As we get into late May and various countries are considering lifting lockdown, I’d like to post this weekend a brief overview of three recent developments in COVID-19 treatments and vaccines. First, on 14 May, Cipla (hydroxychloroquine) and Gilead (Remdesivir) signed a licensing agreement wherein Cipla would have the rights to manufacture and distribute Remdesivir without royalties in 127 nations, but excluding developed markets.[1] Practically, as Pharmaceutical Business Review reports, Cipla will receive the manufacturing ‘recipe’ and Active Pharmaceutical Ingredient (API) from Gilead and produce enough product at commercial scales maximising Cipla's landscapes of commercial manufacturing and retail chains in many developing countries.[2] On 30 April 2019 (before the COVID-19 pandemic), Cipla had received FDA approval to manufacture Ambrisentan, a generic form of Gilead’s Letairis which is a medicine for hypertension, though this was after Gilead had already achieved nearly $1 billion in US domestic sales. Possibly other Indian generics, such as Dr Reddy’s Laboratories, may reach an agreement with Gilead.[3] In a future post, I will discuss India’s style of non-aligned and self-reliant foreign diplomacy, because there are some elements reflected in Cipla’s commercial expansion and international engagement.[4]
Second is Japanese vaccine research in Osaka. I’d mentioned in a previous post that due to its planned hosting of EXPO25, Osaka city had asserted its own 'model' towards re-starting economic activity. Whether this is a good idea, the rest of Japan is watching as the emergency is lifted in key areas, but on 17 May no new cases were announced in Osaka’s metropolitan area.[5] It seems the municipality’s intentions to be Japan’s other ‘major city’ also extends to vaccine research. In March, Osaka University announced a local vaccine research collaboration with Osaka University Public Corporation, Osaka City Hospital Organization and the metropolitan area and prefectural government, as well as the University of Tokyo.[6] Osaka Governor Yoshimura Hirofumi has declared this as an ‘All Osaka’ effort 「オール大阪」, though University of Tokyo is a collaborator.
Japanese universities and labs were originally not keen on vaccine research for another influenza-like disease because the previous SARS pandemic had been resolved before major results were produced. However, the difference with Osaka’s approach is that it will work with AnGes MC, Inc. to produce a DNA vaccine[7], which is in theory safer since it tries to trigger an immune response with a synthetic DNA sequence instead of introducing a live infectious agent. It is also easier and faster to develop since it doesn’t require biological cells (less than a month vs. 5-8 months) and will allow prioritisation of speed and safety with accelerated clinical trials.[8] These details were explained by Osaka University Graduate School of Medicine Professor Morishita Ryuichi on 12 May recently as a ‘made in Japan’ vaccine.[9] In a pandemic, vaccine research should logically be progressing in each nation with the primary goal of supplying the domestic population, so speed and safety is of the essence. Japanese people will also feel more comfortable if the product was made in country, since an internationally developed vaccine will take some time to reach geographically distant markets.
The Osaka vaccine research is specifically meant to be safe and quick but also allow people to re-start normal economic activity. Thus, the trade-off is that the DNA vaccine may not have an antibody producing effect on quite a few people, a finding only clinical trials can reveal. To find a ‘perfect’ vaccine with optimised antibody uptake would take at least a year. As for viral strains and mutations, it seems COVID-19 is not mutating enough to warrant completely different approaches to DNA vaccines, a finding the London School of Hygiene and Tropical Medicine is leading with preliminary un-peer reviewed results using genomic analysis technique announced late April.[10] Prime Minister Abe declared on 11 May that if optimistic, trials will begin July 2020.
