By MATTHEW PER­RONE-As­so­ci­at­ed Press 

WASH­ING­TON (AP) — As more doc­tors pre­scribe Pfiz­er’s pow­er­ful COVID-19 pill, new ques­tions are emerg­ing about its per­for­mance, in­clud­ing why a small num­ber of pa­tients ap­pear to re­lapse af­ter tak­ing the drug. 

Paxlovid has be­come the go-to op­tion against COVID-19 be­cause of its at-home con­ve­nience and im­pres­sive re­sults in head­ing off se­vere dis­ease. The U.S. gov­ern­ment has spent more than $10 bil­lion to pur­chase enough pills to treat 20 mil­lion peo­ple. 

But ex­perts say there is still much to be learned about the drug, which was au­tho­rized in De­cem­ber for adults at high risk of se­vere COVID-19 based on a study in which 1,000 adults re­ceived the med­ica­tion. 

WHY DO SOME PA­TIENTS SEEM TO RE­LAPSE? 

Doc­tors have start­ed re­port­ing rare cas­es of pa­tients whose symp­toms re­turn sev­er­al days af­ter com­plet­ing Paxlovid’s five-day reg­i­men of pills. That’s prompt­ed ques­tions about whether those pa­tients are still con­ta­gious and should re­ceive a sec­ond course of Paxlovid. 

Last week, the Food and Drug Ad­min­is­tra­tion weighed in. It ad­vised against a sec­ond round be­cause there’s lit­tle risk of se­vere dis­ease or hos­pi­tal­iza­tion among pa­tients who re­lapse. 

Dr. Michael Char­ness re­port­ed last month on a 71-year-old vac­ci­nat­ed pa­tient who saw his symp­toms sub­side but then re­turn, along with a spike in virus lev­els nine days in­to his ill­ness. 

Char­ness says Paxlovid re­mains a high­ly ef­fec­tive drug, but he won­ders if it might be less po­tent against the cur­rent omi­cron vari­ant. The $500 drug treat­ment was test­ed and OK’d based on its per­for­mance against the delta ver­sion of the coro­n­avirus. 

“The abil­i­ty to clear the virus af­ter it’s sup­pressed may be dif­fer­ent from omi­cron to delta, es­pe­cial­ly for vac­ci­nat­ed peo­ple,” said Char­ness, who works for Boston’s VA health sys­tem. 

Could some peo­ple just be sus­cep­ti­ble to a re­lapse? Both the FDA and Pfiz­er point out that 1% to 2% of peo­ple in Pfiz­er’s orig­i­nal study saw their virus lev­els re­bound af­ter 10 days. The rate was about the same among peo­ple tak­ing the drug or dum­my pills, “so it is un­clear at this point that this is re­lat­ed to drug treat­ment,” the FDA stat­ed. 

Some ex­perts point to an­oth­er pos­si­bil­i­ty: The Paxlovid dose isn’t strong enough to ful­ly sup­press the virus. Andy Pekosz of Johns Hop­kins Uni­ver­si­ty wor­ries that could spur mu­ta­tions that are re­sis­tant to the drug. 

“We should re­al­ly make sure we’re dos­ing Paxlovid ap­pro­pri­ate­ly be­cause I would hate to lose it right now,” said Pekosz, a vi­rol­o­gist. “This is one of the es­sen­tial tools we have to help us turn the cor­ner on the pan­dem­ic.” 

HOW WELL DOES PAXLOVID WORK IN VAC­CI­NAT­ED PEO­PLE? 

Pfiz­er test­ed Paxlovid in the high­est-risk pa­tients: un­vac­ci­nat­ed adults with no pri­or COVID-19 in­fec­tion and oth­er health prob­lems, such as heart dis­ease and di­a­betes. The drug re­duced their risk of hos­pi­tal­iza­tion and death from 7% to 1%. 

But that doesn’t re­flect the vast ma­jor­i­ty of Amer­i­cans to­day, where 89% of adults have had at least one shot. And rough­ly 60% of Amer­i­cans have been in­fect­ed with the virus at some point. 

“That’s the pop­u­la­tion I care about in 2022 be­cause that’s who we’re see­ing -- vac­ci­nat­ed peo­ple with COVID -- so do they ben­e­fit?” asked Dr. David Boul­ware, a Uni­ver­si­ty of Min­neso­ta re­searcher and physi­cian. 

There’s no clear an­swer yet for vac­ci­nat­ed Amer­i­cans, who al­ready have a hos­pi­tal­iza­tion rate far be­low 1%. 

That may come from a large, on­go­ing Pfiz­er study that in­cludes high-risk vac­ci­nat­ed peo­ple. No re­sults have been pub­lished; the study is ex­pect­ed to wrap up in the fall. 

Pfiz­er said last year that ini­tial re­sults showed Paxlovid failed to meet the study’s goals of sig­nif­i­cant­ly re­solv­ing symp­toms and re­duc­ing hos­pi­tal­iza­tions. It re­cent­ly stopped en­rolling any­one who’s re­ceived a vac­ci­na­tion or boost­er in the past year, a change Boul­ware says sug­gests those pa­tients aren’t ben­e­fit­ting. 

At a min­i­mum, the pre­lim­i­nary da­ta should be re­leased to fed­er­al of­fi­cials, Boul­ware said. “If the U.S. gov­ern­ment is spend­ing bil­lions of dol­lars on this med­i­cine, what’s the oblig­a­tion to re­lease that da­ta so that they can for­mu­late a good pol­i­cy?” 

CAN PAXLOVID BE USED TO HELP PRE­VENT COVID-19 IN­FEC­TION? 

Pfiz­er re­cent­ly re­port­ed that proac­tive­ly giv­ing Paxlovid to fam­i­ly mem­bers of peo­ple in­fect­ed with COVID-19 didn’t sig­nif­i­cant­ly re­duce their chances of catch­ing it. But that’s not the end of the sto­ry. Pfiz­er is study­ing sev­er­al oth­er po­ten­tial ben­e­fits of ear­ly use, in­clud­ing whether Paxlovid re­duces the length and sever­i­ty of COVID-19 among house­holds. 

“It’s a high bar to pro­tect against in­fec­tion but I’d love to see da­ta on how Paxlovid did against se­vere dis­ease be­cause it may be more ef­fec­tive there,” said Pekosz.