View source for Biology:COVID-19 drug development

{{Short description|Preventative and therapeutic medications for COVID-19 infection}}
{{pp-semi-indef|small=yes}}
'''COVID-19 drug development''' is the research process to develop preventative therapeutic [[Medicine:Prescription drug|prescription drug]]s that would alleviate the severity of [[Medicine:COVID-19|coronavirus disease 2019]] (COVID-19). From early 2020 through 2021, several hundred [[Medicine:Pharmaceutical industry|drug companies]], [[Engineering:Biotechnology|biotechnology]] firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of [[Medicine:Preclinical development|preclinical]] or [[Medicine:Phases of clinical research|clinical research]] (506 total candidates in April 2021), with 419 potential COVID-19 drugs in [[Engineering:Clinical trial|clinical trial]]s, as of April 2021.<ref name="biorender">{{cite web |title=COVID-19 vaccine and therapeutics tracker |url=https://biorender.com/covid-vaccine-tracker |publisher=BioRender |access-date=21 June 2021 |date=5 April 2021 |archive-date=3 October 2020 |archive-url=https://web.archive.org/web/20201003151410/https://biorender.com/covid-vaccine-tracker |url-status=live }}</ref>

As early as March 2020, the [[Organization:World Health Organization|World Health Organization]] (WHO),<ref name="kai">{{cite journal | vauthors=Kupferschmidt K, Cohen J | title=WHO launches global megatrial of the four most promising coronavirus treatments | journal=Science Magazine | date=22 March 2020 | url=https://www.science.org/content/article/who-launches-global-megatrial-four-most-promising-coronavirus-treatments | access-date=27 March 2020 | doi=10.1126/science.abb8497 | s2cid=216325781 | archive-date=14 September 2020 | archive-url=https://web.archive.org/web/20200914153130/https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments | url-status=live }}</ref> [[Organization:European Medicines Agency|European Medicines Agency]] (EMA),<ref name="ema3-20">{{cite web |title=First regulatory workshop on COVID-19 facilitates global collaboration on vaccine development |url=https://www.ema.europa.eu/en/news/first-regulatory-workshop-covid-19-facilitates-global-collaboration-vaccine-development |publisher=European Medicines Agency |access-date=21 March 2020 |date=18 March 2020 |archive-date=20 March 2020 |archive-url=https://web.archive.org/web/20200320214052/https://www.ema.europa.eu/en/news/first-regulatory-workshop-covid-19-facilitates-global-collaboration-vaccine-development |url-status=live }}</ref> US [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA),<ref name="fda-covid">{{cite press release |title=Coronavirus (COVID-19) Update: FDA Continues to Facilitate Development of Treatments |url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-facilitate-development-treatments |publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) |access-date=21 March 2020 |date=19 March 2020 |archive-date=20 March 2020 |archive-url=https://web.archive.org/web/20200320213847/https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-facilitate-development-treatments |url-status=live }}</ref> and the Chinese government and drug manufacturers<ref name="china">{{cite web |title=China approves first anti-viral drug against coronavirus Covid-19 |url=https://www.clinicaltrialsarena.com/news/china-approves-favilavir-covid-19/ |publisher=Clinical Trials Arena |access-date=21 March 2020 |date=18 February 2020 |archive-date=21 March 2020 |archive-url=https://web.archive.org/web/20200321032505/https://www.clinicaltrialsarena.com/news/china-approves-favilavir-covid-19/ |url-status=live }}</ref><ref name="bloom">{{cite news |title=Chinese Vaccine Approved for Human Testing at Virus Epicenter |url=https://www.bloomberg.com/news/articles/2020-03-18/chinese-vaccine-approved-for-human-testing-at-virus-epicenter |access-date=21 March 2020 |work=Bloomberg News |date=19 March 2020 |archive-date=21 March 2020 |archive-url=https://web.archive.org/web/20200321032504/https://www.bloomberg.com/news/articles/2020-03-18/chinese-vaccine-approved-for-human-testing-at-virus-epicenter |url-status=live }}</ref> were coordinating with academic and industry researchers to speed development of vaccines, [[Biology:Antiviral drug|antiviral drug]]s, and post-infection therapies.<ref name="dhama">{{cite journal | vauthors = Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, Chaicumpa W | title = COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics | journal = Human Vaccines & Immunotherapeutics | volume = 16 | issue = 6 | pages = 1232–1238 | date = June 2020 | pmid = 32186952 | pmc = 7103671 | doi = 10.1080/21645515.2020.1735227 | doi-access = free }}</ref><ref name="zhang2020">{{cite journal | vauthors = Zhang L, Liu Y | title = Potential interventions for novel coronavirus in China: A systematic review | journal = Journal of Medical Virology | volume = 92 | issue = 5 | pages = 479–490 | date = May 2020 | pmid = 32052466 | pmc = 7166986 | doi = 10.1002/jmv.25707 | doi-access = free }}</ref><ref name="fox">{{cite news |vauthors=Fox M |title=Drug makers are racing to develop immune therapies for Covid-19. Will they be ready in time? |url=https://www.statnews.com/2020/03/19/coronavirus-antibody-therapies-will-they-be-ready-in-time/ |publisher=Stat |access-date=21 March 2020 |date=19 March 2020 |archive-date=22 March 2020 |archive-url=https://web.archive.org/web/20200322000254/https://www.statnews.com/2020/03/19/coronavirus-antibody-therapies-will-they-be-ready-in-time/ |url-status=live }}</ref><ref name="chan">{{cite news |vauthors=Chan M |title=Chinese military scientists ordered to win global race to develop coronavirus vaccine |url=https://www.scmp.com/news/china/military/article/3075843/chinese-military-scientists-ordered-win-global-race-develop |access-date=22 March 2020 |work=South China Morning Post |date=19 March 2020 |archive-date=22 March 2020 |archive-url=https://web.archive.org/web/20200322000251/https://www.scmp.com/news/china/military/article/3075843/chinese-military-scientists-ordered-win-global-race-develop |url-status=live }}</ref> The [[Medicine:International Clinical Trials Registry Platform|International Clinical Trials Registry Platform]] of the WHO recorded 536 clinical studies to develop post-infection therapies for COVID-19 infections,<ref name="coalition">{{cite journal | author = COVID-19 Clinical Research Coalition | title = Global coalition to accelerate COVID-19 clinical research in resource-limited settings | journal = Lancet | volume = 395 | issue = 10233 | pages = 1322–1325 | date = April 2020 | pmid = 32247324 | pmc = 7270833 | doi = 10.1016/s0140-6736(20)30798-4 | doi-access = free }}</ref><ref name="maguire">{{cite journal | vauthors = Maguire BJ, Guérin PJ | title = A living systematic review protocol for COVID-19 clinical trial registrations | journal = Wellcome Open Research | volume = 5 | page = 60 | date = 2 April 2020 | pmid = 32292826 | pmc = 7141164 | doi = 10.12688/wellcomeopenres.15821.1 | doi-access = free }}</ref> with numerous established antiviral compounds for treating other infections under clinical research to be repurposed.<ref name=dhama/><ref name="li">{{cite journal | vauthors = Li G, De Clercq E | title = Therapeutic options for the 2019 novel coronavirus (2019-nCoV) | journal = Nature Reviews. Drug Discovery | volume = 19 | issue = 3 | pages = 149–150 | date = March 2020 | pmid = 32127666 | doi = 10.1038/d41573-020-00016-0 | doi-access = free }}</ref><ref name="Dong">{{cite journal | vauthors = Dong L, Hu S, Gao J | title = Discovering drugs to treat coronavirus disease 2019 (COVID-19) | journal = Drug Discoveries & Therapeutics | volume = 14 | issue = 1 | pages = 58–60 | date = 29 February 2020 | pmid = 32147628 | doi = 10.5582/ddt.2020.01012 | url = https://www.jstage.jst.go.jp/article/ddt/14/1/14_2020.01012/_pdf/-char/en | doi-access = free | access-date = 21 March 2020 | archive-date = 20 March 2020 | archive-url = https://web.archive.org/web/20200320210243/https://www.jstage.jst.go.jp/article/ddt/14/1/14_2020.01012/_pdf/-char/en | url-status = live }}</ref><ref name="Harrison">{{cite journal | vauthors = Harrison C | title = Coronavirus puts drug repurposing on the fast track | journal = Nature Biotechnology | volume = 38 | issue = 4 | pages = 379–381 | date = April 2020 | pmid = 32205870 | doi = 10.1038/d41587-020-00003-1 | s2cid = 213394680 | doi-access =  }}</ref>

In March 2020, the WHO initiated the "SOLIDARITY Trial" in 10 countries, enrolling thousands of people infected with COVID-19 to assess treatment effects of four existing antiviral compounds with the most promise of efficacy.<ref name=kai/><ref name="cheng">{{cite journal | vauthors = Cheng MP, Lee TC, Tan DH, Murthy S | title = Generating randomized trial evidence to optimize treatment in the COVID-19 pandemic | journal = CMAJ | volume = 192 | issue = 15 | pages = E405–E407 | date = April 2020 | pmid = 32336678 | pmc = 7162442 | doi = 10.1503/cmaj.200438 }}</ref> A dynamic, systematic review was established in April 2020 to track the progress of registered clinical trials for COVID-19 vaccine and therapeutic drug candidates.<ref name=maguire/>

Drug development is a multistep process, typically requiring more than five years to assure safety and efficacy of the new compound.<ref name="fda-ddp">{{cite web |title=The Drug Development Process |url=https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process |publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) |access-date=21 March 2020 |date=4 January 2018 |archive-date=22 February 2020 |archive-url=https://web.archive.org/web/20200222182002/https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process |url-status=live }}</ref> <!-- In February 2020, the WHO said it did not expect a vaccine against [[Biology:SARS-CoV-2|SARS-CoV-2]] – the causative virus for COVID-19 – to become available in less than 18 months,<ref name="grenfell" /> and conservative estimates of time needed to prove a safe, effective vaccine is about 12 months (early 2021).<ref name="thanh">{{cite journal | vauthors = Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, Mayhew S | title = The COVID-19 vaccine development landscape | journal = Nature Reviews. Drug Discovery | volume = 19 | issue = 5 | pages = 305–306 | date = May 2020 | pmid = 32273591 | doi = 10.1038/d41573-020-00073-5 }}</ref><ref name="preston" /> --> Several national regulatory agencies, such as the EMA and the FDA, approved procedures to expedite clinical testing.<ref name=fda-covid/><ref name="ema-call">{{cite web |title=Call to pool research resources into large multi-centre, multi-arm clinical trials to generate sound evidence on COVID-19 treatments |url=https://www.ema.europa.eu/en/news/call-pool-research-resources-large-multi-centre-multi-arm-clinical-trials-generate-sound-evidence |publisher=European Medicines Agency |access-date=21 March 2020 |date=19 March 2020 |archive-date=21 March 2020 |archive-url=https://web.archive.org/web/20200321032502/https://www.ema.europa.eu/en/news/call-pool-research-resources-large-multi-centre-multi-arm-clinical-trials-generate-sound-evidence |url-status=live }}</ref> By June 2021, dozens of potential post-infection therapies were in the final stage of human testing – [[Engineering:Clinical trial#Phases|phase III–IV clinical trials]].<ref name="milken">{{cite web|title=COVID-19 vaccine and treatments tracker (Choose vaccines or treatments tab, apply filters to view select data)|url=https://airtable.com/shrSAi6t5WFwqo3GM/tblEzPQS5fnc0FHYR/viwJJuMA1ioIgAcPs?blocks=hide|publisher=Milken Institute|access-date=11 June 2021|date=21 June 2021|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624203214/https://airtable.com/shrSAi6t5WFwqo3GM/tblEzPQS5fnc0FHYR/viwJJuMA1ioIgAcPs?blocks=hide|url-status=live}}</ref>

