Two COVID-19 antivirals get FDA nod for emergency use

Paxlovid is not recommended for patients with severe kidney or liver disease, and if given to people with uncontrolled or undiagnosed HIV infection may result in HIV drug resistance. Molnupiravir is not recommended for use during pregnancy as the drug may harm the foetus.

If full vaccination with any of the COVID-19 vaccines greatly reduces the risk of progressing to severe disease and death, the recent emergency use authorisation granted by the U.S. FDA to two oral antiviral drugs for certain categories of people who are likely to become severely ill provides the much-needed fillip to fight the disease and prevent deaths.

Unlike in the case of remdesivir, both the drugs — Pfizer’s paxlovid and Merck’s molnupiravir — are oral pills and so can be administered outside hospital settings. These drugs are meant to be used in people with mild-moderate disease within five days of symptom onset. The antiviral drug paxlovid, the first to be granted an EUA on December 22, has been greenlighted for use above 12 years, while the EUA granted the next day for molnupiravir is for use only in those above 18 years.

The approval for the antivirals comes at a time when two monoclonal antibody treatments from Regeneron and Eli Lilly are no longer effective against Omicron.

Paxlovid has 88% efficacy in preventing COVID-19-related hospitalisation or death, while molnupiravir has only 30% efficacy in achieving the same endpoint; the efficacy of molnupiravir dropped from 50% during interim analysis to 30% in the final analysis of the trial data.

Safety profile

Paxlovid is not recommended for patients with severe kidney or liver disease, and if given to people with uncontrolled or undiagnosed HIV infection may result in HIV drug resistance. Molnupiravir is not recommended for use during pregnancy as the drug may harm the foetus. FDA also noted in its EAU approval advised sexually active males with partners of childbearing potential to use contraception during molnupiravir treatment and continue doing so for at least three months after the last dose. Females of childbearing potential too were advised to use birth control during treatment with molnupiravir and for four days after the last final dose. The FDA specifically mentions that molnupiravir is recommended when “alternative treatment options are not accessible or clinically appropriate”. Both the pills are likely to work against the Omicron variant.

The biggest gainers will be the immunocompromised people who may lack sufficient immune protection despite being fully vaccinated. Antivirals can never substitute vaccines and hence every eligible individual should get fully vaccinated as soon as possible, particularly in light of the highly transmissive Omicron variant spreading in many countries. Since treatment should begin within five days of symptoms onset, access to testing and turnaround time should be vastly improved. At the same time, indiscriminate use of the drugs should be avoided at any cost as this will not only cause complications for individual patients but also lead to drug resistance.

Easy access to generic drugs

Unlike in the case of COVID-19 vaccines where access and availability have become a major sore point for many low- and middle-income countries, both the drugs will be far more freely accessible to many of these countries. This is because of the agreement that the companies have reached with the Medicines Patent Pool.

As per the agreement, generic manufacturers are permitted to produce and supply the paxlovid drug to 95 low- and middle-income countries, while access to the generic version of molnupiravir will be to 105 countries. India will be able to manufacture generic versions of both the drugs and supply them to the approved countries as well as access them here at less price.

Yet, not all middle-income countries will have access to generic versions of the drugs as upper-middle-income countries have been excluded. This will prevent many of such countries from freely accessing affordable, live-saving drugs during the pandemic.

With increased coverage of vaccination and easier availability of treatment, the world will be better placed to deal with the fast-mutating virus.

Published in The Hindu on December 25, 2021