccines is critical in all in- ectious disease outbreaks with pandemic potential. To accelerate mpact, greater collaboration between public and private sectors is equired so that capabilities and experiences can be jointly har- essed for an enhanced multiplier effect. In conclusion, while patent rights should be preserved to en- ourage development of new drugs, vaccines and diagnostics, im- lementing mechanisms to ensure adequate supplies worldwide re urgently needed. This includes expansion of manufacturing fa- ilities to LMICs providing employment and professional develop- ent opportunities, donation programs funded by industrialized ountries, and price reductions through bulk purchase arrange- ent. The buzz phrase “no one is safe unless everyone is safe” s very true and the COVID-19 pandemic once again underlined hat. When new products that could save lives or prevent infec- ions are developed by pharmaceutical companies, it becomes es- ential that in resource-limited settings they are made affordable hrough equity-based tiered pricing or having shorter patents for acilitating widespread manufacturing. eclaration of competing interest All authors declare no conflicts of interest. unding None. cknowledgements AZ, DYM, FN are members of The Pan-African Network on merging and Re-Emerging Infections (PANDORA-ID-NET) funded y the EU European and Developing Countries Clinical Trials artnership (EDCTP). AZ is in receipt of a UK-National Institute or Health and Care Research Senior Investigator award and, is a ahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize aureate. Eskild Petersen∗ Institute for Clinical Medicine, Faculty of Health Sciences, University of Aarhus, Denmark European Society for Clinical Microbiology and Infectious Diseases Task Force for Emerging Infections, Basel, Switzerland International Society for Infectious Diseases David S. Hui Department of Medicine & Therapeutics and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China 181 Jean B. Nachega Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Division of Infectious Diseases, Department of Medicine, Stellenbosch niversity, Faculty of Medicine and Health Sciences Cape Town, South Africa Francine Ntoumi Fondation Congolaise pour la Recherche Médicale, Brazzaville, Republic of Congo Institute of Tropical Medicine, University of Tübingen, Germany Delia Goletti International Society for Infectious Diseases Translational Research Unit, National Institute for Infectious Diseases azzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy Eleni Aklillu Division of Clinical Pharmacology, Department of Global Public Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Avinash Sharma Department of Biotechnology National Centre for Cell Science, Pune, India Thomas Nyirenda European Developing Countries Clinical rials partnership (EDCTP) Africa Office, Cape Town, South Africa Dorothy Yeboah-Manu Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana Giovanni Satta Department of Microbiology, UCL Hospitals NHS Foundation Trust, London, United Kingdom Christopher da Costa Coalition for Epidemic Preparedness Innovations, Washington, DC, USA Esam I. Azhar Special Infectious Agents Unit BSL-3, King Fahd Medical Research Center, and Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia Moses Bockarie International Society for Infectious Diseases European Developing Countries Clinical rials partnership (EDCTP) Africa Office, Cape Town, South Africa School of Community Health Sciences, Njala University, Bo, Sierra Leone Seif Al-Abri Directorate General for Disease Surveillance and Control, Ministry of Health, Muscat, Oman Timothy D. McHugh Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, London, UK Alfonso J. Rodriguez-Morales Master’s Program of Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru Gilbert and Rose- Marie Chagoury School of Medicine, Lebanese American University, Beirut 1102, Lebanon E. Petersen, D.S. Hui, J.B. Nachega et al. International Journal of Infectious Diseases 131 (2023) 180–182 B [ [ [ [ R [ [ [ George M Varghese Department of Medicine and Infectious Diseases, Christian Medical College, Vellore, India Alimuddin Zumla Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London and NIHR iomedical Research, Centre, University College London Hospitals NHS Foundation