TUESDAY,NOVEMBER 23 , 2021 .THEWASHINGTONPOST EZ RE A
saki, an immunologistatYale
UniversitySchool of Medicine,
sees combinationsof drugsas the
future—particularlyfor people
withcompromisedimmunesys-
temswhocanhavecovid-19infec-
tionsthatsimmerfor weeksor
months, allowingthe virus to
mutate.
“If we have acombination, an
antiviralcocktail,itmightprotect
againstthe emergence of these
mutations,”Iwasakisaid.
Iwasakiand colleaguesrecent-
ly reported apreprintcase study
of awoman in her 70s whose
cancer had weakened her im-
munesystem.Thepatient was
sick for six monthswithpersis-
tent covid-19, and during her
treatmentreceived acourseof
remdesivir,anintravenousanti-
viral medication. At first, her
fever resolvedand levels of the
virusdropped—until amutation
thatgavethe virus resistanceto
remdesivir allowed it to surgeand cocktailsthatcombinethem,
to avoid allowing the virus to
sneakpastthe protection given
by anyindividualtreatment.
“Six [treatments] at amini-
mum. Nine would be better.
Twelve would be even better,”
Dieffenbachsaid.“Weneed the
companiesto makethe drugsat
scale,as availableas aspirinand
Tylenol—metric kilotons.”
Both Pfizer and Merck have
begunscalinguptheirpillsbefore
theyhavereceivedaregulatory
greenlight.Pfizer plansto make
50 milliontreatmentcoursesin
2022.Merck projects having 10
milliontreatmentcoursesready
by the end of this year,and more
in 2022.TheUnited States has
pre-purchasedabout3.1million
treatment courses fromMerck
and 10 millionfromPfizer.
Thequestion now on many
scientists’ mindis how the virus
will respondas thosedrugsgo
into widespreaduse. AkikoIwa-changethe world, the worldmay
also have to change.
Alongsidemedicaltools,Dief-
fenbachis callingfor asocietal
shift—anew normalin which
people with respiratorysymp-
tomstestassoon as symptoms
appearand startdrugs within
threeto five days.
“WhatI’m advocating for is a
fundamental changeinap-
proach,”Dieffenbachsaid. “Inthe
future,we don’t requirepeopleto
go to thedoctor if they’re feeling
sick to gettested. There’s arapid
testyou do at home.People are
motivated to getaprescription,
or alreadyhave aprescriptionso
theycanstarttakingitrightaway.
That’s where we’regoing to have
to getto.”
Even as experts anticipate the
arrival of lifesavingdrugs,they
worry. Willpeopleuse the exis-
tenceofmedicinesasanexcuseto
avoid vaccination or boosters?
Will peoplewho could clearly
benefit—thosewhohaveavoided
the vaccines—seek out testing at
the firstsignofasore throatand
getaccess to drugs quickly
enough?
Doctors are hopeful thatpeo-
ple will realizethatavoidingsick-
ness altogether is the bestoption.
Boulwaresaid one colleagueputs
it this way: Syphilisis treatable
with penicillin.But it is far better
to not getinfected in the first
place.
“It’salmostlikeapplyingthe
correcttool for the task at hand.
Treatmentsare going to playa
backup roleto vaccines,”said
RajeshGandhi,an infectious-dis-
easesphysicianat Massachusetts
General Hospital.
Theexistence of treatments
couldalso triggerthe startofa
philosophicaldiscussionon how
to deal with sicknessitself.Before
the pandemic,peoplehoppedon
flightsand wentto schooland
work with runnynoses and
coughs.If peoplego backto old
habits,it maybehard to identify
and treatpeopleearlyenoughin
their illness.
“I don’t thinkwe’regoing back
to justignoringpeoplewho are
sick,”said LarryCorey, avirolo-
gistandpastpresidentoftheFred
Hutchinson Cancer Research
Center in Seattle. “Coming to
schoolorcomingtoworkandjust
assumingthatnomatterwhat,it’s
not going to hurtyou.”
[email protected]back.
In this case, the resistant virus
thatwas ableto thrivein the
presenceof remdesivirwasn’t go-
ingtotakeovertheworld—itwas
less adeptat multiplyingthan the
originalstrain. But the case illus-
trates the risk of newvariants
arisingafter treatment.
To protectimmunocompro-
misedpeople,othercompanies—
includingAstraZenecaand Ada-
gio Therapeutics—are trying
anotherangleof attack:laborato-
ry-brewed monoclonalantibod-
ies thathavebeen engineeredto
stick aroundin the bloodfor a
long time,with the idea thatthey
couldprovideashot of long-term
protection,similarto avaccine.
Regeneronrecentlyreleaseddata
showingthatitsmonoclonalanti-
bodycocktail,currentlyauthor-
ized as atreatmentfor people
infected or recentlyexposed,re-
mainsabout80 percenteffective
againstsymptomatic infections
eightmonthslater,bolsteringthe
case for its drugas apreventive
forpeoplewhodon’trespondwell
to vaccines.
