Pharmaceutical giants Pfizer and Merck have developed new COVID-19 drugs that could become a part of the tools used by physicians to treat COVID. Because of the importance of these drugs, both companies are seeking Emergency Use Authorizations (EUA) from the US FDA to get them in the hands of physicians as quickly as possible.
I have previously written about the Merck drug, molnupiravir, which will go by the trade name of Lagevrio. The Pfizer drug is called PF-07321332, with the trade name Paxlovid. Both drugs are purpose-developed anti-viral medications that have shown strong effectiveness against SARS-CoV-2, the virus that causes COVID-19. These are real antiviral drugs that were developed to treat COVID-19, unlike horse dewormers that have no effect against COVID-19.
This article will be in the form of a simple chart so that you can quickly see the advantages and disadvantages of both Pfizer and Merck COVID-19 drugs. I hope you find this helpful, and drop a note in the comments if you want me to add or change any information.
What are these drugs?
Before I give you the chart, I’d like to spend a bit of your time explaining the pharmacology of each. Not only will it tell you how these drugs work, but how real science develops real treatments for viral diseases.
Scientists don’t throw every chemical that they can find at diseases to see which works. In fact, they examine the pathophysiology of the disease, sometimes and the biomolecule level, to find weak points that can be exploited by a drug.
In each case, scientists looked for methods to stop the replication of the SARS-CoV-2 virus, which Merck and Pfizer scientists developed. They didn’t throw some chemicals at the virus, they examined the pathways that these viruses took to replicate in the body.
For the Pfizer drug, scientists developed an active 3CL protease inhibitor. Coronaviruses, like SARS-CoV-2, make use of proteases to cleave the glycoprotein structure of the virus so that it builds and replicates itself properly. If you can stop these proteases, the virus is then unable to replicate itself. Protease inhibitors have been used as anti-viral drugs for decades – many HIV and hepatitis C medications use this mechanism.
The Merck drug went about this in a different way. Molnupiravir is a synthetic nucleoside derivative, N4-hydroxycytidine, and exerts its antiviral action through the introduction of copying errors during viral RNA replication. Molnupiravir was originally developed for the treatment of flu, but because both influenza and coronaviruses use mRNA for replication, so it could be effective on each. Again, this does not mean that the influenza virus is closely related to coronaviruses, they aren’t, it just means they use a similar method to replicate itself.
Each of these COVID-19 drugs from Pfizer and Merck attempt to solve the same problem using slightly different biochemical methods — blocking viral replication.
But I want to remind the reader, which I will do several times — this is not a replacement for vaccines. Vaccines are cheaper (much cheaper, since these drugs will probably only be given once you are in the hospital with COVID-19) and are more effective. To paraphrase Benjamin Franklin, “a gram of prevention is worth a kg of cure.”
Pfizer and Merck COVID drugs comparison
| Paxlovid (PF-07321332) | Lagevrio (molnupiravir) | |
|---|---|---|
| Company | Pfizer | Merck |
| Co-developer | None | Ridgeback Biotherapeutics |
| Mechanism of action | Active 3CL protease inhibitor | Synthetic nucleoside derivative, N4-hydroxycytidine |
| Second medication | Ritonavir, which is made by AbbVie, must be taken with Paxlovid | None |
| Clinical trial design | Unvaccinated people with mild to moderate Covid-19 and at least one risk factor for severe disease. Drug was taken within three days of first symptoms. | Unvaccinated people with mild to moderate Covid-19 and at least one risk factor for severe disease. Drug was taken within five days of first symptoms. |
| Clinical trial size | 385 patients in the placebo group, and 389 in the group group that received the medicines | 1300 patients divided between placebo and medicine |
| Effectiveness | Reduced the risk of hospitalization and death by 89%. | Reduced the risk of hospitalization and death by 50%. |
| Effectiveness against death | 100% | 100% |
| Dosages | 3 pills, 2X per day for 5 days | 4 pills, 2X per day for 5 days |
| Timing | Medication must be taken within three days of first symptoms and confirmation of COVID-19 infection. Effectiveness drops after three days. | Medication must be taken within three days of first symptoms and confirmation of COVID-19 infection. Effectiveness drops after three days. |