== Background ==
{{AI4 | image = Drug discovery cycle.svg | annotations = | align = right | image-width = 300 | width = 300 | height = 225 | alt = Drug discovery cycle schematic | caption =}}
[[Medicine:Drug development|Drug development]] is the process of bringing a new infectious disease vaccine or therapeutic drug to the market once a [[Chemistry:Lead compound|lead compound]] has been identified through the process of [[Medicine:Drug discovery|drug discovery]].<ref name=fda-ddp/> It includes laboratory research on microorganisms and animals, filing for regulatory status, such as via the FDA, for an investigational new drug to initiate [[Engineering:Clinical trial|clinical trial]]s on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.<ref name="strovel">{{cite book | vauthors = Strovel J, Sittampalam S, Coussens NP, Hughes M, Inglese J, Kurtz A, Andalibi A, Patton L, Austin C, Baltezor M, Beckloff M | title = Assay Guidance Manual | date = 1 July 2016 | pmid = 22553881 | chapter = Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start-up Companies | publisher = Eli Lilly & Company and the National Center for Advancing Translational Sciences | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK92015/ | access-date = 21 March 2020 | archive-date = 19 April 2020 | archive-url = https://web.archive.org/web/20200419043905/https://www.ncbi.nlm.nih.gov/books/NBK92015/ | url-status = live }}</ref><ref name="taylor">{{cite journal | vauthors = Taylor D |title=The Pharmaceutical Industry and the Future of Drug Development|journal=Issues in Environmental Science and Technology|date=2015|pages=1–33|doi=10.1039/9781782622345-00001 |publisher=Royal Society of Chemistry|isbn=978-1-78262-189-8}}</ref> The entire process – from concept through preclinical testing in the laboratory to clinical trial development, including Phase I–III trials – to approved vaccine or drug normally takes more than a decade.<ref name=fda-ddp/><ref name=strovel/><ref name=taylor/>

The term "preclinical research" is defined by laboratory studies ''[[In vitro|in vitro]]'' and ''[[Biology:In vivo|in vivo]]'', indicating a beginning stage for development of a preventative vaccine, antiviral or other post-infection therapies,<ref name="dhama" /> such as experiments to determine [[Chemistry:Dose (biochemistry)|effective doses]] and [[Medicine:Toxicity|toxicity]] in animals, before a candidate compound is advanced for safety and efficacy evaluation in humans.<ref name="fda-pcr">{{cite web|date=4 January 2018|title=Step 2: Preclinical Research|url=https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research|access-date=23 March 2020|publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|archive-date=16 September 2020|archive-url=https://web.archive.org/web/20200916215856/https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research|url-status=live}}</ref> To complete the preclinical stage of drug development – then be tested for safety and efficacy in an adequate number of people infected with COVID-19 (hundreds to thousands in different countries) – is a process likely to require 1–2 years for COVID-19 therapies, according to several reports in early 2020.<ref name="fox" /><ref name="grenfell">{{cite web|date=14 February 2020|title=Here's why the WHO says a coronavirus vaccine is 18 months away|url=https://theconversation.com/heres-why-the-who-says-a-coronavirus-vaccine-is-18-months-away-131213|access-date=11 November 2020|website=The Conversation|vauthors=Grenfell R, Drew T|archive-date=5 December 2020|archive-url=https://web.archive.org/web/20201205123327/https://theconversation.com/heres-why-the-who-says-a-coronavirus-vaccine-is-18-months-away-131213|url-status=live}}</ref><ref name="preston">{{cite news|date=19 March 2020|title=Why will a coronavirus vaccine take so long?|work=The Boston Globe|url=https://www.bostonglobe.com/2020/03/19/opinion/why-will-coronavirus-vaccine-take-so-long/|access-date=21 March 2020|vauthors=Preston E|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728231320/https://www.bostonglobe.com/2020/03/19/opinion/why-will-coronavirus-vaccine-take-so-long/|url-status=live}}</ref><ref name="Gates">{{cite journal|vauthors=Gates B|date=February 2020|title=Responding to Covid-19 – A Once-in-a-Century Pandemic?|journal=The New England Journal of Medicine|volume=382|issue=18|pages=1677–1679|doi=10.1056/nejmp2003762|pmid=32109012|doi-access=free}}</ref> Despite these efforts, the success rate for drug candidates to reach eventual regulatory approval through the entire drug development process for treating [[Medicine:Infectious disease|infectious disease]]s is only 19%.<ref name="bio" />

Phase I trials test primarily for safety and preliminary dosing in a few dozen healthy subjects, while Phase II trials – following success in Phase I – evaluate therapeutic efficacy against the COVID-19 disease at ascending dose levels (efficacy based on [[Biology:Biomarker|biomarker]]s), while closely evaluating possible [[Medicine:Adverse effect|adverse effect]]s of the candidate therapy (or combined therapies), typically in hundreds of people. A common trial design for Phase II studies of possible COVID-19 drugs is [[Randomized controlled trial|randomized]], [[Medicine:Placebo|placebo]]-controlled, [[Blinded experiment|blinded]], and conducted at multiple sites, while determining more precise, effective doses and monitoring for adverse effects.<ref name="fda-cr2">{{cite web|date=4 January 2018|title=The drug development process: Clinical research|url=https://www.fda.gov/patients/drug-development-process/step-3-clinical-research|access-date=28 April 2020|publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|archive-date=20 June 2020|archive-url=https://web.archive.org/web/20200620235501/https://www.fda.gov/patients/drug-development-process/step-3-clinical-research|url-status=live}}</ref>

The success rate for Phase II trials to advance to Phase III (for all diseases) is about 31%, and for infectious diseases specifically, about 43%.<ref name="bio" /> Depending on its duration (longer more expensive) – typically a period of several months to two years<ref name="fda-cr2" /> – an average-length Phase II trial costs {{USD|57}} million (2013 dollars, including preclinical and Phase I costs).<ref name="dimasi2">{{cite journal|vauthors=DiMasi JA, Grabowski HG, Hansen RW|date=May 2016|title=Innovation in the pharmaceutical industry: New estimates of R&D costs|url=https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/12742/DiMasi-Grabowski-Hansen-RnD-JHE-2016.pdf;sequence=1|journal=Journal of Health Economics|volume=47|pages=20–33|doi=10.1016/j.jhealeco.2016.01.012|pmid=26928437|hdl-access=free|hdl=10161/12742|access-date=24 March 2020|archive-date=14 May 2020|archive-url=https://web.archive.org/web/20200514051624/https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/12742/DiMasi-Grabowski-Hansen-RnD-JHE-2016.pdf|url-status=live}}</ref> Successful completion of a Phase II trial does not reliably forecast that a candidate drug will be successful in Phase III research.<ref name="vannorman2">{{cite journal|vauthors=Van Norman GA|date=June 2019|title=Phase II Trials in Drug Development and Adaptive Trial Design|journal=JACC. Basic to Translational Science|volume=4|issue=3|pages=428–437|doi=10.1016/j.jacbts.2019.02.005|pmc=6609997|pmid=31312766}}</ref>

Phase III trials for COVID-19 involve hundreds-to-thousands of hospitalized participants, and test effectiveness of the treatment to reduce effects of the disease, while monitoring for adverse effects at the optimal dose, such as in the multinational Solidarity and Discovery trials.<ref name="kai" /><ref name="fda-ddp" /><ref name="mullard">{{cite journal|vauthors=Mullard A|date=April 2020|title=Flooded by the torrent: the COVID-19 drug pipeline|journal=Lancet|volume=395|issue=10232|pages=1245–1246|doi=10.1016/S0140-6736(20)30894-1|pmc=7162641|pmid=32305088}}</ref>

==Candidates==
[[Image:Real-time dashboard of clinical trials for COVID-19 Lancet avril 2020.jpg|thumb|upright=1.7|Evidence network of COVID-19 clinical trials of 15 therapeutic candidates.<ref name="thorlund">{{cite journal | vauthors = Thorlund K, Dron L, Park J, Hsu G, Forrest JI, Mills EJ | title = A real-time dashboard of clinical trials for COVID-19 | journal = The Lancet. Digital Health | volume = 2 | issue = 6 | pages = e286–e287 | date = June 2020 | pmid = 32363333 | pmc = 7195288 | doi = 10.1016/S2589-7500(20)30086-8 }}</ref> Circles represent interventions or intervention groups (categories). Lines between two circles indicate comparisons in clinical trials.<ref name="thorlund" />]]{{update section|date=February 2021}}According to one source (as of August 2020), diverse categories of preclinical or early-stage clinical research for developing COVID-19 therapeutic candidates included:<ref name="milken" />
* [[Biology:Antibody|antibodies]] (81 candidates)
* antivirals (31 candidates)
* cell-based compounds (34 candidates)
* [[Biology:RNA|RNA]]-based compounds (6 candidates)
* scanning compounds to be repurposed (18 candidates)
* various other therapy categories, such as anti-inflammatory, [[Medicine:Malaria|antimalarial]], [[Biology:Interferon|interferon]], protein-based, [[Chemistry:Antibiotic|antibiotic]]s, and [[Biology:Receptor (biochemistry)|receptor-modulating]] compounds.<ref name="milken" />
[[Engineering:Clinical trial#Phases|Pivotal Phase III trials]] assess whether a candidate drug has efficacy specifically against a disease, and – in the case of people hospitalized with severe COVID-19 infections – test for an effective dose level of the repurposed or new drug candidate to improve the illness (primarily pneumonia) from COVID-19 infection.<ref name="kai" /><ref name="coalition" /><ref name="acs">{{cite web|url=https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html|title=What are the phases of clinical trials?|publisher=American Cancer Society|date=2020|access-date=4 April 2020|archive-date=6 June 2020|archive-url=https://web.archive.org/web/20200606161152/https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html|url-status=live}}</ref> For an already-approved drug (such as [[Chemistry:Hydroxychloroquine|hydroxychloroquine]] for malaria), [[Medicine:Phases of clinical research#Phase IV|Phase III–IV trials]] determine in hundreds to thousands of COVID-19-infected people the possible extended use of an already-approved drug for treating COVID-19 infection.<ref name="acs" /> As of August 2020, over 500 candidate therapeutics were in preclinical or a stage of Phase I–IV development, with new Phase II–III trials announced for hundreds of therapeutic candidates during 2020.<ref name="milken" />

Numerous candidate drugs under study as "supportive" treatments to relieve discomfort during illness, such as NSAIDs or [[Medicine:Bronchodilator|bronchodilator]]s, are not included in the table below. Others in early-stage Phase II trials or numerous treatment candidates in Phase I trials,<ref name="milken" /> are also excluded. Drug candidates in Phase I–II trials have a low rate of success (under 12%) to pass through all trial phases to gain eventual approval.<ref name="strovel" /><ref name="vannorman2" /> Once having reached Phase III trials, therapeutic candidates for diseases related to COVID-19 infection – [[Medicine:Infectious disease|infectious]] and [[Medicine:Respiratory disease|respiratory disease]]s – have a success rate of about 72%.<ref name="bio">{{cite web|date=June 2016|title=Clinical development success rates: 2006–2015|url=https://www.bio.org/sites/default/files/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf|publisher=BIO Industry Analysis|access-date=21 March 2020|archive-date=1 July 2016|archive-url=https://web.archive.org/web/20160701210803/https://www.bio.org/sites/default/files/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf|url-status=live}}</ref>

