Clinical trials of chloroquine and its less toxic metabolite, hydroxychloroquine, are ongoing or due to start in other countries. Both drugs have been shown to be effective against the new coronavirus in in-vitro laboratory studies Results from initial clinical trials suggest both drugs may be effective against COVID-19.
The US Food & Drug Administration (FDA) has confirmed it plans to conduct a large clinical trial to investigate chloroquine (Resochin) for the treatment of COVID-19, the disease caused by the new coronavirus (SARS-CoV-2). Stephen Hahn, the FDA Commissioner, stated that the FDA would be looking into whether the drug, which has been on the market for more than 70 years, would be of benefit to people with COVID-19. Clinical trials are being rolled out after US President Trump’s March 19, 2020, announcement that the drug would be made available in the US.
What are chloroquine and hydroxychloroquine?
Chloroquine is an antimalarial and amebicidal drug that is already approved in the US. A hydroxylated version of the drug, hydroxychloroquine, is also available and is primarily used to treat rheumatoid arthritis, systemic lupus erythematosus, and discoid lupus erythematosus.
Hydroxychloroquine is less toxic than chloroquine.
Why are these drugs being investigated?
Chloroquine was already known to be effective at preventing the spread of the SARS coronavirus in cell cultures. This discovery was made following the 2003 SARS epidemic. The drug blocks the coronavirus from getting into cells and has additional immuno-modulating activity, which may increase its effectiveness. In light of these findings, researchers rushed to investigate the potential of chloroquine and hydroxychloroquine in in-vitro studies when the new coronavirus broke out. The laboratory studies confirmed that both drugs were highly effective at controlling the spread of the new virus, which led researchers to test the drugs in actual patients with COVID-19.
One of the benefits of testing older drugs with a proven track record is that their safety profile is well known. Another is that they are available at low cost.
What to know about the current use of the drugs for COVID-19?
Chloroquine is included in the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition) guidelines. It has also been included in the treatment guidelines of other countries, such as South Korea and Belgium. Clinical trials of chloroquine began in COVID-19 patients in China earlier this year.
Initial results showed that patients taking chloroquine demonstrated improvements across a range of indicators compared with those who did not receive the drug. Researchers observed that patients taking chloroquine showed improvements in their CT lung images, had their fevers reduce more quickly and they tested negative for the virus sooner. Their recovery was also quicker.
Positive results have also been reported from a small French study, which showed hydroxychloroquine was effective in reducing the viral load in patients with COVID-19. The addition of the antibacterial agent azithromycin to the regimen was also found to be beneficial.
In addition to the clinical trials that will be conducted in the US, the World Health Organization (WHO) also recently announced that it will be conducting clinical trials of chloroquine and hydroxychloroquine for COVID-19. The trials will be conducted in a number of countries.
How long will it take for the drugs to be available for clinical trials?
Bayer (chloroquine, Resochin) and Sanofi (hydroxychloroquine, Plaquenil) have both announced plans to make millions of doses of their branded versions of the drugs available. Novartis and others who manufacture generic versions of the drugs are also preparing to increase supplies of the drugs.
CNBC. Trump directs FDA to examine whether malaria drugs can be used for coronavirus. March 29, 2020. [Accessed March 21, 2020]. Available at: https://www.cnbc.com/2020/03/19/coronavirus-treatment-trump-directs-fda-to-examine-whether-malaria-drug-can-be-used.html.
The Wall Street Journal. U.S. Moves to Expand Array of Drug Therapies Deployed Against Coronavirus. March 19, 2020. [Accessed March 21, 2020]. Available at: https://www.wsj.com/articles/trump-expected-to-detail-new-virus-therapies-but-expansion-could-be-controversial-11584629965.
Vincent MJ, Bergeron E, Benjannet S et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. August 22, 2005. Virol J. 2005; 2: 69. DOI: 10.1186/1743-422X-2-69.
Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). March 9 2020 (online ahead of print). Clin Infect Dis. DOI: 10.1093/cid/ciaa237.
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269–271 (2020). https://doi.org/10.1038/s41422-020-0282-0.
Reuters. Bayer donates three million malaria tablets to U.S. for potential use against coronavirus. March 20, 2020. [Accessed March 21, 2020]. Available at: https://www.reuters.com/article/us-health-coronavirus-bayer/bayer-donates-three-million-malaria-tablets-to-us-for-potential-use-against-coronavirus-idUSKBN21637E.
ChiCTR. Chinese Clinical Trial Registry. Chloroquine + COVID-19 trial search results. [Accessed March 21, 2020]. Available at: http://www.chictr.org.cn/searchprojen.aspx?title=Chloroquine&officialname=&subjectid=&secondaryid=&applier=&studyleader=ðicalcommitteesanction=&sponsor=&studyailment=COVID-19&studyailmentcode=&studytype=0&studystage=0&studydesign=0&minstudyexecutetime=&maxstudyexecutetime=&recruitmentstatus=0&gender=0&agreetosign=&secsponsor=®no=®status=0&country=&province=&city=&institution=&institutionlevel=&measure=&intercode=&sourceofspends=&createyear=0&isuploadrf=&whetherpublic=&btngo=btn&verifycode=&page=1.
COVID-19-CSC. Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition). March 4, 2020. [Accessed March 21, 2020]. Available at: http://kjfy.meetingchina.org/msite/news/show/cn/3337.html.
STAT. WHO to launch a multinational trial to jumpstart the search for coronavirus drugs. March 18, 2020. [Accessed March 21, 2020]. Available at: https://www.statnews.com/2020/03/18/who-to-launch-multinational-trial-to-jumpstart-search-for-coronavirus-drugs/.
Business Insider. Could a malaria pill from the 1940s treat the coronavirus? Early results for chloroquine have caught the eyes of doctors, analysts – and even Elon Musk. March 18, 2020. [Accessed March 21, 2020]. Available at: https://www.businessinsider.in/science/news/could-a-malaria-pill-from-the-1940s-treat-the-coronavirus-early-results-for-chloroquine-have-caught-the-eyes-of-doctors-analysts-and-even-elon-musk/articleshow/74698558.cms.
The New York Times. With Minimal Evidence, Trump Asks F.D.A. to Study Malaria Drugs for Coronavirus. March 19, 2020. [Accessed March 21, 2020]. Available at: https://www.nytimes.com/2020/03/19/health/coronavirus-drugs-chloroquine.html.
EN24. Hydroxychloroquine would be effective, according to Professor Raoult of the IHU in Marseille, after a first limited test. March 17, 2020. [Accessed March 21, 2020]. Available at: https://www.en24.news/a/2020/03/hydroxychloroquine-would-be-effective-according-to-professor-raoult-of-the-ihu-in-marseille-after-a-first-limited-test.html.
Fierce Pharma. Novartis, Mylan, and Teva to supply tens of millions of chloroquine tablets to fight COVID-19. March 20, 2020. [Accessed March 21. 2020]. Available at: https://www.fiercepharma.com/pharma/new-commitments-mylan-and-teva-move-to-supply-tens-millions-hydroxychloroquine-tablets-to.
AA News. France: Sanofi offers a potential drug to beat COVID-19. March 18, 2020. [Accessed March 21, 2020]. Available at: https://www.aa.com.tr/en/europe/france-sanofi-offers-potential-drug-to-beat-covid-19/1770571.
Posted: March 2020