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.

When Johnson & Johnson (J&J) developed the new tuberculosis (TB) drug bedaquiline (Sirturo) [[1]TB Alliance-our pipeline. Bedaquiline. https://www.tballiance.org/portfolio/compound/bedaquiline - accessed 3 April, 2023Google Scholar], it was one the few new drugs to have been conditionally approved by the United States Food and Drug Administration (FDA) in 2012 for treatment of multi-drug resistant tuberculosis (MDR-TB). It offered renewed hope to patients providing a unique opportunity to radically transform management of MDR-TB to shorter, easier-to-administer, and more patient-tolerable treatment regimens [[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, 2023Google Scholar]. Evaluation in clinical trials over the ensuing seven years showed that bedaquiline was a game-changer, demonstrating substantial improved treatment outcomes among people with MDR-TB and extensively drug-resistant TB (XDR-TB) [[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, 2023Google Scholar]. J&J, like all pharmaceutical companies who hold the patent rights on drugs, had the sole authority over setting the high price of bedaquiline. In October 2019 Médecins Sans Frontières (MSF), TB activists and civil society launched a global campaign protesting outside J&J offices in the United States, South Africa, Brazil, Belgium, Ukraine and Spain calling on lowering the price of bedaquiline to no more than US$ 1 per day for patients with MDR-TB, so as to allow rapid scale-up and the ability to treat patients, rendering them non-infectious and reducing further spread within the community [[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, 2023Google Scholar]. Bedaquiline is now considered an essential drug in an all-oral treatment regimen for MDR-TB [2WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. https://www.who.int/publications/i/item/9789240063129 - accessed 3 April, 2023Google Scholar, 4Nyang'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 Fielding K TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis.N Engl J Med. 2022 Dec 22; 387: 2331-2343https://doi.org/10.1056/NEJMoa2117166Crossref PubMed Scopus (27) Google Scholar, 5WHO Global Tuberculosis Report 2022. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022 - accessed 3 April 2023.Google Scholar]. The rates of MDR-TB have, however, remained extremely high in Asia, Africa and Eastern Europe and deaths due to drug-resistance remain high [[5]WHO Global Tuberculosis Report 2022. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022 - accessed 3 April 2023.Google Scholar]. Most of the estimated annual 500,000 MDR-TB cases do not have access to oral MDR-TB treatment regimens due to their high cost, lack of affordability, and limited availability. The recent rejection by India's patent office of J&J's application to extend their patent on bedaquiline beyond July 2023 for an additional 4 years effectively ends the company's eight-year monopoly on a crucial drug for oral treatment of MDR/XDR-TB. (5). The challenge to the patent was originally filed in February 2019 by a Mumbai journalist [[6]Patent opposition database: Bedaquiline Decision, (1220/Mumnp/2009). https://www.patentoppositions.org/en/drugs/bedaquiline/patent_office_decisions/641c1136d2708f00050ab275 - accessed 3 April, 2023Google Scholar] who contracted TB twice and wanted safer oral options tan injectables to be made available for millions of people who could not afford the drug. The decision by the Indian patent office opens the door for other companies to produce cheaper and more accessible versions of bedaquiline, with some health experts estimating that the costs of treatment could be cut by 80%, from US$46 (€42.6) to US$8 (€7.4) a month per patient [[7]Amrit Dhillon. Victory over big pharma opens door to cheaper tuberculosis 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.Google Scholar]. This historic decision by the India patent office clears the way for cheaper versions of bedaquiline to be manufactured and be made available more widely, especially in poor resource high MDR-TB endemic countries. It is also a critical decision that sets an important precedent for increasing access to affordable drugs, diagnostics and vaccines for other epidemic diseases affecting resource-poor countries. In April, 2021, a Brazil judge suspended drug patent extensions, a preliminary decision that could lower costs for drugs critical to treating COVID-19 patients at the expense of pharmaceutical firms [[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).Google Scholar]. During the COVID-19 pandemic, South Africa and India proposed a broad waiver of the Trade-Related aspects of Intellectual Property (TRIPS) agreement covering COVID-19 vaccines, tests, and treatments to allow enhanced affordable supplies for low- and middle-income countries (LMICs) [[9]Kohler J Wong A Tailor L Improving Access to COVID-19 Vaccines: An Analysis of TRIPS Waiver Discourse among WTO Members, Civil Society Organizations, and Pharmaceutical Industry Stakeholders.Health Hum