{| class="wikitable"
|+ COVID-19: candidate drug treatments in Phase III–IV trials
|-
! Drug candidate
! Description
! Existing disease approval
! Trial sponsor(s)
! Location(s)
! Expected results
! Notes,<br />references
|-
|[[Biology:Remdesivir|Remdesivir]]
|antiviral; [[Chemistry:Adenosine|adenosine]] [[Chemistry:Nucleoside analogue|nucleotide analog]] inhibiting [[Biology:RNA|RNA]] synthesis in [[Biology:Coronavirus|coronavirus]]es
| investigational<ref name="drugs-remdes">{{cite web |title=Remdesivir approval status |url=https://www.drugs.com/history/remdesivir.html |publisher=Drugs.com |access-date=6 April 2020 |date=24 March 2020 |archive-date=19 September 2020 |archive-url=https://web.archive.org/web/20200919022027/https://www.drugs.com/history/remdesivir.html |url-status=live }}</ref>
|[[Company:Gilead Sciences|Gilead]], WHO, INSERM, NIAID
| China, Japan initially; extended internationally in Global Solidarity and Discovery Trials, and US NIAID ACTT Trial
| Mid-2020 (Chinese, Japanese trials)
|<ref name="milken" /><ref name="inserm-disc">{{cite web |title=Launch of a European clinical trial against COVID-19 |url=https://presse.inserm.fr/en/launch-of-a-european-clinical-trial-against-covid-19/38737/ |publisher=INSERM |access-date=5 April 2020 |date=22 March 2020 |quote=The great strength of this trial is its "adaptive" nature. This means that ineffective experimental treatments can very quickly be dropped and replaced by other molecules that emerge from research efforts. We will therefore be able to make changes in real time, in line with the most recent scientific data, in order to find the best treatment for our patients |archive-date=22 May 2020 |archive-url=https://web.archive.org/web/20200522101217/https://presse.inserm.fr/en/launch-of-a-european-clinical-trial-against-covid-19/38737/ |url-status=live }}</ref><ref name="ned">{{cite web |vauthors=Pagliarulo N |title=A closer look at the Ebola drug that's become the top hope for a coronavirus treatment |url=https://www.biopharmadive.com/news/coronavirus-remdesivir-gilead-antiviral-drug-covid-19/573261/ |publisher=BioPharma Dive |access-date=19 March 2020 |date=5 March 2020 |quote=There's only one drug right now that we think may have real efficacy. And that's remdesivir." said Bruce Aylward, a senior advisor and international leader of the World Health Organization's joint mission to China |archive-date=31 October 2021 |archive-url=https://web.archive.org/web/20211031104343/https://www.biopharmadive.com/news/coronavirus-remdesivir-gilead-antiviral-drug-covid-19/573261/ |url-status=live }}</ref> <small>selectively provided by Gilead for COVID-19 emergency access;</small><ref name="remdes-emerg">{{cite web |title=Emergency access to remdesivir outside of clinical trials |url=https://www.gilead.com/purpose/advancing-global-health/covid-19/emergency-access-to-remdesivir-outside-of-clinical-trials |publisher=Gilead Sciences |access-date=7 April 2020 |date=1 April 2020 |archive-date=7 April 2020 |archive-url=https://web.archive.org/web/20200407135421/https://www.gilead.com/purpose/advancing-global-health/covid-19/emergency-access-to-remdesivir-outside-of-clinical-trials |url-status=live }}</ref><ref name="cdc3-21">{{cite web|date=21 March 2020|title=Information for clinicians on therapeutic options for COVID-19 patients|url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html|access-date=22 March 2020|publisher=US Centers for Disease Control and Prevention|archive-date=8 April 2020|archive-url=https://web.archive.org/web/20200408234646/https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html|url-status=live}}</ref> <small>both promising and negative effects reported in April</small><ref name="actt">{{ClinicalTrialsGov|NCT04280705|Adaptive COVID-19 Treatment Trial (ACTT)}}</ref><ref name="fauci">{{cite press release | title = NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19 | date = 29 April 2020 | url = https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 | publisher = US National Institute of Allergy and Infectious Diseases | access-date = 29 April 2020 | archive-date = 30 April 2020 | archive-url = https://web.archive.org/web/20200430085036/https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 | url-status = live }}</ref><ref name="wang">{{cite journal | vauthors = Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, Wang C | title = Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial | journal = Lancet | volume = 395 | issue = 10236 | pages = 1569–1578 | date = May 2020 | pmid = 32423584 | pmc = 7190303 | doi = 10.1016/S0140-6736(20)31022-9 }}</ref>
|-
| [[Chemistry:Hydroxychloroquine|Hydroxychloroquine]] or [[Chemistry:Chloroquine|chloroquine]]
| [[Biology:Antiparasitic|antiparasitic]] and antirheumatic; [[Social:Generic drug|generic]] made by many manufacturers
|[[Medicine:Malaria|malaria]], rheumatoid arthritis, [[Medicine:Systemic lupus erythematosus|lupus]] (International)<ref name="drugs-hydroxy">{{cite web |title=Hydroxychloroquine sulfate |url=https://www.drugs.com/monograph/hydroxychloroquine-sulfate.html |publisher=Drugs.com |access-date=5 April 2020 |date=31 March 2020 |archive-date=20 March 2020 |archive-url=https://web.archive.org/web/20200320234847/https://www.drugs.com/monograph/hydroxychloroquine-sulfate.html |url-status=live }}</ref><ref name="drugs-chlor">{{cite web |title=Chloroquine phosphate |url=https://www.drugs.com/monograph/chloroquine-phosphate.html |publisher=Drugs.com |access-date=5 April 2020 |date=31 March 2020 |archive-date=8 December 2015 |archive-url=https://web.archive.org/web/20151208200339/http://www.drugs.com/monograph/aralen-phosphate.html |url-status=live }}</ref>
| CEPI, WHO, INSERM
| Multiple sites in China; global Solidarity and Discovery Trials
| June 2020 (discontinued by WHO)
|<small>[[Chemistry:Chloroquine#Side effects|multiple side effects]]; possible adverse [[Medicine:Prescription drug|prescription drug]] [[Medicine:Drug interaction|interactions]];</small><ref name="drugs-hydroxy" /><ref name="drugs-chlor" /> <small>discontinued in June from WHO Solidarity trial and UK Recovery trial as "having no clinical benefit in hospitalised patients with COVID-19";<ref name="mulier">{{cite news|date=17 June 2020|title=Hydroxychloroquine halted in WHO-sponsored COVID-19 trials|work=Bloomberg|url=https://www.bloomberg.com/news/articles/2020-06-17/hydroxychloroquine-testing-halted-in-who-sponsored-covid-trial|access-date=17 June 2020|vauthors=Mulier T|archive-date=11 October 2020|archive-url=https://web.archive.org/web/20201011181114/https://www.bloomberg.com/news/articles/2020-06-17/hydroxychloroquine-testing-halted-in-who-sponsored-covid-trial|url-status=live}}</ref><ref name="rec-nobenefit">{{cite web|date=5 June 2020|title=No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19|url=https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19|access-date=7 June 2020|publisher=Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK|archive-date=8 October 2020|archive-url=https://web.archive.org/web/20201008142832/https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19|url-status=live}}</ref> </small> <small>trials</small><ref name="milken" /><ref name="inserm-disc" />
|-
|[[Chemistry:Favipiravir|Favipiravir]]
| antiviral against influenza
| influenza (China)<ref name="drugs-fuji">{{cite web |title=Fujifilm Announces the Start of a Phase III Clinical Trial of Influenza Antiviral Drug Avigan (favipiravir) on COVID-19 in Japan and Commits to Increasing Production |url=https://www.drugs.com/clinical_trials/fujifilm-announces-start-phase-iii-clinical-trial-influenza-antiviral-avigan-favipiravir-covid-19-18505.html |publisher=Drugs.com via Fujifilm Toyama Chemical Co., Ltd |access-date=6 April 2020 |date=31 March 2020 |archive-date=28 July 2020 |archive-url=https://web.archive.org/web/20200728235214/https://www.drugs.com/clinical_trials/fujifilm-announces-start-phase-iii-clinical-trial-influenza-antiviral-avigan-favipiravir-covid-19-18505.html |url-status=live }}</ref>
|[[Company:Fujifilm|Fujifilm]]
| China
| April 2020
|<ref name="milken" /><ref name="zhang2020" /><ref name="gregory">{{cite news |vauthors=Gregory A |title=Coronavirus: Japanese anti-viral drug effective in treating patients, Chinese official says |url=https://www.independent.co.uk/news/world/asia/coronavirus-treatment-anti-viral-drug-favipiravir-avigan-wuhan-china-a9408066.html |access-date=19 March 2020 |work=The Independent |date=18 March 2020 |archive-date=9 October 2020 |archive-url=https://web.archive.org/web/20201009085714/https://www.independent.co.uk/news/world/asia/coronavirus-treatment-anti-viral-drug-favipiravir-avigan-wuhan-china-a9408066.html |url-status=live }}</ref>
|-
| Lopinavir/ritonavir without or with [[Chemistry:Interferon beta-1a|interferon beta-1a]]
| antiviral, immune suppression
| investigational combination; lopinavir/ritonavir approved<ref name="drugs-riton">{{cite web |title=Ritonavir |url=https://www.drugs.com/international/ritonavir.html |publisher=Drugs.com |access-date=6 April 2020 |date=2020 |archive-date=28 July 2020 |archive-url=https://web.archive.org/web/20200728231320/https://www.drugs.com/international/ritonavir.html |url-status=live }}</ref>
| CEPI, WHO, UK Government, Univ. of Oxford, INSERM
| Global Solidarity and Discovery Trials, multiple countries
| mid-2020
|<ref name="milken" /><ref name="inserm-disc" />
|-
|[[Chemistry:Sarilumab|Sarilumab]]
| human [[Biology:Monoclonal antibody|monoclonal antibody]] against [[Biology:Interleukin-6 receptor|interleukin-6 receptor]]
|[[Medicine:Rheumatoid arthritis|rheumatoid arthritis]] (US, Europe)<ref name="drugs-kevz">{{cite web |title=Kevzara |url=https://www.drugs.com/kevzara.html |publisher=Drugs.com |access-date=6 April 2020 |date=7 March 2019 |archive-date=28 July 2020 |archive-url=https://web.archive.org/web/20200728231232/https://www.drugs.com/kevzara.html |url-status=live }}</ref>
|Regeneron-[[Company:Sanofi|Sanofi]]
| Multiple countries
| Spring 2020
|<ref name="milken" /><ref name="staines">{{cite web |vauthors=Staines R |title=Sanofi begins trial of Kevzara against COVID-19 complications |url=https://pharmaphorum.com/news/sanofi-begins-trial-of-kevzara-against-covid-19-complications/ |publisher=PharmaPhorum |access-date=6 April 2020 |date=31 March 2020 |archive-date=17 August 2020 |archive-url=https://web.archive.org/web/20200817173133/https://pharmaphorum.com/news/sanofi-begins-trial-of-kevzara-against-covid-19-complications/ |url-status=live }}</ref>
|-
| ASC-09 + [[Chemistry:Ritonavir|ritonavir]]
| antiviral
| combination not approved; ritonavir approved for [[Biology:HIV|HIV]]<ref name="drugs-riton" />
| Ascletis Pharma
| Multiple sites in China
| Spring 2020
|<ref name="milken" /><ref name="mcgrath">{{cite web |vauthors=McGrath J |title=All the COVID-19 vaccines and treatments currently in clinical trials |url=https://www.digitaltrends.com/health-fitness/coronavirus-covid-19-vaccines-treatments-list/ |publisher=Digital Trends |access-date=6 April 2020 |date=2 April 2020 |archive-date=8 October 2020 |archive-url=https://web.archive.org/web/20201008162143/https://www.digitaltrends.com/health-fitness/coronavirus-covid-19-vaccines-treatments-list/ |url-status=live }}</ref>
|-
|[[Chemistry:Tocilizumab|Tocilizumab]]
| human monoclonal antibody against interleukin-6 receptor
| immunosuppression, rheumatoid arthritis (US, Europe)<ref name="drugs-toc">{{cite web |title=Tocilizumab |url=https://www.drugs.com/mtm/tocilizumab.html |publisher=Drugs.com |access-date=6 April 2020 |date=7 June 2019 |archive-date=8 September 2020 |archive-url=https://web.archive.org/web/20200908210508/https://www.drugs.com/mtm/tocilizumab.html |url-status=live }}</ref>
|[[Company:Genentech|Genentech]]-[[Company:Hoffmann-La Roche|Hoffmann-La Roche]]
| Multiple countries
| mid-2020
|<ref name="milken" /><ref name="slater">{{cite web |vauthors=Slater H |title=FDA approves Phase III clinical trial of tocilizumab for COVID-19 pneumonia |url=https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia |publisher=Cancer Network, MJH Life Sciences |access-date=28 March 2020 |date=26 March 2020 |archive-date=17 June 2020 |archive-url=https://web.archive.org/web/20200617025935/https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia |url-status=live }}</ref> <small>Roche announced in late July that its Phase III trial of tocilizumab for treating pneumonia in hospitalized people with COVID-19 infection was ineffective<ref>{{cite web|date=29 July 2020|title=Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia|url=https://www.roche.com/media/releases/med-cor-2020-07-29.htm|access-date=18 August 2020|publisher=Hoffmann-La Roche|archive-date=9 January 2021|archive-url=https://web.archive.org/web/20210109093737/https://www.roche.com/media/releases/med-cor-2020-07-29.htm|url-status=live}}</ref></small>
|-
| [[Chemistry:Lenzilumab|Lenzilumab]]
| humanized [[Biology:Monoclonal antibody|monoclonal antibody]] for relieving pneumonia
| new drug candidate
| Humanigen, Inc.
| Multiple sites in the United States
| September 2020
|<ref name="milken" /><ref name="lenzilumab">{{ClinicalTrialsGov|NCT04351152|Phase 3 Study to Evaluate Efficacy and Safety of Lenzilumab in Hospitalized Patients With COVID-19 Pneumonia}}</ref>
|-
| [[Chemistry:Dapagliflozin|Dapagliflozin]]
| [[Chemistry:SGLT2 inhibitor|sodium-glucose cotransporter 2 inhibitor]]
| [[Medicine:Hypoglycemia|hypoglycemia]] agent<ref>{{cite web|url=https://medlineplus.gov/druginfo/meds/a614015.html|title=Dapagliflozin: MedlinePlus Drug Information|website=medlineplus.gov|date=20 April 2020|access-date=27 April 2020|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728231111/https://medlineplus.gov/druginfo/meds/a614015.html|url-status=live}}</ref>
| Saint Luke's Mid America Heart Institute, [[Company:AstraZeneca|AstraZeneca]]
| Multiple countries
| December 2020
|<ref name="milken" /><ref name="dare-04350593">{{ClinicalTrialsGov|NCT04350593|Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19)}}</ref>
|-
| CD24Fc
| antiviral immunomodulator against inflammatory response
| new drug candidate
| OncoImmune, Inc.
| Multiple sites in the United States
| 2021
|<ref name="milken" /><ref name="oncoimmune">{{ClinicalTrialsGov|NCT04317040|CD24Fc as a Non-antiviral Immunomodulator in COVID-19 Treatment (SAC-COVID)}}</ref>
|-
| [[Chemistry:Apabetalone|Apabetalone]]
| selective BET inhibitor
| investigational
| Resverlogix Corp
| United States
| 22 March 2022
| <ref name="milken" /><ref>{{cite journal |url=https://clinicaltrials.gov/ct2/show/NCT04894266 |title=An Open-Label Study of Apabetalone in Covid Infection |date=20 May 2021 |website=NIH National Library of Medicine |access-date=24 May 2021 |archive-date=24 May 2021 |archive-url=https://web.archive.org/web/20210524194622/https://clinicaltrials.gov/ct2/show/NCT04894266 |url-status=live }}</ref>
|}

