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How Pfizer developed a COVID pill in record time

Scientists at Pfizer's research and development laboratories in Groton, Conn., worked on the COVID-19 pill called Paxlovid.
Stew Milne
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Scientists at Pfizer's research and development laboratories in Groton, Conn., worked on the COVID-19 pill called Paxlovid.

Two new drugs are awaiting authorization from the Food and Drug Administration for treating patients with COVID-19, and both may be effective against the omicron variant.

One is made by Merck, the other by Pfizer.

The Merck drug has been in development for years. When the pandemic began, Pfizer's drug didn't exist. The story of its development is another example of how COVID-19 has sped up the drug and vaccine development process.

Pfizer wasn't starting exactly from zero. Mikael Dolsten, Pfizer's chief scientific officer, says that during the SARS outbreak in 2003, company scientists had begun to search for ways to combat that coronavirus.

In particular, they looked for proteins crucial for the virus to replicate once it infected someone.

Pfizer focused on protein virus needs for replication

One viral protein they focused on is called a protease. "We have learned that protease is a key regulator for the virus to unleash its machinery and hijack the human cells," Dolsten says.

Pfizer scientists thought if they could find a compound that would disrupt the protease, it would essentially stop the virus dead in its tracks.

That search petered out when the 2003 SARS outbreak passed. No disease, no market for a drug.

But Dolsten says the knowledge that was gained convinced them that a protease inhibitor would work to corral the coronavirus causing COVID-19.

They made computer models of the viral protease protein and assembled drug candidates that might block it.

"We actually had to design and synthesize some 600 unique chemical compounds," he says.

An old medicine helps the new drug work better

That was just the start. They had to test each compound to see how well it prevented the virus from infecting cells in the lab. Then they had to determine whether it would do the same thing in animals infected with the coronavirus. They also needed to find a candidate that would remain in someone's body long enough to have the desired antiviral effect. And they wanted to do all this fast.

"We put in place some very aggressive timelines where we made all of this happen over four months to come down to the optimal medicine," Dolsten says.

In the end, the drug developers had a candidate they thought would work. They mixed it in a pill with an old drug called ritonavir that extended the action of the protease inhibitor.

This past July, Pfizer began a study of people infected with the coronavirus who were at high risk of developing severe COVID-19. Half got the drug, called Paxlovid, within three to five days of the onset of symptoms, half a placebo.

Dolsten says the study was halted early because the drug appeared to be working. He says there was nearly a 90% reduction in hospitalization among people taking the new drug, "And 100% protection against death."

A similar analysis for the Merck drug found it lowered the risk of hospitalization or death by 50%. In a subsequent analysis presented to the FDA, the risk reduction fell to 30%, however.

One good thing about these drugs is that because they're pills, they can be taken at home, unlike some current therapies that require an infusion.

Because Pfizer's pill isn't affected by changes in the spike protein, Dolsten says he expects the new drug will work equally well against any variant of the coronavirus, including omicron.

Although Pfizer has not yet published details of its study, researchers seem impressed.

"I think this drug along with the drug from Merck are both very promising antivirals that, as we had predicted early in this pandemic, work when given early in the infectious course," says Stanley Perlman, a microbiologist at the University of Iowa, where he's been working on coronaviruses for decades.

Perlman adds that the key to preventing damage from a coronavirus infection is to stop it from replicating and spreading throughout someone's body.

Protease isn't the only viral protein that might lead to a viable treatment.

"I think there's several other targets in how the virus reproduces," Perlman says. "But the most important thing to think about for all of them is they almost all have to be given very early after infection to really have a role in helping prevent people from progressing to more severe disease."

And since it looks like we'll be living with COVID-19 for a while, drugmakers have an incentive to develop other kinds of drugs to treat the disease.

Copyright 2021 NPR. To see more, visit https://www.npr.org.