This strategy was a long shot, but a success would have led to an antiviral pill faster than trying to create a drug from scratch. What followed was a brutal wave of failure. Antivirals that worked in petri dishes failed in animal testing, and those that worked in animals failed in clinical trials.
Even drugs that made it into clinical trials often proved disappointing. A flu drug called favipiravir showed promising results in early trials, prompting Canada-based Appili Therapeutics to begin late-stage research on more than 1,200 volunteers. But on November 12, the company announced that the pill did not speed recovery from the disease.
“Not everything in research is a great success,” said Dr. Fauci.
Merck’s new drug, molnupiravir, was studied in 2019 by a nonprofit affiliated with Emory University as a treatment for Venezuelan equine encephalitis virus — a little-known pathogen that is feared as a potential bioweapon. When molnupiravir encounters the genes of a virus, it wreaks havoc, leading to a series of new mutations. New viruses are often unable to replicate.
In October, Merck announced the first results of its molnupiravir trial: The drug reduced the risk of hospitalization and death by about 50 percent. The US government, eager to curb the toll of Covid-19, has purchased about 3.1 million courses of molnupiravir for about $2.2 billion.
But in the final analysis of the trial, the drug’s effectiveness dropped to 30 percent. At a Nov. 30 meeting of an FDA advisory committee, experts discussed the potential for the drug to cause mutations not just in viruses, but in people’s own DNA. The committee voted to recommend the approval of molnupiravir, but only by a small majority. And even the committee members who voted in favor of the drug expressed strong reservations, given its potential side effects.
Now Pfizer’s drug is in the spotlight. Its origins date back nearly two decades, when Pfizer researchers were looking for a drug that could fight the coronavirus that caused SARS. They decided to build a molecule that could block an essential viral protein known as a protease. Proteases act like molecular scissors, cutting long molecules into pieces that help build new viruses.
The drug, originally named PF-00835231, stuck in the protease like a piece of chewing gum stuffed between scissors blades. PF-00835231 was shown to be effective against SARS when administered intravenously to rats.