== Repurposed drug candidates ==
[[Medicine:Drug repositioning|Drug repositioning]] (also called drug repurposing) – the investigation of existing drugs for new therapeutic purposes – is one line of scientific research followed to develop safe and effective COVID-19 treatments.<ref name="Harrison" /><ref>{{cite web|date=7 November 2017|title=Repurposing drugs|url=https://ncats.nih.gov/preclinical/repurpose|access-date=26 March 2020|publisher=[[Organization:National Center for Advancing Translational Sciences|National Center for Advancing Translational Sciences]] (NCATS)|archive-date=4 October 2020|archive-url=https://web.archive.org/web/20201004122507/https://ncats.nih.gov/preclinical/repurpose|url-status=live}}</ref> Several existing antiviral medications, previously developed or used as treatments for [[Unsolved:Severe acute respiratory syndrome|Severe acute respiratory syndrome]] (SARS), [[Medicine:Middle East respiratory syndrome|Middle East respiratory syndrome]] (MERS), HIV/AIDS, and [[Medicine:Malaria|malaria]], are being researched as COVID-19 treatments, with some moving into clinical trials.<ref name="li" />

During the COVID-19 pandemic, drug repurposing is the [[Medicine:Clinical research|clinical research]] process of rapidly screening and defining the safety and efficacy of existing drugs already approved for other diseases to be used for people with COVID-19 infection.<ref name="li" /><ref name="Harrison" /><ref name="kruse">{{cite journal|vauthors=Kruse RL|date=31 January 2020|title=Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China|journal=F1000Research|volume=9|page=72|doi=10.12688/f1000research.22211.1|pmc=7029759|pmid=32117569 |doi-access=free }}</ref> In the usual drug development process,<ref name="fda-ddp" /> confirmation of repurposing for new disease treatment would take many years of clinical research – including [[Randomized controlled trial#Disadvantages|pivotal Phase III clinical trials]] – on the candidate drug to assure its safety and efficacy specifically for treating COVID-19 infection.<ref name="li" /><ref name="kruse" /> In the emergency of a growing COVID-19 pandemic, the drug repurposing process was being accelerated during March 2020 to treat people hospitalized with COVID-19.<ref name="kai" /><ref name="li" /><ref name="Harrison" />

Clinical trials using repurposed, generally safe, existing drugs for hospitalized COVID-19 people may take less time and have lower overall costs to obtain endpoints proving safety (absence of serious [[Medicine:Side effect|side effect]]s) and post-infection efficacy, and can rapidly access existing drug [[Supply chain|supply chain]]s for manufacturing and worldwide distribution.<ref name="kai" /><ref name="li" /><ref name="mit">{{cite journal|vauthors=Mitjà O, Clotet B|date=March 2020|title=Use of antiviral drugs to reduce COVID-19 transmission|journal=The Lancet. Global Health|publisher=Elsevier BV|volume=8|issue=5|pages=e639–e640|doi=10.1016/s2214-109x(20)30114-5|pmc=7104000|pmid=32199468}}</ref> In an international effort to capture these advantages, the WHO began in mid-March 2020 expedited international [[Medicine:Phases of clinical research#Phase II|Phase II–III trials]] on four promising treatment options – the SOLIDARITY trial<ref name="kai" /><ref name="un3-18">{{cite news|date=18 March 2020|title=UN health chief announces global 'solidarity trial' to jumpstart search for COVID-19 treatment|work=United Nations – News|agency=World Health Organization|url=https://news.un.org/en/story/2020/03/1059722|access-date=29 March 2020|archive-date=23 March 2020|archive-url=https://web.archive.org/web/20200323101633/https://news.un.org/en/story/2020/03/1059722|url-status=live}}</ref><ref name="kai2">{{cite journal|vauthors=Kupferschmidt K, Cohen J|date=March 2020|title=Race to find COVID-19 treatments accelerates|journal=Science|volume=367|issue=6485|pages=1412–1413|bibcode=2020Sci...367.1412K|doi=10.1126/science.367.6485.1412|pmid=32217705|doi-access=free}}</ref> – with numerous other drugs having potential for repurposing in different disease treatment strategies, such as anti-inflammatory, [[Biology:Corticosteroid|corticosteroid]], antibody, [[Biology:Immune system|immune]], and [[Biology:Growth factor|growth factor]] therapies, among others, being advanced into Phase II or III trials during 2020.<ref name="milken" /><ref name="li" /><ref name="kruse" /><ref name="who-drugs">{{cite web|date=21 March 2020|title=COVID-19 drug development: Landscape analysis of therapeutics (table)|url=https://www.who.int/blueprint/priority-diseases/key-action/Table_of_therapeutics_Appendix_17022020.pdf?ua=1|access-date=29 March 2020|publisher=United Nations, World Health Organization|archive-date=10 September 2020|archive-url=https://web.archive.org/web/20200910181317/https://www.who.int/blueprint/priority-diseases/key-action/Table_of_therapeutics_Appendix_17022020.pdf?ua=1|url-status=live}}</ref>

In March 2020, the United States Centers for Disease Control and Prevention (CDC) issued a physician advisory concerning remdesivir for people hospitalized with [[Medicine:Pneumonia|pneumonia]] caused by COVID-19: "While clinical trials are critical to establish the safety and efficacy of this drug, clinicians without access to a clinical trial may request remdesivir for [[Medicine:Expanded access|compassionate use]] through the manufacturer for patients with clinical pneumonia."<ref name="cdc3-21" />

== Novel antibody drugs ==

=== Convalescent plasma ===
[[File:Convalescent plasma collected during COVID-19 pandemic.jpg|right|thumb|Convalescent plasma collected at a blood donor center during the COVID-19 pandemic.]]
Passive immunization with [[Medicine:Convalescent plasma|convalescent plasma]] or [[Biology:Hyperimmune globulin|hyperimmune serum]] has been proposed as a potential treatment for COVID-19. As of May 2021, there is strong evidence that convalescent plasma treatment is not associated with clinical improvements for people with moderate or severe disease and does not decrease the risk of dying.<ref name=":0">{{cite journal |last1=Piechotta |first1=Vanessa |last2=Iannizzi |first2=Claire |last3=Chai |first3=Khai Li |last4=Valk |first4=Sarah J. |last5=Kimber |first5=Catherine |last6=Dorando |first6=Elena |last7=Monsef |first7=Ina |last8=Wood |first8=Erica M. |last9=Lamikanra |first9=Abigail A. |last10=Roberts |first10=David J. |last11=McQuilten |first11=Zoe |date=20 May 2021 |title=Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review |url= |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=5 |pages=CD013600 |doi=10.1002/14651858.CD013600.pub4 |issn=1469-493X |pmc=8135693 |pmid=34013969}}</ref> The potential for adverse effects associated with convalescent plasma treatment is unknown.<ref name=":0" />

