Paxlovid vs molnupiravir: How do Pfizer and Merck’s COVID pills compare?

Paxlovid and molnupiravir are being touted as breakthrough medications against coronavirus by their respective developers: US pharma giants Pfizer and Merck. While Merck says that molnupiravir is the “first oral antiviral medicine authorised for the treatment of mild-to-moderate COVID-19,” Pfizer claims that Paxlovid “would be the first oral antiviral of its kind” based on its mechanism of action against the infection. Pfizer said on November 5 that Paxlovid “significantly reduced hospitalisation and death” among non-hospitalised adult Covid-19 patients who are at high risk of developing severe symptoms.

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Paxlovid trial data, according to Pfizer, had displayed “overwhelming efficacy” and the company on November 16 applied for emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for Paxlovid.

HOW DOES IT COMPARE WITH THE MOLNUPIRAVIR?

The United Kingdom became the first country to approve molnupiravir for COVID-19 treatment on November 4 and Merck is awaiting a nod from the FDA after its Antimicrobial Drugs Advisory Committee meets on November 30 to discuss emergency authorization for the COVID-19 pill.

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The final trial results of both pills are yet to be released, even though trial findings have shown Paxlovid reduced the risk of hospitalisation or death by 89% in non-hospitalised high-risk adults as compared with the placebo group. Pfizer said that the overall study showed that over a period of 28 days, no deaths were reported in patients who received Paxlovid as compared to 10 deaths in patients who received a placebo.

The molnupiravir trial showed the pill reduced the risk of hospitalisation or death by about 50% as compared to the placebo group. The company said that through Day 29, no deaths were reported in patients who received molnupiravir, as compared to eight deaths in patients who received placebo. Merck, too, was advised by US regulators to halt trials thanks to its “positive results.”

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Molnupiravir and Paxlovid  Dosage

For molnupiravir, a dose of 800 mg twice daily for 5 days was recommended for Phase II evaluation. Paxlovid treatment consists of three pills twice daily for five days, albeit in combination with a low dose of ritonavir, an HIV antiviral that can boost the level of other protease inhibitors.

Molnupiravir vs Paxlovid: How do they work?

Paxlovid works by blocking the SARS-CoV-2 protease that the virus needs to replicate. Molnupiravir introduces errors in the RNA replication mechanism, rendering the virus incapable of producing copies of itself once it has infected an individual. Both drugs have been designed to be given at the first sign of illness at home to avoid serious illness or death.

Pfizer said that Paxlovid has to be prescribed “at the first sign of infection or at first awareness of an exposure” while regulators in the UK — where molnupiravir will be marketed under the trademark Lagevrio — said while clearing molnupiravir that it is most effective when taken during the early stages of infection and, hence, is recommended for use “as soon as possible following a positive Covid-19 test and within five days of symptoms onset.”

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Molnupiravir and Paxlovid Availability 

Low-cost versions of paxlovid and molnupiravir could soon be available to billions of people, especially in low-income countries, thanks to a voluntary licensing agreement signed by UN-backed public health organisation Medicines Patent Pool (MPP) with Pfizer and Merck.

Pfizer announced on November 15 it will “sub-licence” the production of paxlovid to generic drug manufacturers, while Merck last month said that it had agreed to share the license for molnupiravir.

Both Merck and Pfizer have entered into supply and advance purchase agreements for the COVID-19 pills with governments worldwide.