This is a brief update/summary post to follow up my first post on production capacity and Indian generics. Key to note is that hydroxychloroquine (orally administered tablet) has not yet been approved by the US Food and Drug Administration (FDA). In other treatment news, on 1 May, the US FDA gave emergency authorization for Remdesivir and on 2 May Japan also began the approval process for Remdesivir as a potential COVID-19 treatment, the first in the country.[1] Remdesivir, an antiviral, was originally developed to treat Ebola in a collaborative research venture between the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and California-based Gilead Sciences.[2] Established in 1987, one of the first products of the American biotech company Gilead was antiviral therapies. This work began at the tail end of the Cold War and built upon joint virology research by Erik De Clercq (Belgian virologist at KU Leuven) and AntonÃn Holý (Czech chemist Institute of Organic Chemistry and Biochemistry) and funded by American biotech Gilead.[3]
According to the company’s website, there are three strands to its pandemic response, which include clinical trials, emergency access outside clinical trials, and increasing manufacturing and supply.[4] In order to receive FDA approval as quickly as possible, Gilead itself began clinical trials for safety and efficacy enrolling 1000 patients in the initial phase. Separate trials are being conducted by the China-Japan Friendship Hospital in Hubei, the US National Institute of Allergy and Infectious Diseases (NIAID) and Institut National de la Santé et de la Recherche Médicale (INSERM) in France using WHO protocol. In all these cases, Gilead provided Remdesivir at no cost, what is termed ‘compassionate use’.[5]
On 23 April, a small controversy occurred when the World Health Organization accidentally posted a pre-peer reviewed summary of the China Gilead trials’ early findings, which indicated ‘negative’ findings on the drug’s efficacy.[6] This was screen captured by three reporters (Ed Silverman, Adam Feuerstein and Matthew Herper) for STAT, a medical, health, biotech and life sciences journalism outlet. Gilead responded that the study was not able to recruit enough participants and had to be terminated early and therefore, the results should be viewed across the board along with the results of other larger clinical trials ongoing.
Under individual ‘compassionate use’, Gilead has promised to provide the drug to pregnant women and children under 18 with confirmed cases and severe symptoms. It is also preparing expanded access programs in US, France, UK, Germany, Italy, Spain and Switzerland. The third strand of Gilead’s emergency COVID-19 response is improving manufacturing and production scale. The intravenously delivered drug is a little more cumbersome to administrate. As of January 2020, the company was not actively manufacturing Remdesivir, only having enough finished stock to treat 5,000 patients. The targets set are: to have 140,000 treatment courses by the end of May 2020; 500,000 by October 2020; 1,000,000 by December 2020, and several million next year. According to the company website:
‘Since [January], we have proactively and rapidly scaled our supply chain. As of late March, using the active ingredient we already had in our inventory, we have increased our supply to more than 30,000 patient courses of remdesivir on hand, assuming a 10-day course of treatment for patients. As new raw materials arrive over the next few weeks from manufacturing partners around the world, our available supply will begin to rapidly increase.’
Gilead's response will be interesting from the framework of global health and access to medicines. Major business news outlets such as Bloomberg have framed Gilead’s response as a conflict between emergency/humanitarian response versus returns on investment.[7] According to Geoff Porges, an analyst at SVB Leerink LLC (as quoted in the Bloomberg article):
‘What’s special about Covid? Should we assume the capital returns and the profitability for providing a global treatment for Covid long-term, after the first 200,000 or 300,000 courses are provided on a donation basis? Should we assume the returns are going to be similar to the returns you have generated in other parts of the business?’
Upcoming posts plan to focus on plasma therapy, another potential COVID-19 treatment, and how biotech research is contracted between universities and researchers. What exactly is the division of labor between established pharmaceutical houses, emerging small biotech enterprises, chemical raw material suppliers, university research centres and generic pharmaceuticals; and how territorial and competitive are such dialogues? For instance, the Korean chemical company that contacted WHO in 1988 with the offer to produce azidothymidine at a third of the price was also in the process of negotiating a joint-venture with Burroughs-Wellcome. Why did the chemical company extend the offer to both WHO and Burroughs-Wellcome?
If I have enough data, I would like to unpack the financing of these biotech companies, as business and investment news sources are a potentially very interesting primary source base to unravel the evolution of the biotech industry. SVB Leerink LLC is a Boston-based ‘specialist investment bank focusing on the healthcare sector’, founded in 1995. Its parent company is Silicon Valley Bank, founded 1983 in California as a high-tech start-up funder. For my own research, I wonder how investors remember Wellcome Burrough’s Retrovir: a success or failure?
[1] <https://www3.nhk.or.jp/news/html/20200502/k10012415781000.html> <https://www.bloomberg.com/news/articles/2020-05-02/japan-starts-special-approval-process-for-remdesivir-nhk-says>. [2] USAMRIID, ‘Antiviral Compound Provides Full Protection from Ebola Virus in Nonhuman Primates’, 9 October 2015. <https://www.usamriid.army.mil/press_releases/Travis%20ID%20Week%20FINAL.pdf> [3] Erik De Clercq is a pioneering researcher in nucleotide analogs, which revolutionised antiviral treatment research. Oral history interview with De Clercq, recalling the state of the field of virology at the time HIV/AIDS became a crisis during the late 1980s and the waning of the Cold War, accessible here: https://www.avcr.cz/en/news-archive/The-Fascinating-Story-about-Suppressing-HIV/. See also: Renilde Loeckx, Cold War Triangle: How Scientists in East and West Tamed HIV (Leuven University Press, 2017). [4] https://www.gilead.com/purpose/advancing-global-health/covid-19/about-remdesivir [5] ‘Compassionate Use of Remdesivir for Patients with Severe Covid-19’, The New England Journal of Medicine (10 April 2020). [6] https://time.com/5826618/remdesivir-leaked-data-who-website/ https://www.statnews.com/2020/04/23/data-on-gileads-remdesivir-released-by-accident-show-no-benefit-for-coronavirus-patients/ [7] https://www.bloomberg.com/news/articles/2020-04-30/gilead-beats-estimates-but-cautions-that-covid-19-clouds-outlook