Trust, London NW1 OPE, UK ∗Correspondence author. E-mail addresses: eskild.petersen@gmail.com (E. Petersen), dschui@cuhk.edu.hk (D.S. Hui), jbn16@pitt.edu (J.B. Nachega), fntoumi@fcrm-congo.com (F. Ntoumi), delia.goletti@inmi.it (D. Goletti), Eleni.Aklillu@ki.se (E. Aklillu), avinash.nccs@gmail.com (A. Sharma), nyirenda@edctp.org (T. Nyirenda), DYeboah-Manu@noguchi.ug.edu.gh (D. Yeboah-Manu), giovanni.satta@nhs.net (G. Satta), chrisdacosta26@gmail.com (C. da Costa), eazhar@kau.edu.sa (E.I. Azhar), bockarie@edctp.org (M. Bockarie), salabri@gmail.com (S. Al-Abri), t.mchugh@ucl.ac.uk (T.D. McHugh), arodriguezmo@cientifica.edu.pe (A.J. Rodriguez-Morales), georgemvarghese@hotmail.com (G.M. Varghese), a.zumla@ucl.ac.uk (A. Zumla) eferences [1] TB Alliance-our pipeline. Bedaquiline. https://www.tballiance.org/portfolio/ compound/bedaquiline - accessed 3 April, 2023 [2] WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. https://www.who.int/ publications/i/item/9789240063129 - accessed 3 April, 2023 [3] MSF demands Johnson & Johnson reduce price of lifesaving TB drug. https://www.msf.org/johnson- johnson- must- halve- price- lifesaving- tb- drug- bedaquiline - accessed 3 April, 2023 [4] Nyang’wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Field- ing K. TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med 2022 Dec 22; 387 (25):2331–43. doi: 10.1056/NEJMoa2117166 . 182 [5] WHO Global Tuberculosis Report 2022. https://www.who.int/teams/ global- tuberculosis- programme/tb- reports/global- tuberculosis- report- 2022 - accessed 3 April 2023. [6] Patent opposition database: Bedaquiline Decision, (1220/Mumnp/2009). https: //www.patentoppositions.org/en/drugs/bedaquiline/patent _ office _d ecisions/ 641c1136d2708f0 0 050ab275 - accessed 3 April, 2023 [7] Amrit Dhillon. Victory over big pharma opens door to cheaper tuberculo- sis drugs. https://www.theguardian.com/global-development/2023/mar/29/ victory-over-big-pharma-opens-door-to-cheaper-tuberculosis-drugs-india - accessed 2 April 2023. [8] Reuters. Brazil judge suspends drug patent extensions, move may lower COVID-19 treatment costs. https://www.reuters.com/business/healthcare- pharmaceuticals/brazils- top- court- rule- patent- case- may- lower- covid- 19- drug- costs- 2021- 04- 07/ (Accessed 5 April 2023). [9] Kohler J, Wong A, Tailor L. Improving Access to COVID-19 Vaccines: An Anal- ysis of TRIPS Waiver Discourse among WTO Members, Civil Society Orga- nizations, and Pharmaceutical Industry Stakeholders. Health Hum Rights Dec 2022; 24 (2):159–75 PMID: 36579316PMCID: PMC9790937 . 10] Oxfam International. WTO agrees a deal on patents for COVID vaccines - but campaigners say this is absolutely not the broad intellectual property waiver the world desperately needs. https://www.oxfam.org/en/press-releases/ wto-agrees-deal-patents-covid-vaccines-campaigners-say-absolutely-not- broad - accessed 3 April, 2023 11] World Trade Organization, WTO. A joint declaration on the importance of IPRs to Covid vaccine manufacturing scale-up and future pandemic preparedness. May 2021. https://www.wto.org/english/tratop _ e/covid19 _ e/iprs _ declaration _ e. pdf - accessed 3 April 2023 12] GAVI. Intellectual Property and COVID-19 vaccines. 3 August 2021. https:// www.gavi.org/vaccineswork/intellectual-property-and-covid-19-vaccines - ac- cessed 3 April 2023 13] WHO. Essential Programme on Immunization. https://www.who.int/ teams/immunization- vaccines- and- biologicals/essential- programme- on- immunization - accessed 3 April, 2023 14] ECDC. Epidemiological data on the 2022 mpox (monkeypox) outbreak. 14 Sept 2022. https://www.ecdc.europa.eu/en/infectious- disease- topics/z- disease- list/ mpox-monkeypox/epidemiological-data-2022-mpox-monkeypox - accessed 3 April 2023 15] Petersen E, Abubakar I, Ihekweazu C, Heymann D, Ntoumi F, Blumberg L, et al. Monkeypox - Enhancing public health preparedness for an emerging lethal hu- man zoonotic epidemic threat in the wake of the smallpox post-eradication era. Int J Infect Dis Jan 2019; 78 :78–84. doi: 10.1016/j.ijid.2018.11.008 . 16] Nachega JB, Nsanzimana S, Rawat A, Wilson LA, Rosenthal PJ, Siedner MJ, et al. Advancing detection and response capacities for emerging and re-emerging pathogens in Africa. Lancet Infect Dis 2022 S1473-3099(22)00723-X. doi: 10. 1016/S1473- 3099(22)00723- X .