Third are fund-raising summits for vaccine collaboration, demonstrating several layers of global, regional and historical/geopolitical alignments. On 5 May 2020, countries in the non-aligned movement (NAM) and key officials of UN agencies, including the World Health Organization, held an online summit, chaired by the President of Azerbaijan Ilham Aliyev.[11] A NAM pandemic response was declared, and resulted in a NAM Task Force with a database on humanitarian and medical needs of member states. The European Commission organized a separate summit, but though it was attended by WHO and China, it was not by India, US or Russia.[12] Finally, GAVI’s next donor pledging conference will be hosted by the UK government on 4 June 2020.[13] Indian Prime Minister Narendra Modi has had public conversations with Bill Gates about vaccines and other public health developments that may impact India’s COVID-19 response.[14]
These three developments point to an interesting question about regional and global treatment and vaccine efforts. How does domestic vaccine research sit alongside globally and regionally coordinated vaccine research?
Some other treatment/vaccine developments. On 17 March, Pfizer began working on antivirals, and announced 29 April that it would begin clinical trials in the United States.[15] More vaccine partnerships were announced starting mid-April. GSK with Sanofi on 14 April and Johnson & Johnson with Janssen and Harvard Medical School on 30 March committed 1 billion USD to testing a vaccine candidates in September.[16] There was a small controversy when Sanofi announced its intentions to distribute to the US market first, which the French prime minister protested.[17] India’s vaccine research is also progressing as the Indian Serum Institute and Codagenix announced a partnership.[18] On 1 April, Eli Lilly, Merck and Pfizer announced as American pharmaceuticals the launch of a Global COVID-19 Medical Service Program to ‘empower medical colleagues’.[19] News outlets this week reported Chinese cyber security attacks to gain information on the development of vaccine research.[20] I cannot fully wrap my head around this case because I do not yet see China in HIV treatment negotiations, other than WHO getting reports of Chinese research on alternative traditional medicine for managing HIV symptoms.[21] I will keep this theme in mind, because it is a different mode of external engagement from India. Finally, domestic controversies between US bureaucracies over which treatment is authorised and promoted for what purpose emerged when former BARDA head Rick Bright made a whistleblower complaint, accusing corruption and 'unscientific' retaliatory measures by FDA.[22]
Even more so than with HIV/AIDS, resource allocation has been a key focus of discussions around treatment, since these are for moderate to serious clinical cases. Efforts to resolve the most severe parts of the problem should not overwhelm the scale of the original problem. As my recent post discussed (Germany, Netherlands, USC), more people than originally thought are infected and showing antibodies with no symptoms. This was known very early on by the general public, at least in the UK, as many participated in social distancing (prior to testing being widely available) in case they inadvertently transmitted the virus to those more vulnerable. Thus, most people are aware that the treatment section of the pharmaceutical/research sector should not expand to take up a percentage of resources that ultimately does not solve the overall problem. A similar situation happened with both AIDS development aid and the HIV vaccine research industry, though of course in that case, there were much fewer cases of natural recovery or immunity and treatment fundamentally changed the conversation around public health measures (some would say, too much).
Perhaps Cipla and Gilead saw themselves as friendly competitors against more established patented pharma houses. Or they were trying to find a place for the pharmaceutical sector as a whole in a global pandemic that relies primarily on public health measures, like lockdown and social distancing. If generics and patented pharma are complete ideological antagonists, why would an agreement like this happen? I think the more interesting question is: has the dialogue between generics and patented pharma evolved since HIV/AIDS, to a place where both realize they are solving different areas of the same problem? I also wonder if this agreement (since Cipla is arguably the leader of the generic industry) is an offshoot of the 2010 Medicines Patents Pool.[23]
In sum, the collective national and global goals are and should be a balance between: reduce cases with evidence-based knowledge of transmission, continue exploring why and how many do not progress to serious symptoms, treat and understand specific clinical cases of those who have shown severe symptoms, investigate specific cases of each individual person that succumbed to COVID-19, and work with caution, accounting for the worst case scenario, towards getting back to a normal pace of life. Each sector is playing some role in one or more of these aspects.
