Combination therapies for COVID‐19: An overview of the clinical trials landscape

Sola Akinbolade; Diarmuid Coughlan; Ross Fairbairn; Glenn McConkey; Helen Powell; Dapo Ogunbayo; Dawn Craig

doi:10.1111/bcp.15089

journal article Oct 17, 2021

Combination therapies for COVID‐19: An overview of the clinical trials landscape

Sola Akinbolade

Diarmuid Coughlan Ross Fairbairn Glenn McConkey Helen Powell Dapo Ogunbayo Dawn Craig

British Journal of Clinical Pharmacology Vol. 88 No. 4 pp. 1590-1597 · Wiley

View at Publisher Save 10.1111/bcp.15089

Abstract

The COVID‐19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS‐CoV‐2 lifecycle and COVID‐19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID‐19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as “pivotal clinical trials” (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data.

Topics

No keywords indexed for this article. Browse by subject →

References

56

[1]

Cucinotta D "WHO declares COVID‐19 a pandemic" Acta Bio Medica: Atenei Parmensis (2020)

[2]

WillanJ KingAJ JefferyK BienzN.Challenges for NHS hospitals during covid‐19 epidemic.2020;368:m1117. 10.1136/bmj.m1117

[3]

10.3892/ijmm.2020.4608

[4]

EggletonJS NagalliS.Highly Active Antiretroviral Therapy (HAART). Treasure Island FL: StatPearls Publishing;2020.

[5]

10.1016/s0140-6736(13)61809-7

[6]

Investigating Different Mechanisms of Action in Combination Therapy for Influenza

Kelli Melville, Thalia Rodriguez, Hana M. Dobrovolny

Frontiers in Pharmacology 10.3389/fphar.2018.01207

[7]

10.7150/ijms.50133

[8]

10.1016/s2589-7500(20)30192-8

[9]

10.1080/13543784.2021.1901883

[10]

National Institute for Health and Care Excellence (NICE): RAPID‐C19.Research to access pathway for investigational drugs for COVID‐19 (RAPID‐C19).2021.https://www.nice.org.uk/covid-19/rapid-c19. Accessed January 28 2021.

[11]

ClinicalTrials.gov.ClinicalTrials.govdatabase.2021.https://clinicaltrials.gov/. Accessed May 17 2021.

[12]

Register ECT.European Union Clinical Trials Register.2021.https://www.clinicaltrialsregister.eu/. Accessed May 17 2021.

[13]

World Health Organisation (WHO).International Clinical Trials Registry Platform (ICTRP).2021.https://ictrptest.azurewebsites.net/Default.aspx. Accessed May 17 2021.

[14]

Law Insider.Pivotal Clinical Trial definition.2021.https://www.lawinsider.com/dictionary/pivotal-clinical-trial. Accessed May 14 2021.

[15]

NIHR Innovation Observatory (NIHRIO).COVID‐19 Therapeutics.2021.http://www.io.nihr.ac.uk/report/covid-19-therapeutics/. Accessed April 30 2021.

[16]

10.1056/nejmoa2022926

[17]

Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

New England Journal of Medicine 10.1056/nejmoa2023184

[18]

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

Bin Cao, Yeming Wang, Danning Wen et al.

New England Journal of Medicine 10.1056/nejmoa2001282

[19]

10.1136/bmj.m3869

[20]

US Food and Drug Administration (FDA).Coronavirus (COVID‐19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine.2020.https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and. Accessed May 17 2021.

[21]

Remdesivir for the Treatment of Covid-19 — Final Report

John H. Beigel, Kay M. Tomashek, Lori E. Dodd et al.

New England Journal of Medicine 10.1056/nejmoa2007764

[22]

US Food and Drug Administration (FDA).FDA Approves First Treatment for COVID‐19.2020.https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19. Accessed March 3 2021.

[23]

US Food and Drug Administration (FDA).Letter of Authorization: EUA for baricitinib (Olumiant) in combination with remdesivir (Veklury) for the treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID‐19).2020.https://www.fda.gov/media/143822/download. Accessed December 15 2020.

[24]

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

Andre C. Kalil, Thomas F. Patterson, Aneesh K. Mehta et al.

New England Journal of Medicine 10.1056/nejmoa2031994

[25]

Roche.Roche provides update on the phase III REMDACTA trial of Actemra/RoActemra plus Veklury in patients with severe COVID‐19 pneumonia.2021.https://www.roche.com/media/releases/med-cor-2021-03-11.htm. Accessed May 17 2021.

[26]

10.1056/nejmoa2033130

[27]

HIV i‐BASE.Monoclonal antibody stopped in ACTIV‐3 study: bamlanivimab shows lack of benefit in people hospitalised with COVID‐19.2020.https://i-base.info/htb/39268Accessed May 18 2021.

[28]

PM Live News.Eli Lilly ends COVID‐19 antibody trial in hospitalised setting other studies continue.2020.http://www.pmlive.com/pharma_news/eli_lilly_ends_covid-19_antibody_trial_in_hospitalised_setting _other_studies_continue_1354817?utm_source=pmlive&utm_medium=email&utm_campaign=pmlive_daily. Accessed March 3 2021.

