Merck, Pfizer COVID-19 Antivirals Different From Ivermectin

SciCheck Digest

Merck and Pfizer are each developing a new oral antiviral drug that might prevent or treat COVID-19. The pills are very different from the antiparasitic medication ivermectin, contrary to claims online that they are “suspiciously similar” or that the companies are “repackaging” ivermectin in a ploy to increase profits.

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Throughout the COVID-19 pandemic, there has not been an easy-to-take oral pill that can prevent or treat infection with SARS-CoV-2, the coronavirus that causes COVID-19. Pharmaceutical companies, however, have been working on testing novel drug candidates, and in the last few weeks both Merck and Pfizer announced developmental milestones.

On Sept. 27, Pfizer said that it was launching a late-phase clinical trial to test whether, in combination with another drug, its oral COVID-19 antiviral can prevent infection with the coronavirus. Dubbed PF-07321332, the investigational medication is a protease inhibitor that blocks a key enzyme the SARS-CoV-2 virus needs to replicate itself.

The company previously started phase 2/3 trials in July and August to test whether the drug combo works as a treatment in people with confirmed infection.

On Oct. 1, Merck and Ridgeback Biotherapeutics announced positive phase 3 trial interim results for their COVID-19 antiviral. Called molnupiravir, after Thor’s hammer, the pill reportedly cut the risk of hospitalization and death in people with mild to moderate COVID-19 by around 50% when given within five days of symptom onset, according to a press release. 

While the results have not been published or peer-reviewed, they were compelling enough for the trial’s independent Data Monitoring Committee to recommend an early halt to recruitment into the study. The companies announced on Oct. 11 that they had submitted their application for emergency use authorization of the pill to the Food and Drug Administration; the agency has said it will convene an advisory committee to discuss the application on Nov. 30.

Molnupiravir is a nucleoside analog — a drug that messes up viral replication by tricking the virus into using the processed medication as one of its building blocks for its genetic code. It’s a kind of molecular bait-and-switch operation that leads the virus to incorporate so many errors during replication that it cannot survive and propagate. This is what’s known as “error catastrophe,” using a mechanism called “lethal mutagenesis.”

Although both drugs are novel, with news of these developments, people on social media are spreading the false notion that the pills are the same or “suspiciously similar” to ivermectin — an antiparasitic medication that has not been shown to be effective against COVID-19 — because, they claim, the pharma companies want to drive up profits. (For more on ivermectin, see SciCheck’s article “Ongoing Clinical Trials Will Decide Whether (or Not) Ivermectin Is Safe, Effective for COVID-19.”)

“In other news, Pfizer is testing Ivermectin, now renamed PF-07321332, to help with Covid. They have done this so they can make this drug more expensive than Ivermectin, despite the fact, they are the same drug,” wrote one Twitter user, sharing a Reuters article about Pfizer’s COVID-19 prevention trial.

That tweet was labeled as sarcasm by its author, but it was nevertheless shared in a screenshot on Instagram, with the sharer falsely claiming that Pfizer was actually “attempting to reverse engineer a version of ivermectin that can’t quite legally be called ivermectin.”

Some iterations of the claim incorrectly posit that Pfizer’s drug is “based on” ivermectin and that the two are essentially the same because both are protease inhibitors — something that has not been established, and even if true, doesn’t mean the drugs are similar, as we’ll explain. 

“Pfizer’s new oral antiviral is just a protease inhibitor just like Ivermectin,” reads one such Instagram post, shared by Idaho state Rep. Tammy Nichols. “They’re literally repackaging ivermectin to sell to the masses with a new name.”

That post uses the phrase “Pfizermectin,” which may have originated on the conservative satire website the Babylon Bee in a parody drug advertisement posted to YouTube earlier in September.

Many of these social media posts, including a segment on Alex Jones’ InfoWars, directly share or draw on elements from articles published on ZeroHedge, a frequent source of misinformation.

The supposed connection, according to a computational modeling paper published by some Indian scientists in March, is that ivermectin might act as a protease inhibitor, among other potential mechanisms. This alleged connection is made explicit in social media posts with a graphic juxtaposing a Pfizer press release and the abstract of the Indian paper.

That paper, however, does not show that ivermectin acts as a protease inhibitor against SARS-CoV-2 through any sort of biological experiment — it only proposes the possibility based on computer simulations. 

