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THE NEW YORK TIMES
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SCIENCE science.org 12 NOVEMBER 2021 • VOL 374 ISSUE 6569 799L
ast week’s announcement by drug
behemoth Pfizer that its 5-day pill
regimen powerfully curbs many early
SARS-CoV-2 infections opens a new
chapter in the battle against the virus.
In a clinical trial that an independent
monitoring group halted early because the
experimental therapy appeared so effective,
it slashed hospitalizations by 89% among
those treated within 3 days of symptom on-
set. If Pfizer’s drug candidate passes muster
with regulators, it could join molnupiravir, a
pill recently developed by Merck & Co. that
received approval last week in the United
Kingdom, as the first oral medications
proved to stop COVID-19 from progressing
to severe disease.
Such antivirals, public health experts
and scientists say, could help a broad swath
of people, including the unvaccinated and
those who develop breakthrough infections
despite vaccination. If affordable enough—
a still unresolved question—the pills could
also act as a crucial safety net for low-
income countries that have struggled to
obtain vaccines and that have more limited
hospital resources.
The Pfizer antiviral is a protease inhibitor,
a well-studied drug class that targets key en-
zymes in many viruses and that has already
revolutionized the fight against HIV. “Thislooks like an oral medication that really
works,” says Oriol Mitjà, a physician-scientist
who studies and treats infectious disease in
Papua New Guinea and is affiliated with the
Germans Trias i Pujol University Hospital.
Although neither company has provided
much data publicly, Pfizer’s compound ap-
pears more effective than molnupiravir,
which has a different mechanism. Together,
however, the two antivirals could transform
the pandemic’s course. Although they “can’t
replace vaccines,” says Nahid Bhadelia, an in-
fectious disease doctor at Boston University,
they can help “our return to normalcy.”
As has been typical for drug and vaccine
companies throughout the pandemic, Pfizer
initially made only topline clinical results
available, and the work has not been peer
reviewed. In a press release, the company
reported that just three of 389 people, or
0.8%, who took the antiviral within 3 days
of testing positive for COVID-19 were hospi-
talized, compared with 27 out of 385, or 7%,
in the placebo group. Six out of 607 who be-
gan the antiviral within 5 days, or 1%, were
hospitalized, versus 41 out of 612, or 6.7%, on
a placebo. Ten patients who got the placebo
subsequently died; no one on the Pfizer pill
did. Side effects were mild.
All the trial participants were un-
vaccinated and had at least one medical con-
dition that put them at higher risk of severe
COVID-19. The antiviral is also being testedin lower risk people, including those who are
vaccinated, and in uninfected people with a
household member positive for the virus, to
see whether it stops the former from devel-
oping COVID-19 symptoms. The company
plans to seek authorization in the United
States and elsewhere as soon as possible.
Affordable and easily administered
COVID-19 treatments are desperately
needed. Only one class of therapy for early-
stage COVID-19 is authorized in the United
States: monoclonal antibodies, which block
surface proteins of the coronavirus and
slow SARS-CoV-2 from infecting cells. But
the price tag (about $2000 per dose, a cost
currently paid in the United States by the
federal government), scarcity, and the need
to infuse or inject them have slowed their
use in wealthy countries, let alone develop-
ing nations.
Molnupiravir, licensed by Merck from
Ridgeback Biotherapeutics, tricks SARS-
CoV-2 into incorporating the compound
into its genetic information, causing muta-
tions that stop the virus from replicating.
The company announced last month that
a 5-day regimen cut COVID-19 hospitaliza-
tion by about 50%. Some scientists worry
the drug could cause mutations in people
or that, in the long term, widespread use of
the drug may create harmful viral variants,
but little evidence supports either concern so
far. To date, the United Kingdom is green-IN DEPTH
By Jennifer Couzin-FrankelCOVID-Antiviral pills could change pandemic’s course
Strong showing for Pfizer protease inhibitor follows success for Merck’s molnupiravir
A new antiviral dramatically reduced the number of people recently diagnosed with COVID-19 who needed hospitalization.