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Merck (MSD) and Ridgeback Biotherapeutics recently announced that it is seeking approval from the FDA for what would be the first antiviral pill to treat COVID-19. The drug, molnupiravir, reduced the risk of hospitalization and death of COVID-19 by nearly 50 percent, according to their Phase 3 study. Health Canada says it collaborates with international counterparts to review the Merck-developed experimental pill, as a CTV News article mentioned.
What is Molnupiravir, and How Does it Work?
According to a Medical News Today article, molnupiravir is in a class of antivirals known as mutagenic ribonucleosides, which alter the viral genetic material and induce errors, preventing viral genome replication and transcription. Molnupiravir is turned into triphosphate within the host cell so that when the virus attempts to replicate, it replaces the nucleoside cytidine in the viral RNA to cause a mutation.
Dr. Albert Shaw, MD, a Yale Medicine infectious diseases specialist, explains in more detail how the drug prevents the SARS-COV-2 virus from replicating when the drug enters your bloodstream. An important structural feature is that molnupiravir similar to the nucleosides required to produce the coronavirus’ RNA, which is why it can incorporate itself into the genetic material during RNA synthesis. Dr. Shaw says, “When this RNA is translated into viral proteins, the virus cannot operate because the proteins have too many mutations.”
According to a Nature article, two Indian drugmakers testing generic molnupiravir in patients with moderate COVID-19 symptoms just paused their trials, citing a lack of substantial evidence of effectiveness. However, they plan on continuing trials for people with mild illnesses. Merck’s findings have been provided in a press release, but have yet to be reviewed by scientists and approved by the FDS, were based on patients with mild-to-moderate COVID-19 cases. As mentioned by a Merck spokesperson, moderate COVID-19 cases in India are more severe than those in the United States and require hospitalization.
Effectiveness
The medication, according to Merck, reduced the chance of hospitalization or death by half. In the Phase 3 trial, 7 percent of volunteers in the drug group were admitted to the hospital, but no casualties took place. Fourteen percent of those who received a placebo were hospitalized or died.
However, the 50 percent effectiveness rate is lower than that of monoclonal antibodies, an intravenous therapy used to treat high-risk patients with mild or moderate COVID-19 symptoms. According to studies, such antibodies cut hospitalizations and mortality among individuals by up to 85%.
The Medical News Today article also mentions that several scientists have expressed concerns over the safety of a drug that works by causing mutations as it might cause mutations in host cells. In a study in animal cell cultures, mutations were discovered in cells treated with molnupiravir. This has raised concerns that the drug may cause cancers or congenital disabilities. Despite that, Professor William Schaffner, a professor of infectious diseases at Vanderbilt University School of Medicine, was less concerned about the potential genetic effects, stating, “the FDA would certainly not have permitted clinical trials in humans if they thought there was any reasonable danger. [...] Animal studies showed no adverse effects.”
Who Will Receive the Pills?
According to a New York Times article, the tablets are for those who are unwell with coronavirus but do not need to be admitted to the hospital. Merck's Phase 3 clinical research only recruited unvaccinated patients who were considered high risk, such as the trial or those who had diabetes or heart problems. The medication may initially be offered solely to those individuals, but experts expect it to become more broadly available in the future.
The pills are intended to be given as soon as possible after a person develops symptoms of COVID-19. This is when the virus is rapidly multiplying, and the immune system has yet to establish resistance. Volunteers in Merck's trial had to have had symptoms within the previous five days, and other researchers believe the pills should be taken even sooner.
How is Merck’s Pill a Game-Changer?
Other drugs that can interfere with the viral RNA, such as remdesiver, an intravenously administered drug. On the other hand, molnupiraivr has the advantage of being an oral tablet that can be taken outside of a clinical setting compared to the different experimental treatments so far, reducing the risk of overwhelming hospital capacity. Furthermore, it is much more affordable as it costs only around $700 per person, but the cost is still likely to limit its use. Nonetheless, Dr. Shaw says, “it certainly has the potential to be a really important advance.” “Other COVID-19 treatments, such as remdesivir or monoclonal antibodies against the SARS-CoV-2 virus causing COVID-19, are given intravenously. This is a pill your physician could write a prescription for, that you could pick up in a drugstore,” he adds.
Doctors have stressed that if and when molnupiravir is authorized, and even if it is as effective as it was in the study, vaccines would still remain key to prevent and reduce the spread of COVID-19. They claim that those who have been vaccinated have a significantly lower chance of being ill and requiring treatment. “Some people might say, ‘I'm not getting vaccinated because I'll have access to these medications’—to this pill or to remdesivir or other treatments. But you can’t trade one for the other. If you haven’t done so already, the most important thing is still to get the vaccine," says Dr. Jamie Meyer, a Yale Medicine infectious diseases specialist.
In a CNN article by Kent Sepkowitz, a physician and infection control expert at Memorial Sloan Kettering Cancer Center in New York, discusses how it is necessary to take a step back and analyze prospects. As much as some people despise vaccines, many despise pills just as much. Adherence is lower when a pill is given twice a day than a once-daily pill, even in short courses like the one planned for monupiravir (four pills twice a day for five days). There are also other issues with pills, including side effects, cost, drug resistance, pregnancy use, and, most importantly, practicality.
Antiviral pills could save those who have never got vaccinated, provide overwhelmed hospitals with relief, and significantly benefit developing nations left behind. It is inevitable that if this groundbreaking treatment gets authorized, there will be other obstacles we would have to face. Merck’s pill may or may not be a game-changer, and its success will ultimately depend on whatever happens in the pandemic. However, one thing is for certain is that antiviral pills advance our fight against the pandemic.
Article Author: Tanya Kor
Article Editors: Stephanie Sahadeo, Edie Whittington