Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity. Remdesivir’s mechanism of action is an adenosine nucleotide analogue that disrupts RNA polymerase function, resulting in decreased viral RNA production. The drug is being developed by Gilead Sciences, a major player in the biopharmaceutical space, but for anyone not familiar with Gilead, it is most notably famous for its blockbuster drugs in the treatment of HIV, hepatitis B, hepatitis C and influenza. Why are we talking about this drug? Let us take a step back.
If you have watched the news in the last two months, you will have heard about COVID-19 and most likely about the solution of a vaccine. Dr. Anthony Fauci, President Donald Trump, Dr. Deborah Birx, and many others have suggested the solution to normalcy in this pandemic is a vaccine. But wait, doesn’t it take 10+ years to develop a vaccine? Every vaccine is different, but research suggests that 10-15 years is the average range from soup to nuts. In 1967, the mumps vaccine was developed in four years, which is considered the fastest ever approved (1).
That was over 40 years ago, we can beat that! This is the mantra of many optimists today (and we hope they are right). However, the Federal Drug Administration (FDA) approval process is a very rigorous and stringent journey. Many beg the question, can we loosen the rules on the guidelines? There is the FDA fast track, designed to expedite the delivery of drugs to the market. We must walk the line with this process though, the three phases were put in place for a reason. For example, during the SARS outbreak, some preliminary vaccines enhanced the disease in model experiments. Below is a timeline of the drug approval process (2).
You may be thinking “great, so you are telling me I need to quarantine for 15 years?” No, we are not. The aforementioned drug, remdesivir, may be the answer. Back in 2013, Gilead began researching and developing remdesivir to combat the Ebola outbreak in West Africa. Two other drugs proved to be more effective, which caused Gilead to put their pencils down on remdesivir. Gilead has also researched the efficacy of the drug against MERS and SARS. Remdesivir has demonstrated in vitro and in vivo activity in animal models against MERS and SARS – both of which are coronaviruses and structurally similar to COVID-19.
On May 2, the FDA granted remdesivir an Emergency Use Approval. The emergency use authorization allows for the drug to be distributed in the U.S. and administered to patients intravenously by healthcare providers to treat COVID-19 in adults and children hospitalized with severe disease. Severe disease is defined as patients with low blood oxygen levels or needing oxygen therapy such as a mechanical ventilator (3). Other times the Emergency Use Approval was exercised in extreme situations include H7N9 Influenza in 2013, Ebola in 2014, Enterovirus D68 in 2015 and Zika Virus (4).
The emergency authorization has seen reactions from both ends of the spectrum: cheers of hope and severe criticism. Most criticism is being drawn from individuals who view the expedited process as an unfair advantage for large biopharmaceutical companies to profit from this pandemic. It is argued that these companies utilize taxpayer dollars in the form of government grants for drug research and development, which in turn creates a product the company can sell for a profit.
The other side of the argument would be that we do not have any other options and who better to develop these drugs then large, well-capitalized pharmaceutical companies. Although businesses utilize government grants, they also invest with shareholder dollars for R&D. In order to develop a drug, the company takes on a massive risk with the investment of capital and manpower. To put matters into perspective, Gilead was granted a $37.5 million grant from the U.S. government, but is estimated to spend approximately $1 billion on the remdesivir program (5). Gilead has announced it will donate 1.5 million doses of remdesivir or enough to treat 140,000 patients at zero cost to the patient (5). Experts do not believe remdesivir will be a major revenue generator for Gilead and the drug is reserved for patients with no other options in critical condition. We will leave it up to you folks on where you fall on the issue.
We trend towards favoring optimism, but we would like to make a note of realism. There are several viral diseases without a vaccine and flu vaccines in particular often fail in the elderly (the most vulnerable population to COVID-19). The world must accept the fact that a successful vaccine may never be developed for COVID-19 or it may take years.
It is unknown yet the large-scale efficacy of remdesivir as well as the side effects, but healthcare providers remain hopeful. It will be interesting to see the success rate of drugs developed to combat COVID-19 as they roll out. Want to hear more COVID-19 updates in future blogs? Comment below topics you would like covered.