Let’s start at the beginning. What exactly are these COVID pills and who are they for?
First, these drugs are not COVID-specific. They are antiviral drugs that theoretically can be used in many different viruses. Both Merck and Pfizer have developed pills you can take orally two times a day for five days. This makes them easier to use, distribute and store compared with intravenous drugs. They are intended for adults who are in the early stages of COVID-19, with mild to moderate symptoms and who are at risk of deteriorating and needing hospitalization – this includes older adults and those with pre-existing conditions. In both clinical trials, patients enrolled were unvaccinated and had at least one risk factor for severe infection, so it’s unclear if it can prevent breakthrough infection in vaccinated patients.
Trials are being held to test both drugs in low-risk patients and household exposures to see if they are of benefit.
How do they work?
Viruses are tricky to treat – they hijack a host cell and use it to replicate. So, it’s hard to interfere with the virus without causing collateral damage to human host cells, too. Viruses also mutate very quickly so treatments become less effective with time. Merck’s drug – molnupiravir – was originally developed to treat influenza. It works a lot like remdesivir, an intravenous drug used in hospitals to treat COVID. It is a nucleoside analog drug that inserts errors into COVID’s genetic code, disrupting its ability to spread. Theoretically, it only disrupts the virus genome, leaving the human cells alone. Pfizer’s drug is a protease inhibitor – similar to drugs used to treat HIV and hepatitis C. It blocks a protease enzyme that the virus needs to multiply but does not disrupt the genetic code of the virus. It is also taken in combination with an older HIV drug called ritonavir that helps the Pfizer pill remain in the body longer.
How effective are they?
As well as enrolling unvaccinated patients with at least one risk factor for severe infection, both clinical trials excluded those who are vaccinated and those who are low risk or exposed but not positive. It is important to understand who was in the trial so we can look at the numbers in context. For both drugs, the results appear promising for treating early COVID-19 and keeping patients out of hospital.
Pfizer’s preliminary results showed a reduction between 85-89 per cent in hospitalization and death compared to placebo. The drug worked better if you took it within three days of getting symptoms. Apparently, no one who took the drug died. The Merck pill reduced the risk of hospitalization and death in at-risk patients by 50 per cent when given within five days of the onset of symptoms.
The different designs and timing of the Pfizer and Merck trials make such comparisons imprecise. Side effect profile was very low in both trials. In fact, study volunteers who got the Pfizer pill reported a lower rate of side effects than those who received the placebo pill.
What are the limitations of these antiviral medications?
There are several.
The timing of taking the drug is a potential problem. The fact is they have to be taken within five days of the onset of symptoms, when they can be mild or minimally symptomatic. People can feel relatively well in these days, and we’ve told them not to seek medical attention if they are well. But this earlier part of the disease is where we need to intervene to get the best individual and community impact. We need to ramp up access to care and testing in milder cases for these drugs to work like they did in the trial.
The Merck pill was not tested in pregnant women and those who were breastfeeding. There is some concern this drug could interfere with RNA replication needed for fetus development and cause birth defects. The U.K., which authorized its use last week, recommended that it not be used in women who are pregnant, breastfeeding or who could become pregnant during treatment.
It has not been tested in children.
It has not been tested in those who were vaccinated or at low risk of hospitalization.
Finally, it has not been tested as a preventative therapy.
Are there any COVID antivirals currently approved for use in Canada?
There is one antiviral medication approved – remdesivir. But it can only be given intravenously. We’ve been using this drug for the past year. It was originally developed to treat hepatitis C and then used for other viruses, like Ebola. Neither of the Pfizer or Merck pills are approved in Canada yet. Merck submitted its request for approval to Health Canada on Aug. 13. It is still under review. Pfizer has not submitted its request for approval yet.
For those who are vaccine-hesitant, are these pills a potential substitute for the vaccine?
This pill is not a substitute for vaccination. Vaccines are not only cheaper, but they can also prevent infection from happening in the first place and can stop or slow transmission. Immunization remains our most important defence.
In contrast, the pills seem useful when someone is already infected and at high risk of getting severe COVID. They can reduce morbidity and mortality for that individual. These drugs have not been tested to prevent getting sick or as post-exposure prophylaxis. This may be the focus of subsequent trials.
What role could COVID pills play in this pandemic and beyond?
They fill in gaps in our COVID response. We’ve gotten to a saturation point of vaccine uptake in many places and the last 10-15 per cent will be the hardest to vaccinate. That is still a high enough number to drive numbers and keep the pandemic going. Unvaccinated individuals make up the majority of hospitalizations and deaths in Canada.
Having another tool to prevent death and sickness, especially at home before someone has to go to the hospital, is really promising. It is also quite a bit cheaper than giving monoclonal antibodies or intravenous drugs. And it can be used in places where vaccine access is lacking to reduce fatalities. Merck has tiered pricing and is licensing production for generic producers in India, meaning it could be quite accessible in countries where vaccine access hasn’t ramped up.
It’s really important to note that these drugs don’t reduce the need for us to take other measures. Wearing masks, social distancing and testing for COVID are still effective and necessary, and the arrival of an effective drug won’t be a reason to let our guard down. The existing pillars of pandemic response will remain crucial to keeping this disease in check.
However, because these antivirals are not COVID-specific, they may be used in other viral illnesses in the future.
Seema Marwaha is a general internal medicine physician, educator, researcher and journalist.
Editor’s note: Antiviral pills to treat COVID-19 are on the horizon for Canadians. The U.K. has authorized Merck’s molnupiravir for use while Pfizer plans to file its preliminary results for Paxlovid to the U.S. Food and Drug Administration by Nov. 25. Healthy Debate Editor-in-Chief Seema Marwaha answers your questions on the pills’ effectiveness, potential uses and limitations. This Q-&-A is adapted from a CBC interview broadcast on multiple CBC radio stations.
This article is republished from Healthy Debate under a Creative Commons license. Read the original article.