| Safety | No detailed information at this time, more will be available when the expert committee reviews the EUA application. However, Pfizer claims that there was no difference in adverse effects between the placebo and drug groups. | No detailed information at this time, more will be available when the expert committee reviews the EUA application. However, Merck claims that there was no difference in adverse effects between the placebo and drug groups. |
| Can the drugs be taken in combination? | Unknown. No testing was performed combining the two drugs. | Unknown. No testing was performed combining the two drugs. |
| Can the drugs be given to vaccinated individuals with breakthrough infections? | Unknown. All clinical trial participants were not vaccinated. Pfizer has a clinical trial underway testing the drug on vaccinated individuals. The FDA and CDC will probably need to make recommendations in the future. | Unknown. All clinical trial participants were not vaccinated. The FDA and CDC will probably need to make recommendations in the future. |
| Cost? | Pfizer has not set a price at this time. It probably will be the same as Merck, $700 for a five day course of treatment. | Merck has an agreement with the US government to charge $700 for the five day course of treatments. The cost for people outside of the USA will probably pay a different amount. |
| Availability? | Medications in pill form are easier to manufacture and distribute than biologics like vaccines and monoclonal antibodies. The drugs should be readily available after receiving EUA. | Medications in pill form are easier to manufacture and distribute than biologics like vaccines and monoclonal antibodies. The drugs should be readily available after receiving EUA. |
| Will it have an effect on patient DNA? | No. | As with mRNA vaccines, there might be claims that this drug will have an effect on the patient’s DNA. There are negligible risks that any changes to the viral mRNA will have an effect on the host DNA. However, there is a peer-reviewed published study in mammalian cell culture that it might have an effect. |
| Cancer patients? | These drugs have the potential to interfere with many therapies used to treat cancer. | These drugs have the potential to interfere with many therapies used to treat cancer. |
| Is the drug a replacement for vaccines? | No. The vaccine is more effective and probably more safe. | No. The vaccine is more effective and probably more safe. |
Summary
Both of these COVID-19 drugs from Pfizer and Merck are highly effective for treating COVID-19 if given within three days of onset of symptoms. This can be problematic given how slow testing for the disease can be — the drugs will not be approved for prophylactic use, so they can only be given if the disease is confirmed.
Despite the apparent differences in effectiveness, we should not compare the numbers. Those are two different clinical trials, and it is bad science to compare the results in one trial to a completely different one. My guess is that in a head to head clinical trial, the effectiveness will probably be similar.
Otherwise, there isn’t much to choose between the two drugs. I’m a tiny bit concerned about the DNA issue with molnupiravir, but I’m not a fan of mammalian cell culture preclinical studies being used to make broad clinical pronouncements. It bears watching, however. And I’m sure the FDA expert committee will discuss it at length.
This chart will be updated as more data is provided to us when the documents are posted for the FDA expert review meeting.
And one more thing — getting the COVID-19 vaccines is much more important.
Citations
- Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung SH. An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J Med Chem. 2016 Jul 28;59(14):6595-628. doi: 10.1021/acs.jmedchem.5b01461. Epub 2016 Feb 29. PMID: 26878082; PMCID: PMC7075650.
- Toots M, Yoon JJ, Hart M, Natchus MG, Painter GR, Plemper RK. Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model. Transl Res. 2020 Apr;218:16-28. doi: 10.1016/j.trsl.2019.12.002. Epub 2019 Dec 25. PMID: 31945316; PMCID: PMC7568909.
- Toots M, Yoon JJ, Cox RM, Hart M, Sticher ZM, Makhsous N, Plesker R, Barrena AH, Reddy PG, Mitchell DG, Shean RC, Bluemling GR, Kolykhalov AA, Greninger AL, Natchus MG, Painter GR, Plemper RK. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci Transl Med. 2019 Oct 23;11(515):eaax5866. doi: 10.1126/scitranslmed.aax5866. PMID: 31645453; PMCID: PMC6848974.
- Zhou S, Hill CS, Sarkar S, Tse LV, Woodburn BMD, Schinazi RF, Sheahan TP, Baric RS, Heise MT, Swanstrom R. β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells. J Infect Dis. 2021 Aug 2;224(3):415-419. doi: 10.1093/infdis/jiab247. PMID: 33961695; PMCID: PMC8136050.
