Mixed picture emerging for antiviral COVID-19 pills
Drugs would be taken multiple times a day, in place of monoclonal antibody infusions.
ROCHESTER, Minn. -- With the pending arrival of antiviral pills for COVID-19 by drugmakers Merck and Pfizer, a mixed picture is emerging over the place of at-home medicine in the pandemic.
Merck's antiviral is called molnupiravir, and it is a series of 40 pills taken over five days. According to company-reported results, molnupiravir reduced risk of hospitalization and death by 30%.
Though it is thought to be relatively inexpensive to manufacture -- global health officials hope the series can be sold for as little as $10 in areas of need -- the federal government has purchased an initial supply of the drug at $700 per treatment.
"Molnupiravir induces hypermutation of the virus," says Mayo Clinic infectious disease specialist Dr. Andrew Badley. "When the virus replicates, it makes errors in the replication ... which means it can't work."
Badley says this mechanism raises theoretical concerns for pregnant women, and that "molnupiravir might drive the emergence of different virus strains ... We just don't yet know what the effect will be in our population."
The Food and Drug Administration advisory committee voting on molnupiravir split on a 13 to 10 vote. The committee expressed concern with the drug's low efficacy when monoclonal antibody alternatives at 90% effectiveness were available.
Pfizer's antiviral is called Paxlovid and patients prescribed the drug take six pills a day for five days. Company-reported results suggest it has three times rate of effectiveness as molnupiravir, at almost 90%.
"Paxlovid blocks protease," says Badley, "which is a necessary enzyme in the life cycle of the virus." Badley says Paxlovid "took advantage of the past several decades of enhanced understanding ... of protein structure."
The purpose of antiviral agents is to reduce the progression of illness within newly diagnosed unvaccinated persons at risk of poor outcomes from COVID-19.
One liability to the antivirals is their dependency on a cheap, accessible, fast and robust COVID-19 testing system, a resource which does not exist in the U.S. at this time. The drugs are only as good as a patient's ability to quickly know if they are infected.
Complicating the picture faced by these new treatments is the arrival of the omicron variant, which has a high number of mutations on the spike protein. Since neither of the new antivirals targets the spike protein, they possess an advantage of being considered unaffected by the arrival of the mutant strain.
MRNA vaccinations for COVID-19 are focused on spike protein, but it's not clear if the mutations in omicron have affected their effectiveness.
The pills would be added to an antiviral arsenal that has included monoclonal antibody infusions made by Lilly, Regeneron and Glaxo, as well as Remdesivir by Gilead.
Infusions require one hour-long visit to participating infusion centers. If taken early enough, they generally have a good record of protection from serious illness.
Rural areas and underdeveloped countries do not have access to infusion centers, however. Those areas also have some of the lowest vaccination rates. Those characteristics makes these prime locations for antiviral care in pill form.
Historically, antiviral pills are considered a second-tier solution for health officials, with vaccines at the top. This is because vaccinated persons who test positive have a vaccine-mediated immune response to keep them out of the hospital, and the vaccines have shown themselves highly effective at doing just that, even in the case of breakthrough infections.
Antivirals are also seen as valuable in the care of immunocompromised persons who have tested positive for COVID-19, given the weakness of the vaccine for those with such conditions.
"What I believe will happen as the oral antivirals get authorized is that it will help mitigate demand," said Mayo Clinic's Dr. Raymund Razonable, who is director with the clinic for monoclonal antibody infusion research.
"There will be patients that will prefer oral over IV infusions, and that will lessen the burden for the inpatient facilities."
"They will be capturing the same population, and patients will now have a choice as to whether they go for the IV infusion or oral pills, depending on their preference."