As part of its ongoing engagement with the life sciences and pharmaceutical industry during the COVID-19 pandemic, the UK Government recently led an online webinar highlighting its efforts to push forward its COVID-19 therapeutics research programme within the UK.
With speakers ranging from Professor Jonathan Van-Tam (Deputy Chief Medical Officer) to Professor Sir Mark Walport (Chief Executive, UK Research and Innovation) it is clear that the UK is bringing to the fore its expertise and knowledge across government, public health and the industry.
Three key themes emerged in the webinar, namely: strategy; progress; and challenges and next steps, which we delve into in further detail below.
The Government’s strategy in respect of COVID-19 therapeutic research appears to be comprised of three central themes: leveraging existing infrastructure; broad collaboration; and flexibility.
In terms of existing infrastructure, it was emphasised that the Government had no intention of ‘re-inventing the wheel’ in meeting the therapeutic demands of the COVID-19 pandemic. This strategic approach was also extended to the repurposing of existing therapies – which we discuss in more detail below. The UK has a world-leading clinical trial framework that can enable trials to progress more rapidly (yet safely) than in other jurisdictions. This leading position has been attained from having an efficient and ethically responsible regulatory regime, as well as the support of the NHS, which has well-established reach and protocols in terms of patient recruitment and data collection. The effects of such a regime were demonstrated in the recent COVID-related tocilizumab trial sponsored by Roche, in which the pace of recruitment and patient number in the UK exceeded that of any other country where the trial is taking place (36 participants recruited in 12 days). Having said that, the NHS is still under considerable pressure – and we pick up on some of those challenges later on.
Collaboration is also key to the Government’s therapeutic strategy, and it is clear that there is considerable interdepartmental co-operation underway. This is intended to avoid excess duplication of studies and efforts. Various formal partnerships exist between the NHS (England and Digital); the Department of Health and Social Care; the Medicines and Healthcare products Regulatory Agency (MHRA); and others. An example of this collaboration is the Government’s central point of contact for new prospective COVID-19 trials, the DHSC Therapeutics Taskforce (the Taskforce). Contacting the Taskforce initiates a triage process which includes participants such as the DHSC, the Government research bodies and the MHRA. At the same time, the Taskforce is ‘horizon scanning’ to identify potential blockages in this complicated landscape, which may develop as the various trials move forward. Industry is also being actively encouraged to collaborate by contacting the Taskforce with new COVID-19 trials.
Finally, in terms of flexibility, it is evident that the Government is focussing on reducing timeframes for therapeutics to move through the trial and approval processes. The triage process is intended to cover a two week process only – which is certainly ambitious. The MHRA has received praise for introducing various regulatory relaxations regarding trials, to ensure there are no unnecessary regulatory roadblocks. It was clear that lessons can be learned from the flexibility being demonstrated during the COVID-19 pandemic and that these can be transferred into the UK’s clinical trial framework in a post-COVID-19 world.
Against this background, considerable progress has been made despite the lack of licensed products for the treatment of COVID-19 at present. There are, however, substantial numbers of trials underway, at different phases. This includes three major trials at Phase III: the PRINCIPLE, RECOVERY and REMAP-CAP trials.
As above, these trials cover existing therapeutic products, such as hydroxychloroquine (which has been the subject of significant publicity recently) and various marketed immunomodulatory and anti-inflammatory compounds. Convalescent plasma is intended to be added to the RECOVERY trial and has been added to the REMAP-CAP trial. Participant numbers in these trials range from the low hundreds in PRINCIPLE to over 10,000 in RECOVERY. Each trial is intended to cover different stages of the infection, with REMAP-CAP involving patients at the ICU stage and, crucially, the Government has had to be nimble in overseeing and managing these trials, to address issues such as primary care facility closure. Further, an impressive effort has been underway to scale up the various clinical trials throughout the pandemic, particularly for the REMAP-CAP trial, which has been rapidly expanded to over 106 sites.
In addition, there is substantial effort in the Government at the early stage development of new COVID-19 treatments. This includes the ACCORD and CATALYST programmes, which are focussed on existing cancer, immunomodulatory and anti-inflammatory products. These Programmes involve rapidly identifying existing Phase II studies of products with potential to treat COVID-19, or initiating smaller studies, and fast-tracking these to Phase III.
Challenges and next steps
There are a number of the unique challenges in developing treatments for COVID-19. These include the closure of primary care clinics, which typically prove invaluable for patient recruitment, as well as data generation in regards to the already significant numbers of trial participants (currently totalling over 72,000). There is also a personnel challenge, insofar as many of the UK’s key researchers have been moved to the frontline. In addition, the decline in new COVID-19 cases, while undoubtedly positive, has created an increasing challenge in recruiting trial patients who have developed sufficient antibodies to combat the virus. This could provide particularly problematic in trying to develop effective treatments before a potential second wave of infections occurs later this year.
Nonetheless, it was apparent from the webinar the considerable efforts underway to support the development of therapeutics for COVID-19, particularly with regard to contributions that personnel have made at all stages. When asked what challenges will emerge when an effective compound is identified, one of the speakers quipped: “that would be a delightful problem to have”. The MHRA, NICE and other bodies are working together on an expedited process to make products available as soon as possible. At this stage, it will be important to fast-track supply as quickly as possible, and the speakers identified a crucial role for industry in ensuring capacity for manufacture and supply.
Going forward, it appears there are solid processes in place to continue to search for effective treatments, although it was noted that a vaccine will be the essential step for returning to ‘life as normal’.