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Pfizer dominates the COVID drug market. This Watertown biotech wants to change that.

Enanta Pharmaceuticals has started a clinical trial of a pill that it says could be safer than the pharma giant’s Paxlovid.

Watertown-based Enanta Pharmaceuticals is developing a COVID pill that president and chief executive Jay Luly hopes will be an alternative to Pfizer's Paxlovid.Enanta Pharmaceuticals/FayFoto/Boston

A Watertown biotech company has taken a small step forward in its ambitions to give Pfizer’s COVID pill Paxlovid some competition. Enanta Pharmaceuticals told the Globe it has begun an intermediate stage clinical trial of its experimental COVID therapy this week.

Enanta hopes its once-daily pill will be safer to prescribe, easier to take, and potentially more effective than Paxlovid, which is set to earn the pharma giant $22 billion this year. Enanta’s trial is beginning as the third year of the pandemic comes to a close, but president and chief executive Jay Luly says he isn’t worried about being late to the game.


”COVID is not going away,” he said. “We wanted to design something that was better, because we knew we weren’t going to be first.”

Enanta is among a shrinking group of companies still testing experimental COVID pills. The Japanese drugmaker Shionogi and the California firm Pardes Biosciences are testing COVID pills in advanced and intermediate stage trials, respectively. Those could also be direct competitors to Paxlovid. And Boston-based Atea Pharmaceuticals is in the advanced stages of testing a COVID antiviral that could broaden options for doctors and patients.

”We need alternatives to Paxlovid,” said Dr. Melanie Thompson, an HIV physician and clinical researcher at a private practice in Atlanta. “I think these drugs that are in development now will find a market, because we continue to have deaths from COVID and some people still won’t get vaccinated.”

Enanta’s Phase 2 trial ― called SPRINT ― is enrolling about 200 adults with mild or moderate COVID-19 who don’t require hospitalization. Each participant will get Enanta’s pill or a placebo for five days. The company expects to share data from the study in the first half of 2023.

Paxlovid is authorized for treating mild-to-moderate COVID-19 in adults and children ages 12 and up. The drug “has helped keep patients out of the hospital,” said Dr. Kalpana Gupta, chief of staff and chief of infectious disease at VA Boston Healthcare System. But she added that some people can’t take the drug because it can cause harmful interactions when taken with many other drugs, including some blood thinners, seizure medications, and treatments used to prevent abnormal heartbeats.


The culprit behind those safety concerns is an HIV drug called ritonavir, which is one of two compounds in Paxlovid that is included to help slow the metabolism of the second compound, nirmatrelvir, which disrupts the coronavirus’s ability to properly process its genome and curtails its replication.

Doses of the antiviral drug Paxlovid were displayed in New York in August.Stephanie Nano/Associated Press

”There is a very long list of drugs that are tricky to use with Paxlovid,” said Dr. Paul E. Sax, the clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital. “And the people who are at greatest risk for severe developing severe COVID are also the ones with multiple medical comorbidities.”

Enanta’s drug, called EDP-235, targets the coronavirus protease without the need for ritonavir. “Physicians will have to spend much less bandwidth figuring out what to do with a patient,” Luly said.

The Watertown firm’s pill is also designed to be taken once-a-day, instead of twice daily like Paxlovid. And as an added perk, it doesn’t leave a bad taste like Pfizer’s pill, Luly said.

”It seems to have some very positive characteristics,” Thompson said. But the company will ultimately need to do a larger clinical trial to prove its effectiveness, she cautioned.


Enanta will be following patients for four weeks, so it should be able to tell if people have rebound infections — a problem that’s plagued Paxlovid. Earlier studies on Enanta’s drug suggest it is better at reaching the crevices of the body where coronaviruses can hide out, Luly said, which might make it more likely to prevent the rebounds seen with Paxlovid.

Luly said that in contrast to the coronavirus spike protein — which is what most antibodies target — the protease hasn’t changed much across SARS-CoV-2 variants. “And part of the reason for that is the viruses use that enzyme to replicate itself, so it can’t go messing with that too much for its own good,” he said. He expects that Enanta’s drug will continue to be effective for future variants.

Infectious disease doctors are encouraged that companies are still developing COVID drugs that should continue to work even if the virus evades immunity from vaccines.

”COVID antiviral pills still continue to have activity against the current variants, and that’s really fantastic,” Gupta said. “So it makes a lot of sense to be working on something that will continue to be less susceptible to new variants.”

”I think these drugs will be game changers in terms of learning to live with COVID-19 and allow people to resume their normal lives,” she added. “So I am glad to see there are more on the horizon.”

Ryan Cross can be reached at Follow him on Twitter @RLCscienceboss.