In the United States, the FDA has granted temporary authorization to convalescent plasma (plasma from the blood of people who have recovered from COVID-19, which thus contains antibodies against SARS-CoV-2) as an experimental treatment in cases where the person's life is seriously or immediately threatened.<ref>{{cite web|title=FDA now allows treatment of life-threatening COVID-19 cases using blood from patients who have recovered|url=https://social.techcrunch.com/2020/03/24/fda-now-allows-treatment-of-life-threatening-covid-19-cases-using-blood-from-patients-who-have-recovered/|access-date=9 April 2020|website=TechCrunch|date=24 March 2020 |archive-date=11 October 2020|archive-url=https://web.archive.org/web/20201011115831/https://techcrunch.com/2020/03/24/fda-now-allows-treatment-of-life-threatening-covid-19-cases-using-blood-from-patients-who-have-recovered//|url-status=live}}</ref> As of May 2021, at least 12 randomized controlled trials on the effectiveness of convalescent plasma treatment were published in peer-reviewed medical journals.<ref name=":0" /> In addition, as of May 2021, 100 additional trials were 'ongoing' and 33 studies were reported as 'competed' but not yet published.<ref name=":0" />

Argentina, Brazil, Costa Rica, and Mexico have pursued development of [[Biology:Antiserum|antisera]].<ref name="RevistaFapesp">{{cite web|date=14 December 2020|title=Butantan desenvolve soro contra coronavírus|trans-title=Butantan develops serum against coronavirus|url=https://revistapesquisa.fapesp.br/butantan-desenvolve-soro-contra-coronavirus/|access-date=20 January 2021|work=Revista Pesquisa Fapesp|language=pt|vauthors=Fioravanti C|archive-date=20 January 2021|archive-url=https://web.archive.org/web/20210120175028/https://revistapesquisa.fapesp.br/butantan-desenvolve-soro-contra-coronavirus/|url-status=live}}</ref> Brazil began development of an equine hyperimmune serum, obtained by inoculating [[Biology:Horse|horse]]s with recombinant SARS-CoV-2 spike protein, in mid-2020. A consortium of Instituto Vital Brazil, UFRJ, the [[Organization:Oswaldo Cruz Foundation|Oswaldo Cruz Foundation]] and the D'Or Institute for Research and Education in Rio de Janeiro began preclinical trials in May 2020,<ref>{{cite news|date=4 January 2021|title=Vital Brazil desenvolve soro contra covid-19, mas medicamento ainda não foi testado em humanos|language=pt|trans-title=Vital Brazil develops serum against COVID-19, but drug has yet to be tested in humans|newspaper=O Estado de S. Paulo|url=https://politica.estadao.com.br/blogs/estadao-verifica/vital-brazil-desenvolve-soro-contra-covid-19-mas-medicamento-ainda-nao-foi-testado-em-humanos/|access-date=20 January 2021|vauthors=Monnerat A|archive-date=17 January 2021|archive-url=https://web.archive.org/web/20210117094652/https://politica.estadao.com.br/blogs/estadao-verifica/vital-brazil-desenvolve-soro-contra-covid-19-mas-medicamento-ainda-nao-foi-testado-em-humanos/|url-status=live}}</ref> while [[Organization:Instituto Butantan|Instituto Butantan]] in São Paulo completed animal testing in September.<ref name="RevistaFapesp" /> In December 2020, Argentina granted emergency authorization to CoviFab, a locally developed formulation of equine hyperimmune serum, for use in cases of moderate to severe COVID-19, based on the initial results of a single phase 2/3 trial which suggested reductions in mortality, ICU admission, and mechanical ventilation requirements in patients who received the serum.<ref>{{cite news|date=11 January 2021|title=Argentina aprueba uso de suero equino que reduce en un 45% las muertes por COVID-19|language=es|trans-title=Argentina approves use of equine serum which reduces COVID-19 deaths by 45%|publisher=Deutsche Welle|url=https://www.dw.com/es/argentina-aprueba-uso-de-suero-equino-que-reduce-en-un-45-las-muertes-por-covid-19/a-56193399|access-date=20 January 2021|archive-date=25 January 2021|archive-url=https://web.archive.org/web/20210125151008/https://www.dw.com/es/argentina-aprueba-uso-de-suero-equino-que-reduce-en-un-45-las-muertes-por-covid-19/a-56193399|url-status=live}}</ref><ref name="Clarín">{{cite news|date=17 January 2021|title=Coronavirus: terapistas rechazaron "fuertemente" el uso de suero equino en pacientes graves|language=es|trans-title=Coronavirus: medics "strongly" reject use of equine serum in severe patients|work=Clarín|url=https://www.clarin.com/sociedad/coronavirus-terapistas-rechazaron-uso-suero-equino-cuestionan-anmat_0_TjaKglS9w.html|access-date=20 January 2021|archive-date=17 January 2021|archive-url=https://web.archive.org/web/20210117165348/https://www.clarin.com/sociedad/coronavirus-terapistas-rechazaron-uso-suero-equino-cuestionan-anmat_0_TjaKglS9w.html|url-status=live}}</ref> This was harshly criticized by the Argentine Intensive Care Society, which stated that the trial failed to achieve its primary or secondary endpoints and did not demonstrate any [[Statistical significance|statistically significant]] differences between the serum and placebo groups.<ref name="Clarín" />

=== Bamlanivimab/etesevimab ===
{{Excerpt|Bamlanivimab/etesevimab}}

=== Bebtelovimab ===
{{Excerpt|Bebtelovimab}}

=== Casirivimab/imdevimab ===
{{Excerpt|Casirivimab/imdevimab}}

=== Regdanvimab ===
{{Excerpt|Regdanvimab}}

=== Sotrovimab ===
{{Excerpt|Sotrovimab}}

=== Tixagevimab/cilgavimab ===
{{Excerpt|Tixagevimab/cilgavimab}}

=== Vilobelimab ===
{{Excerpt|Vilobelimab}}

== Novel viral replication inhibitors ==
=== Molnupiravir ===
{{Excerpt|Molnupiravir}}

== Novel protease inhibitors ==
=== Ensitrelvir ===
{{Excerpt|Ensitrelvir}}

=== Nirmatrelvir/ritonavir ===
{{Excerpt|Nirmatrelvir/ritonavir}}

== Other ==
=== Sabizabulin ===
{{Excerpt|Sabizabulin}}

== Planning and coordination ==

=== Early planning ===
Over 2018–20, new initiatives to stimulate vaccine and antiviral drug development included partnerships between governmental organizations and industry, such as the European [[Medicine:Innovative Medicines Initiative|Innovative Medicines Initiative]],<ref name="imi">{{cite web|date=2020|title=About the Innovative Medicines Initiative|url=https://www.imi.europa.eu/about-imi|access-date=24 January 2020|publisher=European Innovative Medicines Initiative|archive-date=2 September 2020|archive-url=https://web.archive.org/web/20200902102613/https://www.imi.europa.eu/about-imi|url-status=live}}</ref> the US ''Critical Path Initiative'' to enhance innovation of drug development,<ref>{{cite web|date=23 April 2018|title=Critical Path Initiative|url=https://www.fda.gov/science-research/science-and-research-special-topics/critical-path-initiative|access-date=24 January 2020|publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|archive-date=17 September 2020|archive-url=https://web.archive.org/web/20200917081502/https://www.fda.gov/science-research/science-and-research-special-topics/critical-path-initiative|url-status=live}}</ref> and the ''Breakthrough Therapy'' designation to expedite development and regulatory review of promising candidate drugs.<ref>{{cite web|date=4 January 2018|title=Breakthrough Therapy|url=https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy|access-date=24 January 2020|publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|archive-date=25 September 2020|archive-url=https://web.archive.org/web/20200925120247/https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy|url-status=live}}</ref> To accelerate refinement of [[Medicine:Medical diagnosis|diagnostics]] for detecting COVID-19 infection, a global diagnostic pipeline tracker was formed.<ref name="find">{{cite web|date=2020|title=SARS-CoV-2 Diagnostic Pipeline|url=https://www.finddx.org/covid-19/pipeline/|access-date=4 April 2020|publisher=Foundation for Innovative New Diagnostics|archive-date=16 September 2020|archive-url=https://web.archive.org/web/20200916134705/https://www.finddx.org/covid-19/pipeline/|url-status=live}}</ref>

According to a tracker of clinical trial progress on potential therapeutic drugs for COVID-19 infections, 29 Phase II–IV efficacy trials were concluded in March 2020 or scheduled to provide results in April from hospitals in China – which experienced the first outbreak of COVID-19 in late 2019.<ref name="milken" /> Seven trials were evaluating repurposed drugs already approved to treat [[Medicine:Malaria|malaria]], including four studies on hydroxychloroquine or chloroquine phosphate.<ref name="milken" /> Repurposed antiviral drugs make up most of the Chinese research, with 9 Phase III trials on remdesivir across several countries due to report by the end of April.<ref name="milken" /> Other potential therapeutic candidates under pivotal clinical trials concluding in March–April are vasodilators, [[Biology:Corticosteroid|corticosteroid]]s, [[Medicine:Immunotherapy|immune therapies]], [[Chemistry:Lipoic acid|lipoic acid]], [[Chemistry:Bevacizumab|bevacizumab]], and [[Biology:Recombinant DNA|recombinant]] [[Biology:Angiotensin-converting enzyme 2|angiotensin-converting enzyme 2]], among others.