[1] Amit Mudgill, ‘Will Gilead’s Covid-19 drug lift sustain for Jubilant Life, Cipla?’, 15 May 2020, Economic Times India. <https://economictimes.indiatimes.com/markets/stocks/news/will-gileads-covid-19-drug-lift-sustain-for-jubilant-life-cipla/articleshow/75751845.cms>. [2] PBR Staff Writer, ‘Cipla enters into a licensing agreement with Gilead to expand access to Covid-19 treatment’, 14 May 2020. <https://www.pharmaceutical-business-review.com/news/cipla-enters-into-a-licensing-agreement-with-gilead-to-expand-access-to-covid-19-treatment/>. [3] Cipla, ‘Press Release: Cipla receives final approval for generic version of Gilead Sciences, Inc’s Letairis® (Ambrisentan Tabs, 5 mg & 10 mg)’, <https://www.cipla.com/sites/default/files/Cipla%20receives%20final%20approval%20for%20generic%20version%20of%20Gilead%20Sciences%2C%20Inc%E2%80%99s%20Letairis%C2%AE%20%28Ambrisentan%20Tabs%2C%205mg%20%26%2010mg%29.pdf>. [4] A recent book on this is David Engerman’s The Price of Aid. The archival data is from United States, Russia and India, and shows the character of India’s non-alignment. [5] FNNプライムオンライン, 「新型コロナ感染者 大阪なし 東京は５人 全国でこれまでに２０人感染」, (17 May 2020). <https://youtu.be/5vy0PaVdT0U>. [6] Osaka University, 「大阪府・大阪市などと、新型コロナウィルス感染症にかかる予防ワクチン・治療薬等の研究開発に係る連携に関する協定を締結しました」15 April 2020. <https://www.osaka-u.ac.jp/ja/news/topics/2020/04/1501>. [7] World Health Organization, ‘DNA vaccines’, <https://www.who.int/biologicals/areas/vaccines/dna/en/>. [8] FNN プライムオンライン,「新型コロナのワクチン開発へ 最短６ヶ月以内に試験」、 5 March 2020. <https://youtu.be/0b2mMyzFvF4>; MBS NEWS, 「大阪大学で新型コロナウィルスの『D N Aワクチン』開発中。。。従来ワクチンとの違いは？」, 24 March 2020. <https://youtu.be/fgILX2FJDY4> . [9] FNNプライムオンライン「解説『DNAワクチン』界初級ピッチ 副作用・製法 従来型との違い」12 May 2020. <https://youtu.be/Z4nSV9S-ygA>. [10] LSHTM, ‘How is the COVID-19 virus evolving?’, 7 May 2020. <https://www.lshtm.ac.uk/newsevents/news/2020/how-covid-19-virus-evolving>. [11] Esmira Jafarova, ‘Non-Aligned Movement is “United Against Covid-19”’, Euractiv (5 May 2020). <https://www.euractiv.com/section/azerbaijan/opinion/non-aligned-movement-is-united-against-covid-19/>; ‘NAM CoB adopted Comunique on the COVID-19 Pandemic’, 6 April 2020, <https://namazerbaijan.org/news/32>. [12] Patrick Wintour, ‘World leaders pledge €7.4bn to research Covid-19 vaccine’, 4 May 2020. <https://www.theguardian.com/world/2020/may/04/world-leaders-pledge-74bn-euros-to-research-covid-19-vaccine>. [13] Jay Greene, ‘The billionaire who cried pandemic’, The Washington Post (2 May 2020) <https://www.washingtonpost.com/technology/2020/05/02/bill-gates-coronavirus-science/>; Gavi, ‘Virtual Conference’, <https://www.gavi.org/investing-gavi/resource-mobilisation-process/gavis-3rd-donor-pledging-conference-june-2020> [14] The Gates Foundation was active in the country, along with DFID and the World Bank, and was particularly known for being a key implementer of Indian government initiatives. India’s death count of 2872 as of 16 May 2020 has received some scrutiny, as testing is still not widely available. I will discuss in future how much India’s surveillance infrastructure was upgraded as a result of the AIDS epidemic and whether it is robust enough to deal with a different type of epidemic. Anup Malani, Arpit Gupta & Reuben Abraham, ‘Why does India have so few Covid-19 cases and deaths?’, Quartz India (16 April 2020) <https://qz.com/india/1839018/why-does-india-have-so-few-coronavirus-covid-19-cases-and-deaths/>; Amy