Rising to the challenge: the response of UK biopharmaceuticals to the COVID-19 pandemic

Hindsight is a gift that every politician desires and with it, perhaps we would have been better prepared for the COVID-19 pandemic, acted more quickly, with greater certainty and ultimately more effectively.

Given that this is a new disease, which was first characterised at the end of 2019, the UK biopharma industry (and the global biopharma industry for that matter) has responded quickly and positively and the resulting understanding and treatment globally has been impressive. That said, in the middle of 2020, the pandemic is still advancing strongly around the world. The ability of the UK biopharma industry to respond and innovate is being tested in this crisis and to date it has shown great flexibility and ingenuity across epidemiology, vaccines, therapeutics and diagnostics.

Epidemiology

Understanding COVID-19 epidemiology[1] was and continues to be central to government decision making. The evolution of the understanding of how this disease is transmitted and its impact on different sectors of the general population was important in informing those government decisions which led to lock-down in the UK. Early on, the academic epidemiologists [2] with their modelling of the disease were at the forefront in interpreting the imperfect data derived from hospitals and general society. They were key in recognising how infectious this virus is and providing the grave predictions as to the potential mortality associated with anything less than a full lock-down response. Epidemiologists have also been advising on how to safely return from lock-down to normality.

Vaccines

There are currently more than 165 vaccine candidates in development, with eight in phase III clinical trials and two approved for use[3]. The Jenner Institute, University of Oxford are currently conducting extensive phase III studies with a chimpanzee adenovirus-vector based vaccine in Africa and Brazil with the expectation that, subject to positive clinical results, the Oxford vaccine can be approved before the end of 2020 (“the Oxford vaccine”). Getting to this stage required input from an experienced vaccine discovery and development team[4], of paramount importance was the early publication of the genetic sequence of the SARS-CoV-2 virus by Chinese scientists which allowed the early development of a wide range of vaccine candidates. For a vaccine to be effective, it needs to not only prove to be safe and effective through clinical trials, but it also needs to be manufactured at a scale which requires enormous financial support (both the UK and US Governments have contributed significant funds for the Oxford vaccine project) as well as accessing the necessary manufacturing capacity to ensure supply of product in a timely manner. This has been assisted by AstraZeneca who supported both the clinical trials and manufacturing as their first venture into vaccine products. It was a bold decision by AstraZeneca, to step up to this challenge in such a profound and impactful way, particularly for a company with no experience in vaccine therapeutics.

Imperial College London is also developing a vaccine (VacEquity Global Health) based on a self-replicating RNA, a new technology which if successful offers the promise of rapid, low cost vaccines. This is among the higher risk vaccine lottery ticket bets. However, following in the development pipeline are vaccines from Pfizer, Merck, Sanofi+GSK and Johnson & Johnson; companies with long track records in both developing and commercialising vaccines at scale, using a variety of technologies, so the omens are good for an effective treatment.

Clinical trials, regulatory and ethics approval committees have reacted with flexibility, innovation and energy to the constantly changing demands of researchers and their trials, allowing the rapid evaluation of new vaccines. Again, these innovations in study design and approval processes will support broader, better, clinical trial protocols and trials beyond this pandemic.

Therapeutics

In June 2020, the UK NHS (The RECOVERY Collaborative Group, a research alliance of NHS hospitals and clinicians) published the results of clinical studies[5] showing a significant clinical benefit from the administration of dexamethasone to hospitalised COVID-19 patients requiring supplemental oxygen or mechanical ventilation. Dexamethasone is a well- known generic glucocorticoid which can modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. It was used in this robust clinical trial conducted in the setting of a rapidly evolving global pandemic across many NHS hospitals. In addition to this, several UK biotechs (including Benevolent AI[6], Exscientia[7] and Healx[8] applied their AI and machine learning platforms to identify therapeutics for the treatment of this disease. The work of Benevolent AI resulted in Baricitinib (an already approved drug developed by Eli Lilly and Incyte for the treatment of rheumatoid arthritis) entering clinical trials for the treatment of complications arising from SARS-CoV-2 virus infections.

