The government-sponsored ACCORD (Accelerating COVID-19 Research & Development) platform is a new, single Phase II clinical trial platform launched in the UK to fast-track research into potential treatments and is part of a co-ordinated therapeutic development pathway that the UK Government has put in place as part of the overall Therapeutics Taskforce.
Funded by the Department of Health and Social Care and UK Research and Innovation, ACCORD has been made possible by partnership working between the Government Scientific Office, the National Institute for Health Research’s Biomedical Research Centres and Clinical Research Facilities, and expert centres in Northern Ireland, Scotland and Wales, clinical research company IQVIA, and AstraZeneca. The ACCORD platform has received rapid regulatory approval and will immediately begin enrolment of COVID-19 patients.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said:"AstraZeneca is committed to the challenge of finding new solutions to fight COVID-19 by investigating the novel application of new and existing medicines. As part of ACCORD, we will harness our scientific expertise and experience of developing respiratory medicines to support the rapid upscaling of development and clinical trials."
The ACCORD scientific review panel has prioritised the first six molecules for entry into the study.The sub-protocols are being fast tracked for regulatory approval through the MHRA and subject to approval, the team expects to start the first patient dosing within the next 10 days.
Two of AstraZeneca’s molecules are being explored, one a Bruton’s tyrosine kinase (BTK) inhibitor previously approved for a different indication and the other a Phase II drug candidate targeting interleukin 33 (IL-33), as part of this first wave of potential treatments in the ACCORD platform.
The inclusion of these potential medicines in ACCORD is based on scientific evidence linked to how a hyper-activated immune response may result in pneumonia, respiratory failure and death of patients hospitalised with COVID-19 infections. The Bruton’s tyrosine kinase (BTK) pathway is involved in production of inflammatory cytokines and published data1,2,3,4 suggests that dysregulated BTK-dependent macrophage signaling may be involved in the exaggerated inflammatory responses to SARS-COV-2 and play a role in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). IL-33 is a broad acting damage-response cytokine5 that is released in response to viral infections and tissue damage6 and may play a role in driving and amplifying the overactive inflammatory response in the lungs of patients who are severely ill with COVID-19. The trials will assess how these potential medicines might help alleviate the “cytokine storm” associated with the disease – where the immune system can overreact and attack vital organs like the lungs and the liver.
Where the results of the assessment in ACCORD indicate potential effectiveness and safety of a compound, they are expected to advance rapidly onto large scale trial platforms such as the Randomised Evaluation of COVID Therapy (RECOVERY) trial for further evaluation. Through the Therapeutic Task Force, the life science sector can suggest potential drugs or molecules that could be tested through the ACCORD platform. Data will be open source and freely available to enable global knowledge sharing and collaboration.
With the COVID-19 pandemic claiming thousands of lives daily, defeating COVID-19 requires a collective effort from everyone working in healthcare and we are committed to playing our part. We continue to pay tribute to those working on the frontlines of this pandemic, in the UK and globally.
References
1. Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016; 19:181-93.
2. Huang KJ, Su IJ, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients. J Med Virol. 2005; 75:185-94.
3. Wong CK, Lam CW, Wu AK, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004; 136:95-103.
4. Yoshikawa T, Hill T, Li K, et al. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009; 83:3039-48.
5. Cayrol C, Girard JP. Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev. 2018; 281(1):154-168.
6. Kearley J, Silver JS, Sanden C, Liu Z, Berlin AA, White N, et al. Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection. Immunity. 2015;42(3):566-79.