As COVID-19 sweeps across the country and over one million people in the U.S. have been diagnosed with the virus, researchers have been anxiously trying to find a treatment. In April 2020, news broke that the clinical trials for Remdesivir have shown modest benefits against the virus. Remdesivir is a nucleotide analog, meaning it prevents the replication of the virus in the body. This means that it inhibits viral RNA polymerase from operating.
Amino acids make proteins through two processes: translation and transcription. Amino acids are used by living organisms to make proteins, which serve many functions to keep us alive. The type of proteins made depends on the sequence of an amino acid chain. About 1/5 of our body is made out of proteins and all cellular components in our body use proteins to execute functions. The two major steps in making a protein include transcription and translation.
During transcription, a cell makes a copy of its DNA, called RNA. The difference between RNA and DNA is that DNA contains the sugar deoxyribose, while RNA contains the sugar ribose. Translation is the process of converting RNA into a sequence of amino acids, which makes up the protein.
In both transcription and translation, different molecules are responsible for adding and removing nucleotides. The key factor for the conversion of DNA to RNA during transcription is a molecule called RNA polymerase. As noted earlier, Remdesivir inhibits this viral RNA polymerase, so that no RNA can be made. SARS-CoV-2 is made from RNA, so as a summary, Remdesivir prevents the virus from being created.
In early April, The New England Journal of Medicine released a study on the use of Remdesivir in fifty-three patients with severe clinical manifestation of COVID-19. Patients involved in the study were from many different countries, including the United States, Japan, Italy, Austria, France, Germany, Neverlands, Spain, and Canada. Fourteen of the participants were men and thirteen were women. Many of the patients were over 60 years old and had pre-existing health conditions. The results showed that 68% of the individuals improved while 15% did worse. Out of the 8 participants that experienced a decline in health, 7 of them died. Thirty-two patients (60%) reported adverse events during the trial. These side effects include things like: diarrhea, rash, kidney injuries, and failure renal impairment, low blood pressure, acute kidney injury, and septic shock. Also, four of the patients had to stop using Remdesivir due to how intensively the drug was developing multi-organ failures. The research stressed that the patients who were chosen for this study were severely ill and had a high mortality rate, including 64% being on invasive ventilation. Also, many of the patients chosen were males over the age of sixty and had coexisting conditions.
Gilead Sciences, an American biopharmaceutical company that researches, develops, and commercializes drugs and performed their own study, also came out with a report. Gilead suggests that patients are responding positively to the treatment. The study looked at 125 patients at the University of Chicago; 113 of the individuals were in critical condition. The data showed that two individuals died after being given Rremdesivir, and most patients were discharged from the hospital after only six days, significantly lower than the average ten days.
In a “normal” scenario, once a drug is believed to improve the care of patients during preclinical research, it goes through 5 clinical trials, also known as phases.
● In Phase 0, researchers try to collect data on how the drug affects a test group of around ten people.
● If the data is positive, then Phase I occurs. Health administrators will try to determine the safest dosage for a patient. This phase of the trial also only includes a small group of people. Each patient is given a low dose to start, and then the dose is increased until one of two things happen: The desired results are demonstrated or the side effects are too severe.
● Phase II: More patients enter the trial. This phase aims to further examine the safety and efficiency of the drug.
● Next, in Phase III: The drug being researched is compared to the standard-of-care drug using two groups. One group is given the new drug and the second group is given the current standard-of-care currently being used in the market. In order to decrease confounding variables, these trials are randomized, meaning that the groups are randomly assigned, usually by a computer program. Doctors and researchers are not told which patients are being treated with which drug, to decrease bias.
● Lastly, in Phase IV, the FDA approves the new drug. There are strict guidelines for a drug to be approved. For example, a large sample size is needed to prove that the drug is both safe and effective.
The drug trial for Rremdesivir has recently finished Phase III, evaluating efficacy and safety. Currently, 6 studies are being done on the drug. Beginning in March 2020, approximately one thousand individuals were tested with the drug, but mainly in countries with the highest prevalence of the pandemic. In China, researchers are conducting a study to compare how hospitalized patients with and without supplemental oxygen are responding to the drug. The 2 studies examine how patients are responding to the drug based on the severity of their illnesses. For example, patients hospitalized that need supplemental oxygen versus patients who are hospitalized and do not need supplemental oxygen. Besides China, the National Institute of Allergy and Infectious Diseases (NIAID) in the United States and the National Institute for Health and Medical Research (INSERM) in France are in the midst of conducting their own research on Rremdesivir.
The reporting of Remdesivir has given many a sense of optimism. While Gilead has not shared their data yet, many medical professionals are not able to assess the drug’s risks and benefits. The studies that Gilead has released are uncontrolled studies; patients taking Remdesivir were not compared to patients not taking Remdesivir or people who are either taking a different treatment or no treatment.
Bottom line upfront:
● The studies of Remdesivir with optimistic results were not completed under Food and Drug Administration testing protocols
● Data has not been provided to medical professionals so they are unable to assess risks and benefits of Remdesivir as a treatment for COVID-19
● Further study, including clinical trials as detailed in this paper, need to occur before medical professionals can say Remdesivir is a treatment for COVID-19
Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. New England Journal of Medicine. October 2020. DOI:10.1056/nejmoa2007016.
Kolata G. Gilead Claims ‘Positive Data’ to Come From N.I.H. Trial of Remdesivir. The New York Times. https://www.nytimes.com/2020/04/29/health/gilead-remdesivir-coronavirus.html. Published April 29, 2020. Accessed April 30, 2020.
National Comprehensive Cancer Network. Phases of clinical trials. https://www.nccn.org/patients/resources/clinical_trials/phases.aspx. Accessed April 30, 2020.
Remdesivir Clinical Trials. Gilead Creating Possible. https://www.gilead.com/purpose/advancing-global-health/covid-19/remdesivir-clinical-trials. Accessed April 30, 2020.