Diagnostics

Key to addressing and mitigating this pandemic is the rapid identification, isolation and treatment of those who become infected. Given that asymptotic carriers have been a significant contributor to the spread of this disease, a method for the rapid accurate identification of those infected is needed. In early August 2020, the NHS has adopted two rapid (90 minute) tests[9], developed by Oxford Nanopore and DnaNudge respectively, each using different techniques to identify viral genetic material in saliva and nasal swab samples. The DnaNudge (an Imperial College London spinout) test and analyser was the result of the pivot of a lab in a cartridge technology designed to use consumer genotyping to inform on healthier lifestyle choices. Both illustrated the quality of the proprietary technology and agility of both companies to rapidly adapt and approve both tests.

Where we are now?

Lock-down of the UK happened after the COVID-19 pandemic had become widespread in UK populations. The results of antibody studies[10] suggest that ~6% of the UK population (3.4 million) have been infected with the virus, rising to ~13% of the population of London. This has been translated into approximately 40,000 deaths attributed to this virus. While the UK was clearly late to respond to the serious nature of the pandemic, it is hoped that in the end, the combination of the life science expertise and industry present in the UK will mean that whilst we may have lost some of the early battles relative to other countries, we will all (globally) win the war.

What the future holds

We will be better prepared for the next pandemic. SARS-CoV-2 doesn’t respect national boundaries nor will the next one. What shape this better preparedness will take will have local, national and international elements, all to be determined.

This calamity has shown that healthcare and the life sciences workers are extremely important. The pandemic has also shown us that facts, data, critical analysis and technology are essential for an adequate response whereas lack of data can be fatal. Hopefully it will encourage those choosing careers to consider healthcare and life sciences as sectors where they can make a significant contribution to society and innovation.

The world will be different after this pandemic, it is beholden on all of us to make sure that lessons will be learnt, and we ensure that the world in the next years will be a better and safer place.

Sources:

_{[1]HTTPS://WWW.ECDC.EUROPA.EU/EN/COVID-19/LATEST-EVIDENCE/EPIDEMIOLOGY
[2]HTTPS://WWW.IMPERIAL.AC.UK/MRC-GLOBAL-INFECTIOUS-DISEASE-ANALYSIS/COVID-19/COVID-19-REPORTS/
[3]HTTPS://WWW.NYTIMES.COM/INTERACTIVE/2020/SCIENCE/CORONAVIRUS-VACCINE-TRACKER.HTML
[4]HTTPS://WWW.JENNER.AC.UK/
[5]HTTPS://WWW.NEJM.ORG/DOI/FULL/10.1056/NEJMOA2021436
[6]HTTPS://WWW.BENEVOLENT.COM/NEWS/POTENTIAL-TREATMENT-FOR-COVID-19-IDENTIFIED-BY-BENEVOLENTAI-USING-ARTIFICIAL-INTELLIGENCE-ENTERS-RANDOMISED-CLINICAL-TRIAL
[7]HTTPS://WWW.EXSCIENTIA.AI/NEWS-INSIGHTS/EXSCIENTIA-ANNOUNCES-JOINT-INITIATIVE-TO-IDENTIFY-COVID-19
[8]HTTPS://HEALX.IO/HEALX-USING-AI-TO-FIND-COMBINATION-DRUG-TREATMENTS-FOR-COVID-19/
[9]HTTPS://EDITION.CNN.COM/2020/08/03/HEALTH/90-MINUTE-COVID-19-TESTING-GBR-INTL/INDEX
[10]HTTPS://WWW.IMPERIAL.AC.UK/NEWS/201893/LARGEST-STUDY-HOME-CORONAVIRUS-ANTIBODY-TESTING/}