The Path to Paxlovid

Although COVID-19 cases around the world have declined in recent months, that trend has been upended by the highly contagious BA.2 Omicron variant. Paxlovid, Pfizer’s oral COVID-19 treatment, could be a lifeline for those at high risk of serious disease. The antiviral showed tremendous promise in clinical trials: compared with a placebo, it reduced the risk of hospitalization or death from COVID-19 by 88% if given within 5 days of the onset of symptoms. Based on that data, the U.S. Food and Drug Administration gave Paxlovid emergency use authorization in December, and the federal government ordered enough of the antiviral to treat 20 million people through 2022. Pfizer announced that it plans to make 120 million courses of treatment this year and will seek full regulatory approval for the antiviral. Paxlovid’s existence is remarkable, considering that its antiviral ingredientoriginally called PF-07321332 and recently dubbed nirmatrelvirwas not even a sketch in a medicinal chemist’s lab notebook 2 years ago. The antiviral went from an idea to the first clinical test in a person in 12 monthsa breathtaking pace at which to deliver a bespoke drug candidate. The drug discovery story began Friday, March 13, 2020, when medicinal chemist Dafydd Owen was sent home from his job at Pfizer in Cambridge, Massachusetts. Like many employers at the time, the pharmaceutical giant was halting most on-site operations in the face of the national emergency over COVID-19. Owen’s bosses asked him to spend the weekend thinking about what resources he would need to lead a program to develop an oral drug to fight the emerging pandemic. It was an unusual choice in some ways: Owen had never worked on an antiviral and had never been a project leader. Owen has spent his entire career at Pfizer. He started working at the company’s Sandwich, England, site in 1999 and moved to the U.S. in 2011. For the past decade, he says, his role has been to help pick targets for medicinal chemistry programs. He’s helped kick off campaigns in oncology, pain management, and cardiovascular disease. “I wanted to start the right programs, which I think is a critical part of a good decision-making at big pharma companies,” he says. But Owen says he was happy to take on leadership of the oral antiviral program. His status as a rookie project leader may have given him an advantage. “We were all sent home on that Friday, and the world was completely different,” he