Drug repositioning (also called drug repurposing) – the investigation of existing drugs for new therapeutic purposes – is one line of scientific research which is followed to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine.
In a statement to the journal Nature Biotechnology in February 2020, US National Institutes of Health Viral Ecology Unit chief Vincent Munster said, "The general genomic layout and the general replication kinetics and the biology of the MERS, SARS and [SARS-CoV-2] viruses are very similar, so testing drugs which target relatively generic parts of these coronaviruses is a logical step".
Drug repositioning (also known as drug repurposing, re-profiling, re-tasking or therapeutic switching) is the repurposing of an approved drug for the treatment of another disease or medical condition.
Chloroquine is an anti-malarial medication that is also used against some auto-immune diseases. On 18 March, the WHO announced that chloroquine and the related hydroxychloroquine would be among the four drugs studied as part of the Solidarity clinical trial. New York governor Andrew Cuomo announced that New York State trials of chloroquine and hydroxychloroquine would begin on 24 March.NYU Langone Medical School is conducting a trial on the safety and efficacy of preventative use of hydroxychloroquine.
Preliminary results had found that chloroquine may be effective and safe in treating COVID-19 associated pneumonia. The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of patient's hospital stay" and recommended it for people diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia. Two studies in France and China found benefits of treatment with hydroxychloroquine and azithromycin for cases where illness was not yet severe, but a small study in France of 11 patients did not find any evidence that the combination was effective in patients with severe COVID-19 infection. One small trial from China found chloroquine may be slightly better than lopinavir/ritonavir.
Preliminary clinical trials to evaluate the safety and efficacy of hydroxychloroquine for treating COVID-19 infection are planned in the United States, but the CDC stated that "the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection" were not yet established. On March 28, 2020 the FDA authorized the use of hydroxychloroquine sulfate and chloroquine phosphate under an Emergency Use Authorization (EUA). The treatment has not been approved by the FDA. The experimental treatment is authorized only for emergency use for patients who are hospitalized but are not able to receive treatment in a clinical trial.
Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir was "clearly effective". Of 35 patients in Shenzhen tested negative in a median of 4 days, while the length of illness was 11 days in the 45 patients who did not receive it. In a study conducted in Wuhan on 240 patients with pneumonia half were given favipiravir and half received umifenovir. The researchers found that patients recovered from coughs and fevers faster when treated with favipiravir, but that there was no change in how many patients in each group progressed to more advanced stages of illness that required treatment with a ventilator.
On 22 March 2020, Italy approved the drug for experimental use against COVID-19 and began conducting trials in the three regions most affected by the disease. The Italian Pharmaceutical Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.
The drug may be less effective in severe cases of illness where the virus has already multiplied. It may not be safe for use by pregnant women or those trying to conceive. According to the South China Morning Post, Shinzo Abe has made overtures to the Trump administration about the drug.
On 2 April 2020, Germany announced that it will purchase large stockpiles of the drug from Japan, then use the German military to deliver the drug to German university hospitals, where the drug will be used to treat German COVID-19 patients.
UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.
There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS, since it is unlikely that a drug developed specifically against HIV will work for a very different virus (it is more likely that general-purpose antivirals will work). The WHO included lopinavir/ritonavir in the international Solidarity trial.
One issue with antiviral treatment is the development of resistance through mutations that can lead to more severe disease and transmission. Some early pretrial studies suggest that Remdesivir may have a high genetic barrier to resistance. Data from clinical trials is expected in April 2020.
There are three ongoing clinical trials of intravenous vitamin C for people who are hospitalized and severely ill with COVID-19; two placebo controlled (China, Canada) and one with no control (Italy).
Japan's National Center for Global Health and Medicine (NCGM) is planning a clinical trial for Teijin's Alvesco (ciclesonide), an inhaled corticosteroid for asthma, for the treatment of pre-symptomatic patients infected with the novel coronavirus.
A form of angiotensin-converting enzyme 2, a Phase II trial is underway with 200 patients to be recruited from severe, hospitalized cases in Denmark, Germany, and Austria to determine the effectiveness of the treatment.
Repurposed drugs by type
Since SARS-CoV-2 is a virus, considerable scientific attention has been focused on repurposing approved anti-viral drugs that were developed for prior outbreaks such as MERS, SARS, and West Nile virus.
^Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia (February 2020). "[Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia] (abstract in English; article in Chinese)". Chinese Journal of Tuberculosis and Respiratory Diseases (in Chinese). 43: E019. doi:10.3760/cma.j.issn.1001-0939.2020.0019. ISSN1001-0939. PMID32075365.
^Molina, Jean Michel; Delaugerre, Constance; Goff, Jerome Le; Mela-Lima, Breno; Ponscarme, Diane; Goldwirt, Lauriane; De Castro, Nathalie (2020). "No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection". Médecine et Maladies Infectieuses. doi:10.1016/j.medmal.2020.03.006. PMID32240719.
^Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang (18 March 2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. doi:10.1056/NEJMoa2001282. ISSN0028-4793. PMID32187464.
^"Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease". doi:10.1128/mBio.00221-18. Cite journal requires |journal= (help)