The data so far do not support using ivermectin to treat COVID-19, although clinical trials are underway to find out for sure. But if the drug does work, it is likely not through protease inhibition or any other antiviral mechanism, as the dose needed to see antiviral effects in the test tube is much higher than the amount prescribed to people.

Similar claims have been made about Merck’s molnupiravir, which in a deal with the government will cost around $700 for each course of pills if it receives authorization.

“Looks like Merck is repackaging the ‘horse drug’ and making it much more expensive! It will be the ‘new’ treatment for C. in pill form,” reads one Facebook post, referring to ivermectin. “My guess is they changed the formula just a bit to rebrand and patent.”

The Food and Drug Administration has warned people against self-medicating with easier-to-access formulations of ivermectin for livestock, which are highly concentrated and also may include other ingredients that have not been tested in people. The agency is aware of multiple cases in which people have consumed these products in an effort to treat or stave off a coronavirus infection and have needed to be hospitalized.

New Antivirals Nothing Like Ivermectin

Neither of the investigational drugs are ivermectin, nor are they particularly similar, which is obvious when looking at the chemical formulas and structures of the compounds.

Whereas ivermectin is made of just three kinds of atoms — carbon, hydrogen and oxygen — Pfizer’s drug also contains chlorine, nitrogen and sulfur; Merck’s drug also contains nitrogen, and its molecular weight is less than half that of ivermectin. Structurally, too, the drugs bear no resemblance.

“Pfizer’s 3CL protease inhibitor is nothing like ivermectin,” Dr. David Boulware, an infectious disease specialist at the University of Minnesota, told us in an email.

Ivermectin, which is sold by Merck under the brand name Stromectol, is FDA-approved to treat the parasitic conditions roundworm and river blindness in humans. The medication, which has been around for decades, works for this purpose by activating certain receptors on the cells of the parasites, which kills them.

Ivermectin was identified as a potential COVID-19 drug because it was found by some Australian researchers to inhibit replication of SARS-CoV-2 in cells grown in culture in the lab. Since it is cheap, and in human formulations, already safely used against parasites, it would be ideal if it could be repurposed as a COVID-19 treatment. 

Many drugs, however, can show antiviral effects in a petri dish, but prove worthless as medications. And in fact, ivermectin has repeatedly shown it can act against a variety of viruses in cultured cells, but it has not successfully panned out as a treatment for any viral disease.

Several mechanisms have been proposed for how ivermectin limits coronavirus replication in cells in the lab, but protease inhibition, as is claimed in social media posts, is not generally one of them.

More often, scientists — including the Australians who first published on the drug — cite the drug’s potential ability to prevent a host protein from importing viral proteins into the nucleus, or, more rarely, to interfere with SARS-CoV-2’s ability to use its spike protein to enter human cells.

But studies have also shown that the concentration of ivermectin that inhibits the coronavirus in a lab is much higher than that used in humans, making it unlikely that the drug, if it offers any benefit to COVID-19 patients, works as an antiviral. That’s in sharp contrast to the Merck and Pfizer drugs.

“While one could debate the exact mechanism of ivermectin, the biggest difference is that pfizer’s protease inhibitor inhibits coronavirus at concentrations that are achievable in the human body,” said Boulware, who is an investigator on a clinical trial at the University of Minnesota evaluating ivermectin as an outpatient COVID-19 treatment. “In the initial lab experiments, ivermectin required 50-100x the achievable concentrations in humans.”

A study of hamsters infected with the coronavirus and treated with ivermectin did not show a reduction in the viral load of the animals, but they were better able to smell, as measured in a food-finding test, and there was a positive effect on the inflammatory response. Boulware said that the results might suggest a possible benefit, but not for ivermectin as an antiviral.

As a result, there is no basis for claiming that either the Pfizer or Merck drugs are similar to ivermectin in any way.

Pfizer also denies any connection. “Pfizer’s protease inhibitor is not similar to that of an animal medicine and is not the same mechanism,” a company spokesperson said in an email, noting that protease inhibitors exist for a variety of viruses, including HIV and hepatitis C virus.

The company says its drug is the “first orally administered coronavirus-specific investigational protease inhibitor to be evaluated in clinical studies,” and was created in parallel with its investigational intravenous COVID-19 protease inhibitor. That drug, which is also undergoing testing, is an optimized version of a compound the company previously identified in 2003, when it was looking for medicines that could work against the first SARS coronavirus.