“For us, vaccination has been
the jailbreaker; it has allowedus
to live life normally,” said Hugh
Montgomery, aprofessorof in-
tensivecare medicineat Univer-
sityCollegeLondonleading a
trialof the AstraZeneca drug,
whichhas been submitted to U.S.
regulators for emergencyautho-
rization.“My sister,who has
breastcancerand has justgot 18
weeksof chemotherapy and can’t
mountan antibodyresponseto
the vaccine—aswe’ve lifted our
lockdown,she’s becomeaprison-
er in her house.”
Instead of one drugor one
solution,therewill probablybe
treatmentniches—and the mar-
ketopportunityisn’t aone-time
flare;it’s whatpharmaceutical
executivescall “durable.”
On arecentearningscall, Pfi-
zer chiefexecutiveAlbertBourla
saidthathesees ayears-long
market for antiviral pills. As long
as the worldneedsvaccines,it
will also need treatments.
“Aslong as you have covid
around,you will have aneed to
vaccinate and protectand then
you will have aneed to treatand
save lives,”Bourlasaid.Arevolutionoutsidethe
medicinecabinet
Forcovid-19 treatments tohospital. Pfizer’s Paxlovid re-
ducedhospitalizationsand death
by an impressive89 percent,but
it mustbetaken withindays of
symptoms.
Andscientistshavelearnednot
to underestimate the virus.As
soon as treatmentsbecomewide-
spread,scientists will be watch-
ing for signsof resistance.
“There’s always asense of opti-
mismwithanew strategythat
comesalong,and I’moptimistic,
too, thatthisisone additional
thingthatisgoing to help in our
fight againstthisdisease,”said
EricaJohnson,chairof the Infec-
tiousDiseaseBoardof the Ameri-
can Boardof InternalMedicine
and aphysician at the Johns
HopkinsBayviewMedicalCenter.
“ButI’malso cautiousthatitis
justasinglestrategy, and it really
only worksif all the otherstrate-
gies are healthyand working,
too.”‘A good start,’not the end
CarlDieffenbach,director of
the Divisionof AIDSat the Na-
tionalInstitutesof Health,has
spentdecadesbattling adifferent
virus,overseeinga$1billionglob-
al researchportfoliofocusedon
HIV.Althoughthelongquestfora
vaccinehas beenunsuccessfulso
far,the diseasehas beentrans-
formedby treatmentsand pre-
ventionstrategies. Now, he is
trying to apply some of that
thinkingto covid-19.
No oneiswilling to outlinea
minimum thresholdoftreat-
mentsneededagainstavirus that
has beenso continuallysurpris-
ing,but whenpressed,Dieffen-
bachsays thatcoronavirustreat-
mentsthatwillsoon be reviewed
by regulators are “a good start” —
not the end.
It’s important to buildan ar-
senalof drugsthatuse different
techniquesto stop the virus.One
class of drugscan blockthe coro-
navirusfromenteringcells,as
monoclonalantibodiesalreadyin
use are designedto do. Another
class, likePfizer’sdrug,could
interferewithproteases,enzymes
thatthe virus uses to processits
proteins.Athird, likeMerck and
Ridgeback’smolnupiravir,could
interfere with adifferentenzyme
the virususes to makecopiesof
itself.
Dieffenbachthinksall three
anglesof attack will be needed,as
well as backupsfor each strategyback Biotherapeuticssafe and ef-
fective in comingweeks,as most
peopleexpect, the drugscould
makegetting sick far less scary.
TheUnitedStates has already
pre-purchasedmillionsof treat-
ments.Thegoodnewsarriveslike
an echoof lastyear,when two
remarkably effective vaccines
wereauthorizedin the middleof
the holidayseasonas awinter
surgeinnew casesloomed.
Butthese treatments alone
aren’tlikelytoclose the bookon
the coronavirus. Instead, they
will be avaluable additionto an
armamentariumthatthe worldis
going to have to keep building
and maintainingin the long run:
vaccines,booster shots,morean-
tiviral pills,virus-fightinganti-
bodies engineered to stick
around in people’s bodies and
fast-turnaroundtesting linked to
treatmentoptions.
“It’sahugepartofthe toolbox;
if we can moveeverythingup-
stream,instead of trying to treat
hospitalizedpatientswithlate-
stageseveredisease,”said David
Boulware, an infectious-disease
physician at the Universityof
MinnesotaMedicalSchool.“I’m
an optimist. Six months from
now,Ithinkthingsaregoingtobe
great.”
Drugs thatcan be taken at
hometo keep mildlysick people
fromendingup in the hospital
will be aturningpoint.But a
majorlessonof the pandemichas
been thataroundeach cornerare
morecorners.
Remember,the vaccineswere
better than anyone expected. But
morepeoplein the United States,
wherevaccinesareplentiful,have
diedof covid-19 in 2021, after
shotsbecameavailable,thanin
the year before.
Antivirals, too, will be power-
ful but won’t be aget-out-of-jail-
freecard by themselves.
Initially,theywillbeavailable
topeople at increasedrisk of
severe illnessdue to ageorother
factors. People will need to recog-
nizetheir symptoms early,get
tested and starttreatmentsright
away.
Thedrugs aregood, butnot
perfect: Merck and Ridgeback’s
molnupiravir slashed hospital-
ization and death rates by half in
aclinicaltrial,but thatmeans
somepeoplestill endedup in the
TREATMENTSFROMA
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