Rights. Dec 2022; 24 (PMID: 36579316PMCID: PMC9790937): 159-175PubMed Google Scholar]. The European Union, United Kingdom and Switzerland blocked that proposal, whilst the United States supported an IP waiver for only vaccines [[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, 2023Google Scholar], although this did not happen. In May 2021 the World Trade Organization (WTO), published a joint declaration on the importance of Intellectual Property Rights (IPRs) to COVID-19 vaccines, stating that “the respect for intellectual property rights is key and will ensure the fastest possible production of urgently needed vaccines” [[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 2023Google Scholar]. GAVI, the Vaccines Alliance, as well as its other three core partners, the Coalition for Epidemic Preparedness Innovations, the World Health Organization and UNICEF stated in August 2021 that “seventeen COVID-19 vaccines are already in use, 105 in clinical trials and further 184 vaccine candidates in pre-clinical development. However, given that global demand for these vaccines is several times larger than the total annual global supply for all vaccines, we clearly need to do everything in our power to increase manufacturing capacity and intellectual property is an important part of vaccine development and critical for innovation” [[12]GAVI. Intellectual Property and COVID-19 vaccines. 3 August 2021. https://www.gavi.org/vaccineswork/intellectual-property-and-covid-19-vaccines - accessed 3 April 2023Google Scholar]. COVAX has been a strong supporter of encouraging manufacturers to share intellectual property and technical know-how with other manufacturers. COVAX has delivered approximately 1.5 billion doses to LMICs far short of demand and this model TB drug access is required. Infectious diseases which are threats to global public health security cannot be controlled by actions of individual pharmaceuticals or governments, but they need transnational organizations with adequate funding to ensure unified actions across countries. Recently the Global Fund to Fight AIDS, Tuberculosis and Malaria has been successful in providing low-cost treatment for HIV/AIDS, impregnated bed nets for malaria and tuberculosis treatment. The decision by the Indian patent office is important and local manufacturing in LMICs will ensure more drugs for the treatment of MDR/XDR-TB at an affordable budget. A previous program ensuring access to drugs and vaccines for LMICs is the World Health Organization (WHO)’s Expanded Programme on Immunizations (EPI) [[13]WHO. Essential Programme on Immunization. https://www.who.int/teams/immunization-vaccines-and-biologicals/essential-programme-on-immunization - accessed 3 April, 2023Google Scholar], providing cheap vaccines to children in LMICs supported by donors and succeeding in negotiating lower prices through coordinated bulk purchase. This is a model for exploring differential pricing between LMICs and industrialized countries to ensure adequate vaccine supplies to LMICs. This also applies to development and rollout of affordable diagnostics. The outbreak of monkeypox (mpox) and the emergence of other pathogens with epidemic potential [14ECDC. 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 2023Google Scholar, 15Petersen E Abubakar I Ihekweazu C Heymann D Ntoumi F Blumberg L et al.Monkeypox - Enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era.Int J Infect Dis. Jan 2019; 78: 78-84https://doi.org/10.1016/j.ijid.2018.11.008Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar] underline the fact that the lack of reliable and cheap diagnostics in many LMICs impaired proper assessment of disease epidemiology, detection and response capacities [[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)https://doi.org/10.1016/S1473-3099(22)00723-XAbstract Full Text Full Text PDF Scopus (2) Google Scholar]. Access to rapid diagnostics, treatments and vaccines is critical in all infectious disease outbreaks with pandemic potential. To accelerate impact, greater collaboration between public and private sectors is required so that capabilities and experiences can be jointly harnessed for an enhanced multiplier effect. In conclusion, while patent rights should be preserved to encourage development of new drugs, vaccines and diagnostics, implementing mechanisms to ensure adequate supplies worldwide are urgently needed. This includes expansion of manufacturing facilities to LMICs providing employment and professional development opportunities, donation programs funded by industrialized countries, and price reductions through bulk purchase arrangement. The buzz phrase “no one is safe unless everyone is safe” is very true and the COVID-19 pandemic once again underlined that. When new products that could save lives or prevent infections are developed by pharmaceutical companies, it becomes essential that in resource-limited settings they are made affordable through equity-based tiered pricing or having shorter patents for facilitating widespread manufacturing. All authors declare no conflicts of interest. None.