How Do Merck and Pfizer’s COVID Pills Compare?

As COVID-19 cases continue to surge, public health officials and researchers are looking for every tool to fight the virus. While vaccination should be the first line of defense, recently developed or repurposed antiviral medications may now offer treatment options as well.

While some treatments already exist like remdesivir—which utilizes monoclonal antibodies to combat the virus—they require hospitalization. New antivirals by Merck and Ridgeback Therapeutics and Pfizer are taken orally, which could lessen the strain on hospital systems.

Neither one of the drugs is currently approved by the Food and Drug Administration (FDA) for use in the United States, but both have earned emergency use authorization to treat COVID-19.

So how do these two pills compare? The Merck and Pfizer antivirals are comprised of very different pharmaceuticals, with extremely different efficacy rates.

Ramzi Yacoub, PharmD, chief pharmacy officer at SingleCare, told Verywell that while the drugs do essentially the same thing, they attack different parts of the virus.

"Merck’s polymerase inhibitor 'tricks' an enzyme so that it can’t be replicated properly and can’t survive," Yacoub said. "Whereas, Pfizer’s Paxlovid is a protease inhibitor that blocks an enzyme that is needed for the coronavirus to replicate.”

How It Works

Merck

Merck's molnupiravir was originally developed to combat viral Venezuelan equine encephalitis (VEE), a mosquito-borne disease. It was later found to also be effective against a virus in the coronavirus family, Middle East Respiratory Syndrome (MERS). The drug is considered a polymerase inhibitor since it targets ribonucleic acid polymerase.

As the RNA polymerase duplicates, molnupiravir introduces fatal errors in the code, causing the virus to mutate to the point of death.

In the largest trial of the pill, molnupiravir was 30% effective at reducing hospitalization. Numbers climbed as high as 48% in smaller sample sizes in interim trials, but final numbers have settled.

Pfizer

Paxlovid combines two protease inhibitors for its virus attack. Ritonavir is an existing drug used to combat HIV. Nirmatrelvir is the brand name given to the experimental molecule PF-07321332, which was developed to specifically attack the protease of the COVID-19 virus.

While Nirmatrelvir attacks the protease of COVID-19, ritonavir attacks the enzymes that would take on Nirmatrelvir, operating as a team to slow the replication of the virus.

Paxlovid has had significantly more success than Merck's pill in clinical trials. Pfizer reported that the final analysis of the pill showed that the drug reduced risk of hospitalization or death by nearly 90% in unvaccinated adults when taken within three days of symptom onset.

In a separate trial with vaccinated adults, Paxlovid reduced hospitalization by 70% and eliminated deaths compared to a placebo.

Daniel Chancellor, thought leadership director at Informa Pharma Intelligence, told Verywell that finding a unique molecule may be why Paxlovid has such strong results.

"This one drug has been specifically designed and tailored and optimized pharmacokinetically optimized for oral delivery against a specific protease for SARs-CoV-2," Chancellor said. "This is a drug that's designed for this particular virus, so that may be why the efficacy is so impressive."

Omicron and Effectiveness

Preliminary research suggests both Merck and Pfizer's drugs should retain efficacy against the rapidly spreading Omicron variant. Omicron is defined by the 30 mutations on the spike protein, but only one of those mutations changes the way that either molnupiravir or Paxlovid attacks the virus.

Who Should Take Them

Both drugs were tested on unvaccinated adults with at least one comorbidity such as obesity, age (over 65), diabetes, or heart conditions. The drugs need to be administered within five days of symptom onset for the maximum effect.

Both molnupiravir and Paxlovid are only appropriate for mild to moderate cases of COVID-19, as diagnosed by a physician.

Dosage

Merck

Molnupiravir's full protocol is daunting—with a total course of 40 pills over the course of five days. Each pill delivers 200 mg of the active ingredient. The pill is only recommended for adults over the age of 18 and should be administered within five days of symptoms appearing.

Pfizer

Paxlovid consists of two pills of the COVID-19 specific Nirmatrelvir, and one pill of an existing drug used to treat HIV, ritonavir. All three of the pills are taken twice daily for five days. Paxlovid has the best results when taken within three days of symptom onset.

Side Effects

Merck

While molnupiravir is shown to reduce hospitalizations and deaths from COVID-19, it's not without its side effects.

Beyond any physical side effects, a small study published in The Journal For Infectious Diseases showed that while it used mutagenesis to combat the virus, that same mutagenic effect could cause cancer or birth defects in developing fetuses.

The potential for birth defects may be part of the hold-up in receiving authorization. Concern about the potential for birth defects for pregnant women and even their male partners was presented at the initial FDA approval presentation, but many are concerned that the drug may also open the door for further mutation of the SARS-CoV-2 virus itself.

"There is as well the viral variant generating potential, which is not a risk at the individual level, but as a risk at a global level," Chancellor said. "With other treatments being available, such as antibodies, and such as Pfizer's oral antiviral, it's something that needs to be very, very carefully considered. [We need to balance] the individual benefits of the patient versus essentially changing the course of the pandemic."

Pfizer

Pfizer has stated that side effects of Paxlovid are mostly mild but didn't disclose what they are.

Side effects of ritonavir, the HIV drug used in conjunction with Nirmatrelvir, are established and include:

• Diarrhea
• Nausea
• Vomiting
• Heartburn
• Dizziness
• Fatigue

There's no word as to whether those side effects are lessened or worsened by the interaction with Nirmatrelvir.

Authorization

Merck

The United Kingdom was the first country to authorized the use of molnupiravir. It will be available under the brand name Lagevrio. France has denied approval for the drug, citing low efficacy rates and high risks of mutagenicity.

Merck received authorization by the FDA in December 2021. The U.S. government announced that it had purchased 1.7 million doses of the drug as of June 2021.

Pfizer

Paxlovid earned authorization from the FDA one day before Merck. As of November 2021, Health and Human Services had already secured 10 million courses of the drug protocol.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.