[29]

Takeda press release.CoVIg‐19 Plasma Alliance Announces Topline Results from NIH‐Sponsored Clinical Trial of Investigational COVID‐19 Hyperimmune Globulin Medicine.2021.https://www.takeda.com/newsroom/newsreleases/2021/covig-19-plasma-alliance-announces-topline-results-from-nih-sponsored-clinical-trial-of-investigational-covid-19-hyperimmune-globulin-medicine/. Accessed August 18 2021.

[30]

WCG CentreWatch.Adaptive COVID‐19 Treatment Trial 3 (ACTT‐3).2021.https://www.centerwatch.com/clinical-trials/listings/249972/adaptive-covid-19-treatment-trial-3-actt-3/. Accessed May 6 2021.

[31]

Favipiravir: A new and emerging antiviral option in COVID-19

Umang Agrawal, Reyma Raju, Zarir F. Udwadia

Medical Journal Armed Forces India 10.1016/j.mjafi.2020.08.004

[32]

Cai Q "Experimental treatment with favipiravir for COVID‐19: an open‐label control study" Engineering (Beijing) (2020)

[33]

10.1038/s41577-021-00542-x

[34]

10.1016/j.cell.2021.02.035

[35]

10.1056/nejmoa2029849

[36]

US Food and Drug Administration (FDA).RE: Emergency Use Authorization 090.2021.https://www.fda.gov/media/147629/download. Accessed May 18 2021.

[37]

10.1001/jama.2021.0202

[38]

US Food and Drug Administration (FDA).Frequently Asked Questions on the Emergency Use Authorization for Bamlanivimab and Etesevimab.2021.https://www.fda.gov/media/145808/download. Accessed April 28 2021.

[39]

10.3389/fimmu.2020.01446

[40]

10.1186/s12967-020-02339-3

[41]

10.1016/j.arcmed.2020.05.009

[42]

10.1073/pnas.2005615117

[43]

10.1016/j.intimp.2020.107018

[44]

10.1093/rheumatology/keaa587

[45]

10.1136/annrheumdis-2020-219174

[46]

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

Wen Zhang, Yan Zhao, Fengchun Zhang et al.

Clinical Immunology 10.1016/j.clim.2020.108393

[47]

US Department of Health and Human Services.Emergency Use Authorization of Medical Products.2017.https://www.fda.gov/media/97321/download. Accessed May 18 2021.

[48]

US Food and Drug Administration (FDA).FDA combating COVID‐19 with therapeutics.2020.https://www.fda.gov/media/136832/download. Accessed December 10 2020.

[49]

European Medicines Agency (EMA).EMA issues advice on use of REGN‐COV2 antibody combination (casirivimab/imdevimab).2021.https://www.ema.europa.eu/en/news/ema-issues-advice-use-regn-cov2-antibody-combination-casirivimab-imdevimab. Accessed May 25 2021.

[50]

10.1126/science.abd0831

Showing 50 of 56 references

Cited By

34

A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein

Ellen Van Damme, Pravien Abeywickrema · 2025

Nature

Accurate and interpretable drug-drug interaction prediction enabled by knowledge subgraph learning

Yaqing Wang, Zaifei Yang · 2024

Communications Medicine

Metrics

34

Citations

56

References

Details

Published: Oct 17, 2021
Vol/Issue: 88(4)
Pages: 1590-1597
License: View

Authors

S

Sola Akinbolade

National Institute for Health Research (NIHR) Innovation Observatory, Population Health Sciences Institute, Faculty of Medical Sciences Newcastle University Newcastle UK

D

Diarmuid Coughlan

National Institute for Health Research (NIHR) Innovation Observatory, Population Health Sciences Institute, Faculty of Medical Sciences Newcastle University Newcastle UK

R

Ross Fairbairn

National Institute for Health Research (NIHR) Innovation Observatory, Population Health Sciences Institute, Faculty of Medical Sciences Newcastle University Newcastle UK

G

Glenn McConkey

Medical Research Council (MRC) – UK Research and Innovation (UKRI)/University of Leeds Leeds UK

H

Helen Powell

National Institute for Health and Care Excellence (NICE) Manchester UK

D

Dapo Ogunbayo

National Institute for Health Research (NIHR) Innovation Observatory, Population Health Sciences Institute, Faculty of Medical Sciences Newcastle University Newcastle UK

D

Dawn Craig

National Institute for Health Research (NIHR) Innovation Observatory, Population Health Sciences Institute, Faculty of Medical Sciences Newcastle University Newcastle UK

Cite This Article

Sola Akinbolade, Diarmuid Coughlan, Ross Fairbairn, et al. (2021). Combination therapies for COVID‐19: An overview of the clinical trials landscape. British Journal of Clinical Pharmacology, 88(4), 1590-1597. https://doi.org/10.1111/bcp.15089

Combination therapies for COVID‐19: An overview of the clinical trials landscape

You May Also Like