The COVID-19 Clinical Research Coalition has goals to 1) facilitate [[Rapid reviews|rapid reviews]] of clinical trial proposals by [[Social:Ethics committee|ethics committee]]s and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data, and 4) facilitate sharing of clinical trial outcomes before publication.<ref name="coalition" /> A dynamic review of clinical development for COVID-19 vaccine and drug candidates was in place, as of April.<ref name="maguire" />

By March 2020, the international [[Organization:Coalition for Epidemic Preparedness Innovations|Coalition for Epidemic Preparedness Innovations]] (CEPI) committed to research investments of US$100 million across several countries,<ref name="kelland">{{cite news|date=10 March 2020|title=Epidemic response group ups coronavirus vaccine funding to $23.7 million|work=Reuters|url=https://www.reuters.com/article/us-health-coronavirus-vaccines-cepi/epidemic-response-group-ups-coronavirus-vaccine-funding-to-23-7-million-idUSKBN20X1PO|access-date=21 March 2020|vauthors=Kelland K|archive-date=18 August 2020|archive-url=https://web.archive.org/web/20200818225558/https://www.reuters.com/article/us-health-coronavirus-vaccines-cepi/epidemic-response-group-ups-coronavirus-vaccine-funding-to-23-7-million-idUSKBN20X1PO|url-status=live}}</ref> and issued an urgent call to raise and rapidly invest $2 billion for vaccine development.<ref name="cepi-fund1">{{cite web|date=1 March 2020|title=CEPI's response to COVID-19|url=https://cepi.net/covid-19/|access-date=25 March 2020|publisher=Coalition for Epidemic Preparedness Innovation, Oslo, Norway|archive-date=25 March 2020|archive-url=https://web.archive.org/web/20200325155927/https://cepi.net/covid-19/|url-status=live}}</ref> Led by the Bill and Melinda Gates Foundation with partners investing {{USD|125}} million and coordinating with the World Health Organization, the COVID-19 Therapeutics Accelerator began in March, facilitating drug development researchers to rapidly identify, assess, develop, and [[Scalability|scale up]] potential treatments.<ref name="bmgf">{{cite web|date=10 March 2020|title=COVID-19 Therapeutics Accelerator: Bill & Melinda Gates Foundation, Wellcome, and Mastercard Launch Initiative to Speed Development and Access to Therapies for COVID-19|url=https://www.gatesfoundation.org/Media-Center/Press-Releases/2020/03/COVID-19-Therapeutics-Accelerator|access-date=4 April 2020|publisher=Bill and Melinda Gates Foundation|archive-date=6 October 2020|archive-url=https://web.archive.org/web/20201006215559/https://www.gatesfoundation.org/Media-Center/Press-Releases/2020/03/COVID-19-Therapeutics-Accelerator|url-status=live}}</ref> The COVID-19 Clinical Research Coalition formed to coordinate and expedite results from international clinical trials on the most promising post-infection treatments.<ref name="coalition" /> In early 2020, numerous established antiviral compounds for treating other infections were being repurposed or developed in new clinical research efforts to alleviate the illness of COVID-19.<ref name="dhama" /><ref name="li" /><ref name="milken" />

During March 2020, the [[Organization:Coalition for Epidemic Preparedness Innovations|Coalition for Epidemic Preparedness Innovations]] (CEPI) initiated an international COVID-19 vaccine development fund, with the goal to raise {{USD|2 billion}} for vaccine research and development,<ref name="cepi-fund2">{{cite web|date=6 March 2020|title=CEPI welcomes UK Government's funding and highlights need for $2 billion to develop a vaccine against COVID-19|url=https://cepi.net/news_cepi/2-billion-required-to-develop-a-vaccine-against-the-covid-19-virus/|access-date=23 March 2020|publisher=Coalition for Epidemic Preparedness Innovations, Oslo, Norway|archive-date=22 March 2020|archive-url=https://web.archive.org/web/20200322170547/https://cepi.net/news_cepi/2-billion-required-to-develop-a-vaccine-against-the-covid-19-virus/|url-status=live}}</ref> and committed to investments of {{USD|100 million}} in vaccine development across several countries.<ref name="kelland" /> The Canadian government announced {{CAD|275 million}} in funding for 96 research projects on medical countermeasures against COVID-19, including numerous vaccine candidates at Canadian universities,<ref name="can-funding">{{cite web|date=23 March 2020|title=Government of Canada funds 49 additional COVID-19 research projects – Details of the funded projects|url=https://www.canada.ca/en/institutes-health-research/news/2020/03/government-of-canada-funds-49-additional-covid-19-research-projects-details-of-the-funded-projects.html|access-date=23 March 2020|publisher=Government of Canada|archive-date=22 March 2020|archive-url=https://web.archive.org/web/20200322163807/https://www.canada.ca/en/institutes-health-research/news/2020/03/government-of-canada-funds-49-additional-covid-19-research-projects-details-of-the-funded-projects.html|url-status=live}}</ref><ref name="abedi">{{cite news|date=23 March 2020|title=Canada to spend $192M on developing COVID-19 vaccine|work=Global News|url=https://globalnews.ca/news/6717883/coronavirus-canada-vaccine-spending/|access-date=24 March 2020|vauthors=Abedi M|archive-date=9 April 2020|archive-url=https://web.archive.org/web/20200409200638/https://globalnews.ca/news/6717883/coronavirus-canada-vaccine-spending/|url-status=live}}</ref> with plans to establish a "vaccine bank" of new vaccines for implementation if another COVID-19 outbreak occurs.<ref name="abedi" /><ref name="ctv3-31">{{cite news|date=31 March 2020|title=Vaccine watch: These are the efforts being made around the world|work=CTV News|url=https://www.ctvnews.ca/health/coronavirus/vaccine-watch-these-are-the-efforts-being-made-around-the-world-1.4875920|access-date=1 April 2020|vauthors=O'Brien C|archive-date=24 September 2020|archive-url=https://web.archive.org/web/20200924012154/https://www.ctvnews.ca/health/coronavirus/vaccine-watch-these-are-the-efforts-being-made-around-the-world-1.4875920|url-status=live}}</ref> The Bill & Melinda Gates Foundation invested {{USD}}150 million in April for development of COVID-19 vaccines, diagnostics, and therapeutics.<ref>{{cite web|date=15 April 2020|title=Gates Foundation Expands Commitment to COVID-19 Response, Calls for International Collaboration|url=https://www.gatesfoundation.org/Media-Center/Press-Releases/2020/04/Gates-Foundation-Expands-Commitment-to-COVID-19-Response-Calls-for-International-Collaboration|access-date=27 April 2020|publisher=Bill & Melinda Gates Foundation|archive-date=14 September 2020|archive-url=https://web.archive.org/web/20200914174557/https://www.gatesfoundation.org/Media-Center/Press-Releases/2020/04/Gates-Foundation-Expands-Commitment-to-COVID-19-Response-Calls-for-International-Collaboration|url-status=live}}</ref>

====Computer-assisted research====
In March 2020, the United States Department of Energy, [[Organization:National Science Foundation|National Science Foundation]], [[Organization:NASA|NASA]], industry, and nine universities pooled resources to access supercomputers from [[Company:IBM|IBM]], combined with cloud computing resources from [[Company:Hewlett Packard Enterprise|Hewlett Packard Enterprise]], [[Company:Amazon|Amazon]], [[Company:Microsoft|Microsoft]], and [[Company:Google|Google]], for drug discovery.<ref name="Summit">{{cite news|date=23 March 2020|title=Sixteen supercomputers tackle coronavirus cures in the US|work=CNET|publisher=ViacomCBS|url=https://www.cnet.com/news/sixteen-supercomputers-tackle-coronavirus-cures-in-us/|access-date=27 April 2020|vauthors=Shankland S|archive-date=20 September 2020|archive-url=https://web.archive.org/web/20200920070800/https://www.cnet.com/news/sixteen-supercomputers-tackle-coronavirus-cures-in-us/|url-status=live}}</ref><ref name="C-19HPCC">{{cite web|date=2020|title=The COVID-19 High Performance Computing Consortium|url=https://covid19-hpc-consortium.org/|access-date=27 April 2020|publisher=The COVID-19 High Performance Computing Consortium|archive-date=23 September 2020|archive-url=https://web.archive.org/web/20200923003850/https://covid19-hpc-consortium.org/|url-status=live}}</ref> The COVID-19 High Performance Computing Consortium also aims to forecast disease spread, model possible vaccines, and screen thousands of chemical compounds to design a COVID-19 vaccine or therapy.<ref name="Summit" /><ref name="C-19HPCC" /> The Consortium used up 437 peta[[FLOPS]] of computing power by May 2020.<ref name="Wiggers">{{cite news |last1=Wiggers |first1=Kyle |title=COVID-19 HPC Consortium pours 437 petaflops of compute power toward virus research |url=https://venturebeat.com/2020/05/28/covid-19-hpc-consortium-pours-437-petaflops-of-compute-power-toward-virus-research/ |access-date=1 April 2022 |work=VentureBeat |date=28 May 2020 |archive-date=26 March 2022 |archive-url=https://web.archive.org/web/20220326052834/https://venturebeat.com/2020/05/28/covid-19-hpc-consortium-pours-437-petaflops-of-compute-power-toward-virus-research/ |url-status=live }}</ref>

The C3.ai Digital Transformation Institute, an additional consortium of Microsoft, six universities (including the [[Organization:Massachusetts Institute of Technology|Massachusetts Institute of Technology]], a member of the first consortium), and the National Center for Supercomputer Applications in Illinois, working under the auspices of C3.ai, an artificial intelligence software company, are pooling supercomputer resources toward drug discovery, medical protocol development and public health strategy improvement, as well as awarding large grants to researchers who proposed by May to use AI to carry out similar tasks.<ref name="C3NewsRelease">{{cite web|date=26 March 2020|title=C3.ai, Microsoft, and Leading Universities Launch C3.ai Digital Transformation Institute|url=https://c3.ai/c3-ai-microsoft-and-leading-universities-launch-c3-ai-digital-transformation-institute/|access-date=27 April 2020|website=C3.ai|archive-date=14 August 2020|archive-url=https://web.archive.org/web/20200814095922/https://c3.ai/c3-ai-microsoft-and-leading-universities-launch-c3-ai-digital-transformation-institute/|url-status=live}}</ref><ref name="NYTBroad">{{cite news|date=26 March 2020|title=A.I. Versus the Coronavirus|work=The New York Times|url=https://www.nytimes.com/2020/03/26/science/ai-versus-the-coronavirus.html|access-date=27 April 2020|vauthors=Broad W|archive-date=31 August 2020|archive-url=https://web.archive.org/web/20200831083614/https://www.nytimes.com/2020/03/26/science/ai-versus-the-coronavirus.html|url-status=live}}</ref>

In March 2020, the [[Distributed computing|distributed computing]] project [[Medicine:Folding@home|Folding@home]] launched a program to assist drug developers, initially simulating protein targets from SARS-CoV-2 and the related SARS-CoV virus, which has been studied previously.<ref name="tomshw-fah">{{cite web|date=3 March 2020|title=Help Cure Coronavirus with Your PC's Leftover Processing Power|url=https://www.tomshardware.com/news/folding-fight-coronavirus|access-date=12 March 2020|website=Tom's Hardware|vauthors=Broekhuijsen N|archive-date=21 August 2020|archive-url=https://web.archive.org/web/20200821001025/https://www.tomshardware.com/news/folding-fight-coronavirus|url-status=live}}</ref><ref name="fah-newspost">{{cite web|date=27 February 2020|title=Folding@home takes up the fight against COVID-19 / 2019-nCoV|url=https://foldingathome.org/2020/02/27/foldinghome-takes-up-the-fight-against-covid-19-2019-ncov/|access-date=12 March 2020|website=Folding@home|vauthors=Bowman G|archive-date=15 March 2020|archive-url=https://web.archive.org/web/20200315194201/https://foldingathome.org/2020/02/27/foldinghome-takes-up-the-fight-against-covid-19-2019-ncov/|url-status=live}}</ref><ref>{{cite web|date=16 March 2020|title=Folding@home Turns Its Massive Crowdsourced Computer Network Against COVID-19|url=https://www.hpcwire.com/2020/03/16/foldinghome-turns-its-massive-crowdsourced-computer-network-against-covid-19/|access-date=27 April 2020|archive-date=8 September 2020|archive-url=https://web.archive.org/web/20200908111509/https://www.hpcwire.com/2020/03/16/foldinghome-turns-its-massive-crowdsourced-computer-network-against-covid-19/|url-status=live}}</ref><ref name="Masterson">{{cite news |last1=Masterson |first1=Victoria |title=Your computer can help scientists find a cure for COVID-19. Here's how |url=https://www.weforum.org/agenda/2020/12/citizen-scientists-crowdsourcing-covid-19-cure/ |access-date=1 April 2022 |work=World Economic Forum |date=22 December 2020 |archive-date=5 November 2021 |archive-url=https://web.archive.org/web/20211105182155/https://www.weforum.org/agenda/2020/12/citizen-scientists-crowdsourcing-covid-19-cure/ |url-status=live }}</ref><ref>{{cite web |title=Together We Are Powerful |url=https://foldingathome.org/?lng=en-US |website=FOLDINGATHOME |access-date=1 April 2022 |archive-date=23 March 2022 |archive-url=https://web.archive.org/web/20220323080510/https://foldingathome.org/?lng=en-US |url-status=live }}</ref><ref name="Calmiano">{{cite journal |last1=von Delft |first1=Frank |last2=Calmiano |first2=Mark |last3=Chodera |first3=John |last4=Griffen |first4=Ed |last5=Lee |first5=Alpha |last6=London |first6=Nir |last7=Matviuk |first7=Tatiana |last8=Perry |first8=Ben |last9=Robinson |first9=Matt |last10=von Delft |first10=Annette |title=A white-knuckle ride of open COVID drug discovery |journal=Nature |date=June 2021 |volume=594 |issue=7863 |pages=330–332 |doi=10.1038/d41586-021-01571-1 |pmid=34127864 |bibcode=2021Natur.594..330V |s2cid=235438395 |language=en |doi-access=free }}</ref>

