By the bioMérieux Connection Editors
As cases of COVID-19 are on the rise again in several places in the U.S., the need for effective treatment remains. Many potential COVID-19 treatments that could have an impact on our ability to fight the virus are currently being developed or tested in clinical trials. Several companies are working on antiviral drugs to treat the disease. Other companies are working on treatments that may control the immune system’s dysregulated response to the virus, or treatments that use antibodies and/or plasma. As of July 6, 2020, two medications have received emergency use authorization (EUA) from the Food and Drug Administration (FDA) to help treat COVID-19. One is the antiviral, remdesivir, and the other is a drug used to sedate people on ventilators, Fresenius Propoven 2%.
Using Drugs That Already Exist to Treat COVID-19
Sometimes it can take a decade or more for a new treatment to go from initial discovery to the marketplace. That’s why many medications being considered as potential treatments for COVID-19 are drugs that already exist and why Emergency Use Authorization (EUA) is available to support the development pathway. EUA authority allows the FDA to help strengthen the nation’s public health response by facilitating the availability of medical countermeasures (MCMs) needed during public health emergencies. It waives the formal FDA approval process for MCMs and replaces it with a different, less stringent process, but only for a set amount of time.For example, Fresenius Propoven 2% is a double concentration of the widely used drug propofol. It was granted EUA because of the increased demand for propofol to sedate COVID-19 patients on ventilators worldwide. The EUA will end when the COVID-19 declaration justifying emergency use of authorized products is terminated, or revoked, or when there is a change in the approval status of the product.
Using Antivirals to Treat COVID-19
EUA for Remdesivir
Remdesivir was developed by Gliead Sciences about a decade ago and was initially created as a general antiviral candidate. In the past, it was tested on volunteers with a number of different viruses, including Ebola and Middle East Respiratory Syndrome (MERS). Although it was not successful in treating Ebola, research showed the drug’s potential to block the replication of MERS-CoV. MERS-CoV is the coronavirus that causes MERS and it is related to SARS-CoV-2—the coronavirus that causes COVID-19.
In early March, at the initial peak of the COVID-19 outbreak in many parts of the world, remdesivir began to be tested in clinical trials to determine its effect on COVID-19 patients. It was identified early as a potential treatment because of its known activity against MERS. Many of the COVID-19 remdesivir trials were set to be completed very quickly and provide results within a couple months. Overall, clinical trial results were mixed, with some showing that the drug provided no benefit to COVID-19 patients. However, one study demonstrated that patients in a 5-day remdesivir treatment group were 65% more likely to have clinical improvement at Day 11 compared with those in a standard care group. On May 1, 2020, remdesivir was granted EUA to treat certain hospitalized COVID-19 patients because of this early data. Currently, a large number of studies are in progress to determine if remdesivir is truly a safe and effective COVID-19 treatment.
Other COVID-19 Antiviral Drugs in the Pipeline
Currently, a clinical trial is being conducted by the National Institutes of Health to determine whether remdesivir paired with baricitinib may be effective in treating COVID-19. Baricitinib is a janus kinase (JAK) inhibitor approved as a treatment for adults with moderately to severely active rheumatoid arthritis, used in the U.S. and in more than 65 additional countries. The trial is the next iteration of the National Institute of Allergy and Infectious Diseases’ Adaptive COVID-19 Treatment Trial, which began at the end of February 2020 to evaluate remdesivir.
Many of the other drugs being developed or tested for COVID-19 are also antivirals. EIDD-2801 is an antiviral that is being studied in clinical trials in the U.K. and U.S. Unlike remdesivir, EIDD-2801 can be taken orally, which would make it available to a larger number of people if the drug proves to be safe and effective. Additional antiviral drugs that are being tested in clinical trials include favipiravir, lopinavir/ritonavir, and merimepodib with remdesivir.
Using Immune System Modulators to Treat COVID-19
When some people acquire COVID-19, their immune system goes into overdrive, releasing large amounts of signaling proteins called cytokines. Some researchers believe this “cytokine storm” may be the reason certain people with severe COVID-19 develop acute respiratory distress syndrome (ARDS) and need to be put on a ventilator. Many immune suppressants are being tested in clinical trials to see whether the drugs can subdue the cytokine storm, such as CM4620-IE and IL-6 inhibitors. The FDA has also authorized a blood purification device that can reduce the amount of cytokines in the bloodstream.
The steroid dexamethasone has recently been shown to reduce deaths of COVID-19 patients on ventilators by one third. Although it does not affect patients with less severe cases of COVID-19, the inexpensive and commonly used drug could save the lives of those who are seriously ill. The use of steroids to treat viral respiratory infections is controversial, but dexamethasone could treat COVID-19 by suppressing the immune system and treating ARDS. A widespread, rigorous clinical trial will be needed to determine how safe and effective dexamethasone can be.
Using Antibodies to Treat COVID-19
Certain antibodies can trigger the immune system to attack SARS-CoV-2. Antibodies can be laboratory-made or come from the plasma of those who have recovered from COVID-19. On May 1, 2020, the FDA released guidance on pathways for use of investigational COVID-19 convalescent plasma from recovered patients. Because COVID-19 convalescent plasma has not yet been approved for use by the FDA, it is regulated as an investigational product.
Laboratory-made antibody drugs to treat COVID-19 are also in the process of being developed. The biotech company Sorrento Therapeutics announced in mid-May the development of an antibody drug that was effective in blocking SARS-CoV-2 in early testing. Other companies such as AbCellara, and Regereron Pharmaceuticals Inc. have acquired isolated antibodies from people who have recovered from the disease and are working on testing them to potentially create an antibody treatment.
Developing an Effective Treatment for COVID-19
Just like vaccines, there are a large number of potential treatments being developed and tested to see if they can safely and effectively improve outcomes for COVID-19 patients. Both the National Institute of Health and the Infectious Disease Society of America have published recommendations on the treatment and management of patients with COVID-19, which are routinely updated as new information becomes available. Although it may be months or possibly years before we have definitively proven, effective treatment options, scientists are learning about the virus, its effects, and treatment to continuously improve our ability to combat the it.
Opinions in this article are not necessarily those of bioMérieux, Inc.
