This strategy was a long way off, but success would have led to taking antiviral pills more quickly than trying to make an entirely new drug. What followed was a brutal wave of failures. Antiviral drugs that worked in petri dishes failed when tested on animals, and those that worked in animals failed in clinical trials.
Even drugs that have gone into clinical trials have often been disappointing. A flu drug called favipiravir provided promising results in early trials, prompting Canada-based Appili Therapeutics to start a late-stage trial 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 the research is a huge success,” said Dr. Fauci.
Merck’s new drug, molnopiravir, was studied in 2019 by a nonprofit company associated with Emory University as a treatment for Venezuelan equine encephalitis virus — an unknown pathogen feared as a potential biological weapon. When molnopiravir encounters the virus’s genes, it wreaks havoc, resulting in a group of new mutations. New viruses are often left unable to reproduce.
In October, Merck announced the preliminary results of its trial of molnupiravir: The drug reduced the risk of hospitalization and death by about 50 percent. Eager to curb the toll of the Covid-19 virus, the US government has purchased nearly 3.1 million cycles of molnopiravir for $2.2 billion.
But in the final analysis of the trial, the drug’s effectiveness fell to 30 percent. At the November 30 meeting of the Food and Drug Administration’s Advisory Committee, experts discussed the potential for the drug to cause mutations not only in viruses, but in people’s DNA. The committee voted to recommend licensing Molnopiravir, but by a narrow majority. And even panelists who voted for the drug expressed strong reservations, given the potential side effects.
Now, Pfizer’s drug is next to enter the spotlight. Its origins go back nearly two decades, when Pfizer researchers were searching for a drug that could fight the coronavirus that causes SARS. They decided to build a molecule that could block an essential viral protein known as a protease. The protease acts like molecular scissors, cutting long molecules into pieces that help make new viruses.
The drug, originally called PF-00835231, settled in proteases like a piece of gum sandwiched between the scissors’ blades. PF-00835231 has been shown to be effective against SARS when administered intravenously to mice.