- Researchers have been studying antiviral medications like remdesivir and hydroxychloroquine in the hopes that they will be effective treatments against COVID-19.
- A new study, however, indicates that these drugs provide no benefit in treating this disease.
- Several other types of treatments — such as monoclonal antibodies, convalescent plasma, and various immune modulators — are also being studied.
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One of the avenues being explored by researchers in the battle against COVID-19 is the repurposing of existing medications.
Developing new drugs is a costly and time-consuming process that can take billions of dollars and several years to complete — if the drug is safe and effective enough to cross the finish line in the first place.
Finding new ways to use medications that we already have, according to Dr. Sanjay Sethi, a researcher at the University at Buffalo, has many advantages.
Scientists already know a great deal about these drugs in terms of their activity, adverse effects, and dosing, Sethi explained.
This allows researchers to bypass phase 1 research and proceed directly to phase 2 or phase 3 studies, substantially reducing the time needed to develop a new drug.
This is what is currently happening with antivirals like remdesivir and hydroxychloroquine.
However, a new study indicates that these medications may not be as effective as we had hoped.
The World Health Organization (WHO) conducted a large, randomized trial to evaluate the efficacy of four antiviral medications: remdesivir, hydroxychloroquine, lopinavir, and interferon.
These medications are currently being used to treat patients who have been hospitalized with COVID-19.
The study included 11,266 COVID-19 patients who were admitted to 405 hospitals in 30 countries.
These patients were randomly divided into different groups, depending upon the medication that was administered.
- 2,750 of them received remdesivir
- 954 received hydroxychloroquine
- 1,411 received lopinavir
- 651 received interferon and lopinavir
- 1,412 received interferon
- 4,088 did not receive any drug.
There were no placebos.
The researchers’ main goal was to assess in-hospital mortality, but they also examined duration of hospital stay and initiation of ventilation.
The trial found that none of the drugs studied provided any benefit for the patients in any of the areas that were assessed.
According to Dr. Thad Stappenbeck, chair of the department of inflammation and immunity at Cleveland Clinic’s Lerner Research Institute, four repurposed antiviral drugs — remdesivir, hydroxycholoroquine, lopinavir, and interferon beta-1a — had previously been tested in smaller, non-randomized trials.
In the preliminary studies, it appeared that these drugs might have some benefit for treating COVID-19.
However, this current trial, which was a large, randomized trial including thousands of patients, failed to confirm these early hopes.
None of the drugs had any demonstrable effect on any of the outcome measures, including death, use of mechanical ventilation, or duration of hospital stay, said Stappenbeck.
“The current study in the NEJM is important as it follows the best practices of trial design,” said Stappenbeck, “which allows it to make firm conclusions.”
He added, “In short, none of these drugs are effective in patients that are ill with COVID-19 and need hospitalization.”
Stappenbeck noted that dexamethasone still has benefit in treating COVID-19 patients and is commonly used in hospitals.
It is not recommended for milder cases.
Their panel of experts bases this recommendation on “moderate certainty” evidence that its administration can reduce mortality in more severe cases.
Other promising treatments, according to Stappenbeck, are engineered anti-SARS-CoV-2 monoclonal antibodies, convalescent plasma, and immune modulators.
These treatments are currently undergoing phase 3 trials.
Stappenbeck said that the Eli Lilly drug bamlanivimab and the Regeneron cocktail of casirivimab and imdevimab have emergency use authorization in patients that have not yet progressed to severe disease.
It provides the recipient with the benefit of the antibodies that the donor developed during their illness.
Immune modulators are drugs that “activate, boost, or restore normal immune function.”
Dexamethasone is one such drug, but there are several others.
The hope with using immune modulators is that they will quell the “cytokine storm” that develops in some COVID-19 patients.
It can lead to dangerous complications, such as acute respiratory distress syndrome and multiple organ failure.
Repurposing existing drugs is one way that scientists can speed up the development of new treatments.
Certain antiviral medications, like remdesivir and hydroxychloroquine, appeared to be promising COVID-19 treatments in early trials.
However, a larger, better-quality study has found they seem to have no measurable benefit.
Research continues though with several other promising treatments — including monoclonal antibodies, convalescent plasma, and immune modulators.