Distributed computing project [[Rosetta@home]] also joined the effort in March. The project uses computers of volunteers to model SARS-CoV-2 virus proteins to discover possible drug targets or create new proteins to neutralize the virus. Researchers revealed that with the help of Rosetta@home, they had been able to "accurately predict the atomic-scale structure of an important coronavirus protein weeks before it could be measured in the lab."<ref>{{cite web|date=24 March 2020|title=Rosetta@home Rallies a Legion of Computers Against the Coronavirus|url=https://www.hpcwire.com/2020/03/24/rosettahome-rallies-a-legion-of-computers-against-the-coronavirus/|access-date=4 November 2020|website=HPCwire|language=en-US|archive-date=9 April 2020|archive-url=https://web.archive.org/web/20200409200450/https://www.hpcwire.com/2020/03/24/rosettahome-rallies-a-legion-of-computers-against-the-coronavirus/|url-status=live}}</ref>

In May 2020, the OpenPandemics – COVID-19 partnership between [[Organization:Scripps Research|Scripps Research]] and IBM's [[World Community Grid]] was launched. The partnership is a distributed computing project that "will automatically run a simulated experiment in the background [of connected home PCs] which will help predict the effectiveness of a particular chemical compound as a possible treatment for COVID-19".<ref name="WCG_1">{{cite web|date=2020|title=OpenPandemics – COVID-19|url=https://www.worldcommunitygrid.org/research/opn1/overview.do|access-date=18 May 2020|publisher=IBM|archive-date=17 August 2020|archive-url=https://web.archive.org/web/20200817041601/https://www.worldcommunitygrid.org/research/opn1/overview.do|url-status=live}}</ref>

===International Solidarity and Discovery Trials===
In March, the World Health Organization (WHO) launched the coordinated "Solidarity Trial" in 10 countries on five [[Earth:Continent|continent]]s to rapidly assess in thousands of COVID-19 infected people the potential efficacy of existing antiviral and [[Chemistry:Anti-inflammatory|anti-inflammatory]] agents not yet evaluated specifically for COVID-19 illness.<ref name="kai" /><ref name="cheng" /> By late April, hospitals in over 100 countries were involved in the trial.<ref name="who-st2">{{cite web|date=27 April 2020|title='Solidarity' clinical trial for COVID-19 treatment|url=https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments|access-date=1 May 2020|publisher=World Health Organization|archive-date=12 October 2020|archive-url=https://web.archive.org/web/20201012062825/https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments|url-status=live}}</ref>

The individual or combined drugs undergoing initial studied are 1) [[Chemistry:Lopinavir|lopinavir]]–[[Chemistry:Ritonavir|ritonavir]] combined, 2) lopinavir–ritonavir combined with interferon-beta, 3) [[Biology:Remdesivir|remdesivir]] or 4) (hydroxy)[[Chemistry:Chloroquine|chloroquine]] in separate trials and hospital sites internationally.<ref name="kai" /><ref name="cheng" /> Following a study published by The Lancet on safety concerns with hydroxychloroquine, the WHO suspended use of it from the Solidarity trial in May 2020,<ref name="who-suspend2">{{cite web|date=25 May 2020|title=WHO Director-General's opening remarks at the media briefing on COVID-19|url=https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---25-may-2020|access-date=27 May 2020|publisher=World Health Organization|archive-date=10 October 2020|archive-url=https://web.archive.org/web/20201010190032/https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---25-may-2020|url-status=live}}</ref><ref name="cheng22">{{cite news|vauthors=Cheng M, Keaten J |date=25 May 2020|title=WHO pauses hydroxychloroquine coronavirus trial over safety concerns|work=Global News|publisher=The Associated Press|url=https://globalnews.ca/news/6983283/who-hydroxychloroquine-trial/|access-date=27 May 2020|archive-date=19 September 2020|archive-url=https://web.archive.org/web/20200919045818/https://globalnews.ca/news/6983283/who-hydroxychloroquine-trial/|url-status=live}}</ref> reinstated it after the research was retracted,<ref>{{cite news|date=4 June 2020|title=WHO restarts HCQ trial after Lancet concern over paper that trashed it|website=indianexpress.com|publisher=The Indian Express|url=https://indianexpress.com/article/coronavirus/who-hydroxychloroquine-trail-restart-lancet-6441507/|quote=When contacted, Soumya Swaminathan, chief scientist at WHO, told The Indian Express: Our data safety monitoring board reviewed the mortality data in Solidarity... They did not have concerns related to mortality between HCQ and standard of care. Hence, we have decided to resume the trial.|vauthors=Abantika G, Mascarenhas A|access-date=16 June 2020|archive-date=29 July 2020|archive-url=https://web.archive.org/web/20200729022442/https://indianexpress.com/article/coronavirus/who-hydroxychloroquine-trail-restart-lancet-6441507/|url-status=live}}</ref> then abandoned further use of the drug for COVID-19 treatment when analysis showed in June that it provided no benefit.<ref name="mulier" />

With about 15% of people infected by COVID-19 having severe illness, and hospitals being overwhelmed during the pandemic, WHO recognized a rapid clinical need to test and repurpose these drugs as agents already approved for other diseases and recognized as safe.<ref name="kai" /> The Solidarity project is designed to give rapid insights to key clinical questions:<ref name="kai" /><ref name="stat3-182">{{cite web|date=18 March 2020|title=WHO to launch multinational trial to jumpstart search for coronavirus drugs|url=https://www.statnews.com/2020/03/18/who-to-launch-multinational-trial-to-jumpstart-search-for-coronavirus-drugs/|access-date=28 March 2020|publisher=STAT|vauthors=Branswell H|archive-date=11 October 2020|archive-url=https://web.archive.org/web/20201011053329/https://www.statnews.com/2020/03/18/who-to-launch-multinational-trial-to-jumpstart-search-for-coronavirus-drugs/|url-status=live}}</ref>
* Do any of the drugs reduce mortality?
* Do any of the drugs reduce the time a patient is hospitalized?
* Do the treatments affect the need for people with COVID-19-induced pneumonia to be ventilated or maintained in [[Medicine:Intensive care medicine|intensive care]]?
* Could such drugs be used to minimize the illness of COVID-19 infection in [[Medicine:Health professional|healthcare staff]] and people at high risk of developing severe illness?

Enrolling people with COVID-19 infection is simplified by using data entries, including [[Philosophy:Informed consent|informed consent]], on a WHO website. After the trial staff determines the drugs available at the hospital, the WHO website [[Randomized controlled trial|randomizes]] the hospitalized subject to one of the trial drugs or to the hospital standard of care for treating COVID-19. The trial physician records and submits follow-up information about the subject status and treatment, completing data input via the WHO Solidarity website. The design of the Solidarity trial is not [[Blinded experiment#Terminology|double-blind]] – which is normally the standard in a high-quality clinical trial – but the WHO needed speed with quality for the trial across many hospitals and countries.<ref name="kai" /> A global [[Medicine:Monitoring in clinical trials#Safety monitoring|safety monitoring board of WHO physicians]] examine [[Engineering:Clinical trial#Types|interim results]] to assist decisions on safety and effectiveness of the trial drugs, and alter the trial design or recommend an effective therapy.<ref name="kai" /><ref name="stat3-182" /> A similar web-based study to Solidarity, called "Discovery", was initiated in March across seven countries by INSERM ([[Place:Paris|Paris, France]]).<ref name="kai" /><ref name="inserm-disc" />

The Solidarity trial seeks to implement coordination across hundreds of hospital sites in different countries – including those with poorly-developed infrastructure for clinical trials – yet needs to be conducted rapidly. According to John-Arne Røttingen, chief executive of the Research Council of Norway and chairman of the Solidarity trial international [[Organization:Committee|steering committee]], the trial would be considered effective if therapies are determined to "reduce the proportion of patients that need ventilators by, say, 20%, that could have a huge impact on our national health-care systems."<ref name="mullard" />

During March, funding for the Solidarity trial reached {{US$|108}} million from 203,000 individuals, organizations and governments, with 45 countries involved in financing or trial management.<ref name="who-suspend2" />

A clinical trial design in progress may be modified as an "adaptive design" if accumulating data in the trial provide early insights about positive or negative efficacy of the treatment.<ref name="fda-adaptive">{{cite web|date=1 November 2019|title=Adaptive Designs for Clinical Trials of Drugs and Biologics: Guidance for Industry|url=https://www.fda.gov/media/78495/download|access-date=3 April 2020|website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|format=PDF|archive-date=13 December 2019|archive-url=https://web.archive.org/web/20191213234438/https://www.fda.gov/media/78495/download|url-status=live}}</ref><ref name="pallmann">{{cite journal |vauthors=Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Odondi L, Sydes MR, Villar SS, Wason JM, Weir CJ, Wheeler GM, Yap C, Jaki T|date=February 2018|title=Adaptive designs in clinical trials: why use them, and how to run and report them|journal=BMC Medicine|volume=16|issue=1|page=29|doi=10.1186/s12916-018-1017-7|pmc=5830330|pmid=29490655 |doi-access=free }}</ref> The global Solidarity and European Discovery trials of hospitalized people with severe COVID-19 infection apply adaptive design to rapidly alter trial parameters as results from the four experimental therapeutic strategies emerge.<ref name="coalition" /><ref name="inserm-disc" /><ref name="miller">{{cite news|date=19 March 2020|title=WHO beginning Covid-19 therapy trial|work=Technology News: Science and Enterprise|url=https://sciencebusiness.technewslit.com/?p=38676|access-date=7 April 2020|vauthors=Kotok A|archive-date=9 August 2020|archive-url=https://web.archive.org/web/20200809082955/https://sciencebusiness.technewslit.com/?p=38676|url-status=live}}</ref> Adaptive designs within ongoing Phase II–III clinical trials on candidate therapeutics may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, and coordinating design changes for a specific trial across its international locations.<ref name="vannorman2" /><ref name="pallmann" /><ref name="sato">{{cite journal|vauthors=Sato A, Shimura M, Gosho M|date=April 2018|title=Practical characteristics of adaptive design in Phase 2 and 3 clinical trials|journal=Journal of Clinical Pharmacy and Therapeutics|volume=43|issue=2|pages=170–180|doi=10.1111/jcpt.12617|pmid=28850685|s2cid=3704071|doi-access=free}}</ref>

