Scientists at Pfizer’s research and development lab in Groton, Conn., studied a COVID-19 pill called Paxlovid.
Stew Milne / AP
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Stew Milne / AP
Scientists at Pfizer’s research and development lab in Groton, Conn., studied a COVID-19 pill called Paxlovid.
Stew Milne / AP
Two new drugs are awaiting approval from the Food and Drug Administration to treat patients with COVID-19 and both may be effective against the omicron variant.
One is made by Merck, the other by Pfizer.
NS Drugs Merck has been developed for many years. When the pandemic started, Pfizer’s drug didn’t exist. Its development story is another example of how COVID-19 has accelerated drug and vaccine development.
Pfizer does not start from exactly zero. Mikael Dolsten, Pfizer’s chief scientific officer, said during the 2003 SARS outbreak, the company’s scientists began looking for ways to combat that coronavirus.
In particular, they look for proteins important for the virus to replicate after it infects someone.
Pfizer focuses on viral protein needs to replicate
One viral protein they focus on is called a protease. “We learned that protease is a key regulator for viruses to release machinery and hijack human cells,” said Dolsten.
The Pfizer scientists thought that if they could find a compound that could disrupt the protease, it would essentially stop the virus from dying on its tracks.
That search ended when the 2003 SARS outbreak passed. There is no disease, no market for a drug.
But Dolsten said the knowledge gained convinced them that a protease inhibitor would work to kill the coronavirus that causes COVID-19.
They created computer models of the viral protease protein and assembled drug candidates that could block it.
“We really had to design and synthesize about 600 unique chemical compounds,” he said.
Old medicine makes new medicine work better
That was just the beginning. They had to test each compound to see how well it stopped the virus from infecting cells in the lab. They then had to determine if it did the same thing in animals infected with the coronavirus. They also need to find a candidate that can stay in a person’s body long enough to have the desired antiviral effect. And they want to do all this fast.
“We’ve come up with some very aggressive timelines that we’ve done all of this over four months to deliver the optimal drug,” says Dolsten.
Finally, drug developers had a candidate they thought would work. They mixed it in a pill with an older drug called ritonavir to extend the protease inhibitor’s activity.
This past July, Pfizer began a study of people infected with the coronavirus at high risk of developing severe COVID. Half took the drug, called Paxlovid, within three to five days of the onset of symptoms, half took a placebo.
Dolsten said that the study was halted early because the drugs seem to be working. He said there was a nearly 90% reduction in hospital admissions in people taking the new drug, “And 100% protection from death.”
A similar analysis for Merck found it reduced the risk of hospitalization or death by 50%. In one Subsequent analysis presented to FDAHowever, the risk reduction is reduced to 30%.
One good thing about these medications is that because they are pills, they can be taken at home, unlike some current therapies that require infusions.
Because Pfizer’s pill is not affected by changes in the mutant protein, Dolsten said he expects the new drug to work equally well against any variant of the coronavirus, including omicrons.
Although Pfizer has yet to release details of its study, the researchers sound impressed.
“I think this drug, along with Merck’s, are both very promising antivirals that, as we predicted early on in this pandemic, will work when given early in the infection,” he said. ,” Stanley Perlman, a microbiologist at the University of Iowa, where he has studied coronaviruses for decades.
Perlman adds that the key to preventing damage from a coronavirus infection is to prevent it from replicating and spreading throughout someone’s body.
Protease isn’t the only viral protein that could lead to a possible treatment.
“I think there are some other goals in how viruses reproduce,” says Perlman. “But the most important thing to think about for all of them is that almost all of them have to be vaccinated very soon after infection to really play a role in helping to 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 drugs to treat the disease.