Kazmin, ‘India’s Covid-19 case numbers overtake China’s official tally’, Financial Times, 16 May 2020. <https://www.ft.com/content/0187857a-3d2d-37e1-9749-d9789ac08591>. Indian Express Online, ‘PM Modi and Bill Gates discuss Covid-19 via video conferencing’, <https://www.youtube.com/watch?v=Hkjn0AlDg1s&feature=emb_logo>. Express Web Desk, ‘In meeting with Bill Gates, PM Modi discusses post-Covid world, vaccine to cure pandemic’, Indian Express, 15 May 2020. <https://indianexpress.com/article/india/narendra-modi-pm-bill-gates-coronavirus-covid-19-6411039/>. [15] Phil Taylor, ‘Pfizer will start COVID-19 vaccine trial in US next week’, Pharma Phorum, 29 April 2020. <https://pharmaphorum.com/news/pfizer-will-start-coronavirus-vaccine-trial-in-us-next-week/>. [16] Johnson & Johnson, ‘Johnson & Johnson Announces a Lead Vaccine Candidate for COVID-19’, 30 March 2020. <https://www.jnj.com/johnson-johnson-announces-a-lead-vaccine-candidate-for-covid-19-landmark-new-partnership-with-u-s-department-of-health-human-services-and-commitment-to-supply-one-billion-vaccines-worldwide-for-emergency-pandemic-use>. [17] ‘Coronavirus Sanofi: French drug giant rows back after vaccine storm’, BBC, 14 May 2020. <https://www.bbc.co.uk/news/world-europe-52659510>. [18] Ben Winck, ‘Hedge fund billionaire Jim Simons is betting millions on a small biotech firm and its potential coronavirus vaccine’, Markets Insider, 27 February 2020. https://markets.businessinsider.com/news/stocks/coronavirus-vaccine-development-jim-simons-codagenix-biotech-hedge-fund-billionaire-2020-2-1028946644 [19] Pfizer, ‘Medical professionals across Merck, Pfizer and Eli Lilly activate to support health systems’, 1 April 2020. <https://www.pfizer.com/news/press-release/press-release-detail/medical_professionals_across_merck_co_inc_pfizer_inc_and_eli_lilly_and_company_activate_to_support_health_systems_first_responders_and_patients_amid_covid_19_pandemic>. [20] Gordon Corera, ‘Coronavirus: Cyber-spies seek coronavirus vaccine secrets’, BBC, (1 May 2020). <https://www.bbc.co.uk/news/technology-52490432>. [21] Jon Cohen, ‘COVID-19 vaccine protects monkeys from new coronavirus, Chinese biotech reports’, Science, 23 April 2020. <https://www.sciencemag.org/news/2020/04/covid-19-vaccine-protects-monkeys-new-coronavirus-chinese-biotech-reports>. [22] Jon Cohen and Charles Piller, ‘Emails offer look into whistleblower charges of cronyism behind potential COVID-19 drug’, Science 13 May 2020. <https://www.sciencemag.org/news/2020/05/emails-offer-look-whistleblower-charges-cronyism-behind-potential-covid-19-drug#>; Pharma intelligence, ‘Pink Sheet Podcast: Rick Bright leaves BARDA, COVID-19 drug shortage, Part D Preferred Tier’, 27 April 2020. <https://www.youtube.com/watch?v=WO06KCjCj_E>. [23] I wonder what the negotiations were like. I’d like to do a future project, looking at archives of both (if I can get to Mumbai), and conduct oral history interviews with representatives from both industries: how is the ‘problem’ framed, what was the attitude of the negotiation, did you feel a mutual understanding was reached, what other business industries’ business models (fashion, gaming, etc.) inspired you to collaborate? For an activist perspective on the Medicines Patents Pool, see Jennifer Chan, Politics in the Corridors of Dying (Johns Hopkins University Press).