===Adaptive COVID-19 Treatment Trial===
The US [[Organization:National Institute of Allergy and Infectious Diseases|National Institute of Allergy and Infectious Diseases]] (NIAID) initiated an adaptive design, international Phase III trial (called "ACTT") to involve up to 800 hospitalized COVID-19 people at 100 sites in multiple countries. Beginning with use of remdesivir as the primary treatment over 29 days, the trial definition of its adaptive protocol states that "there will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s)."<ref name="actt" />

=== Operation Warp Speed ===
{{Excerpt|Operation Warp Speed|hat=no}}

=== RECOVERY Trial ===
{{Main article|Medicine:RECOVERY Trial}}
A large-scale, [[Randomized controlled trial|randomized controlled trial]] named the [[Medicine:RECOVERY Trial|RECOVERY Trial]] was set up in March 2020, in the UK to test possible treatments for COVID-19. It is run by the Nuffield Departments of Public Health and of Medicine at the [[Organization:University of Oxford|University of Oxford]] and is testing five repurposed drugs and also [[Biology:Antiserum|convalescent plasma]]. The trial enrolled more than 11,500 COVID-19 positive participants in the U.K by June 2020.<ref name="rec-nobenefit" /><ref name="recovery" /><ref>{{cite web|last=Walsh|first=Fergus|date=20 June 2020|title=At last some good news about coronavirus|url=https://www.bbc.co.uk/news/health-53096736|access-date=20 June 2020|website=BBC News|archive-date=31 October 2020|archive-url=https://web.archive.org/web/20201031235147/https://www.bbc.co.uk/news/health-53096736|url-status=live}}</ref>

During April, the British RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was launched initially in 132 hospitals across the UK,<ref name="recov4-3">{{cite web|date=3 April 2020|title=RECOVERY trial rolled out across the UK|url=https://www.recoverytrial.net/news/update|access-date=18 April 2020|publisher=Nuffield Department of Population Health|archive-date=12 October 2020|archive-url=https://web.archive.org/web/20201012030013/https://www.recoverytrial.net/news/update|url-status=live}}</ref> expanding to become one of the world's largest COVID-19 clinical studies, involving 5400 infected people under treatment at 165 UK hospitals, as of mid-April.<ref name="boseley">{{cite news|date=17 April 2020|title=Coronavirus: world's biggest trial of drug to treat Covid-19 begins in UK|language=en-GB|work={{wipe|The Guardian}}|url=https://www.theguardian.com/world/2020/apr/17/world-biggest-drug-trial-covid-19-uk|access-date=18 April 2020|issn=0261-3077|vauthors=Boseley S|archive-date=9 October 2020|archive-url=https://web.archive.org/web/20201009130113/https://www.theguardian.com/world/2020/apr/17/world-biggest-drug-trial-covid-19-uk|url-status=live}}</ref> The trial is examining different potential therapies for severe COVID-19 infection: lopinavir/ritonavir, low-dose [[Biology:Dexamethasone|dexamethasone]] (an anti-inflammatory [[Biology:Steroid|steroid]]), hydroxychloroquine, and [[Chemistry:Azithromycin|azithromycin]] (a common [[Chemistry:Antibiotic|antibiotic]]).<ref name="recovery">{{cite web|date=3 April 2020|title=RECOVERY Trial|url=https://www.recoverytrial.net/|access-date=18 April 2020|publisher=Nuffield Department of Population Health|archive-date=12 October 2020|archive-url=https://web.archive.org/web/20201012051340/https://www.recoverytrial.net/|url-status=live}}</ref> In June, the trial arm using hydroxychloroquine was discontinued when analyses showed it provided no benefit.<ref name="rec-nobenefit" />

On 16 June the trial group released a statement that dexamethasone had been shown to reduce mortality in patients receiving respiratory support.<ref name="RecoveryPress200616">{{cite web|date=16 June 2020|title=Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19|url=https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf|access-date=21 June 2020|archive-date=10 August 2020|archive-url=https://web.archive.org/web/20200810222310/https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf|url-status=live}}</ref> In a [[Placebo-controlled study|controlled trial]] around 2,000 hospital patients were given dexamethasone and were compared with more than 4,000 who did not receive the drug. For patients on ventilators, it cut the risk of death from 40% to 28% (1 in 8). For patients needing oxygen, it cut the risk of death from 25% to 20% (1 in 5).<ref>{{cite news|date=16 June 2020|title=Coronavirus: Dexamethasone proves first life-saving drug|publisher=BBC News Online|url=https://www.bbc.com/news/health-53061281|vauthors=Roberts M|access-date=21 June 2020|archive-date=12 October 2020|archive-url=https://web.archive.org/web/20201012034653/https://www.bbc.com/news/health-53061281|url-status=live}}</ref>

By the end of June 2020, the trial had published findings regarding [[Chemistry:Hydroxychloroquine|hydroxychloroquine]] and [[Biology:Dexamethasone|dexamethasone]].<ref name="rec-nobenefit" /><ref name="oxford news">{{cite news|date=16 June 2020|title=Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19|website=University of Oxford|url=http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications|access-date=16 June 2020|archive-date=16 June 2020|archive-url=https://web.archive.org/web/20200616145052/http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications/|url-status=live}}</ref> It had also announced results for lopinavir/ritonavir which were published in October 2020. The lopinavir-ritonavir and hydroxychloroquine arms were closed to new entrants after being shown to be ineffective.<ref name="rec-nobenefit" /><ref name="lop-rit">{{cite web|date=29 June 2020|title=No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY|url=https://www.recoverytrial.net/files/lopinavir-ritonavir-recovery-statement-29062020_final.pdf|access-date=30 June 2020|publisher=RECOVERY Trial: Statement from the Chief Investigators|archive-date=6 October 2020|archive-url=https://web.archive.org/web/20201006214815/https://www.recoverytrial.net/files/lopinavir-ritonavir-recovery-statement-29062020_final.pdf|url-status=live}}</ref><ref name="reclop">{{cite journal|vauthors=Horby PW, Mafham M, Bell JL, Linsell L, Staplin N, Emberson J, Palfreeman A, Raw J, Elmahi E, Prudon B, Green C|date=October 2020|title=Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial|journal=Lancet|volume=396|issue=10259|pages=1345–1352|doi=10.1016/S0140-6736(20)32013-4|pmc=7535623|pmid=33031764|collaboration=RECOVERY Collaborative Group|s2cid=222135901}}</ref> Dexamethasone was closed to new adult entries after positive results and by November 2020, was open to child entries.

=== PANORAMIC trial ===
{{Main article|Medicine:PANORAMIC trial}}

Launched in December 2021, the PANORAMIC trial will test the effectiveness of [[Chemistry:Molnupiravir|molnupiravir]] and nirmatrelvir/ritonavir in preventing hospitalisation and helping faster recovery for people aged over 50 and those at higher risk due to underlying health conditions.<ref name="nihr.ac.uk">{{cite web |title=NIHR funds community COVID-19 antiviral trial |url=https://www.nihr.ac.uk/news/nihr-funds-community-covid-19-antiviral-trial/29048 |access-date=16 March 2022 |website=www.nihr.ac.uk |language=EN |archive-date=16 March 2022 |archive-url=https://web.archive.org/web/20220316093913/https://www.nihr.ac.uk/news/nihr-funds-community-covid-19-antiviral-trial/29048 |url-status=live }}</ref><ref>{{cite news |date=25 January 2022 |title=Thousands needed to try a new Covid antiviral treatment |language=en-GB |work=BBC News |url=https://www.bbc.com/news/health-60117313 |access-date=16 March 2022 |archive-date=16 March 2022 |archive-url=https://web.archive.org/web/20220316093906/https://www.bbc.com/news/health-60117313 |url-status=live }}</ref> PANORAMIC is sponsored by the [[Organization:University of Oxford|University of Oxford]] and funded by the National Institute for Health Research (NIHR).<ref name="nihr.ac.uk"/> As of March 2022 has over 16,000 people enrolled as participants making it the largest study into COVID-19 antivirals.<ref>{{cite web |last=Pinching |first=John |date=22 February 2022 |title=PANORAMIC view of World's largest COVID study |url=https://www.pharmatimes.com/news/panoramic_view_of_worlds_largest_covid_study_1388052 |access-date=16 March 2022 |website=PharmaTimes |archive-date=18 March 2022 |archive-url=https://web.archive.org/web/20220318143429/https://www.pharmatimes.com/news/panoramic_view_of_worlds_largest_covid_study_1388052 |url-status=live }}</ref>

== See also ==
* Cost of drug development
* [[Biology:COVID Moonshot|COVID Moonshot]]

{{Clear}}

== References ==
{{reflist}}

== Further reading ==
* {{cite journal |vauthors=Kaplon H, Reichert JM |title=Antibodies to watch in 2021 |journal=mAbs |volume=13 |issue=1 |page=1860476 |date=2021 |pmid=33459118 |pmc=7833761 |doi=10.1080/19420862.2020.1860476 |doi-access=free | title-link=doi }}
* {{cite journal | vauthors = McCreary EK, Pogue JM | title = Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options | journal = Open Forum Infectious Diseases | volume = 7 | issue = 4 | pages = ofaa105 | date = April 2020 | pmid = 32284951 | pmc = 7144823 | doi = 10.1093/ofid/ofaa105 | doi-access = free |title-link=doi }}
* {{cite journal |vauthors=Tuccori M, Ferraro S, Convertino I, Cappello E, Valdiserra G, Blandizzi C, Maggi F, Focosi D |title=Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline |journal=mAbs |volume=12 |issue=1 |page=1854149 |date=2020 |pmid=33319649 |pmc=7755170 |doi=10.1080/19420862.2020.1854149 |doi-access=free |title-link=doi }}
* {{cite journal |vauthors=Yang L, Liu W, Yu X, Wu M, Reichert JM, Ho M |title=COVID-19 antibody therapeutics tracker: a global online database of antibody therapeutics for the prevention and treatment of COVID-19 |journal=Antib Ther |volume=3 |issue=3 |pages=205–12 |date=July 2020 |pmid=33215063 |pmc=7454247 |doi=10.1093/abt/tbaa020 |doi-access=free |title-link=doi }}

== External links ==
* [https://www.who.int/teams/blueprint/covid-19 R&D Blueprint and COVID-19], [[Organization:World Health Organization|World Health Organization]]
* [https://www.niaid.nih.gov/diseases-conditions/coronaviruses Coronaviruses by US National Institute for Allergy and Infectious Diseases]
* [https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-therapeutics-tracker COVID-19 therapeutics tracker] Regulatory Affairs Professionals Society
* {{cite web | title=COVID-19 treatments: research and development | date=18 February 2021 | publisher=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/treatments-covid-19/covid-19-treatments-research-development | access-date=16 June 2021 | archive-date=23 October 2021 | archive-url=https://web.archive.org/web/20211023025735/https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/treatments-covid-19/covid-19-treatments-research-development }}

{{Monoclonals for infectious disease and toxins}}

[[Category:Clinical research]]
[[Category:Vaccines]]

{{Sourceattribution|COVID-19 drug development}}