Scientists Say a COVID-19 Pill Is Coming Soon, Up for FDA Review

You have limited options right now if you know you’ve been exposed to COVID-19. There used to be monoclonal antibody treatments available, but those were given through an IV, and the Food and Drug Administration (FDA) has since revoked their authorization. Nirmatrelvir–ritonavir (Paxlovid) has also been used in the past to prevent COVID-19 after exposure, but more recent data suggests it isn’t particularly effective when used this way.

But that could be about to change. Now, new research published in the New England Journal of Medicine suggests that a pill to help prevent COVID-19 may be in your future.

Meet the experts: William Schaffner, M.D., an infectious disease specialist and professor at the Vanderbilt University School of Medicine; Amesh A. Adalja, M.D., a senior scholar at the Johns Hopkins Center for Health Security; Paul E. Sax, M.D., study co-author and clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School.

The double-blind, randomized, placebo-controlled trial included 2,041 participants, whom the researchers split into an experimental and a control group. One group was given the new COVID-19 pill, an oral medication called ensitrelvir, for five days, while the other group received a placebo. Both treatments were administered to the participants within 72 hours of their exposure to someone with COVID-19.

The researchers discovered that people who took ensitrelvir after being exposed to the virus were significantly less likely to develop COVID-19 compared to those who took a placebo. The trend held even for participants who were at a higher risk for severe COVID-19.

Infectious disease doctors say this is a welcome tool in preventing the spread of COVID-19. Here’s why.

Ensitrelvir (Xocova) is an oral antiviral medication that blocks the main protease of SARS-CoV-2, the virus that causes COVID-19. (A protease is necessary for a virus to replicate and infect other cells.)

Ensitrelvir specifically blocks the 3CL protease on SARS-CoV-2 and keeps it from replicating. As a result, it can potentially keep someone from getting sick or shorten the intensity and amount of time they have symptoms.

The study found that taking 375 milligrams of ensitrelvir on day one and 125 milligrams of the medication on days two through five was most effective in preventing people who had been exposed to COVID-19 from getting sick.

Specifically, the researchers observed that people who took ensitrelvir after being exposed to the virus were 67% less likely to develop COVID-19 compared to those who took a placebo. For participants who were at a higher risk for severe COVID-19, the odds of developing the virus dropped by 76%.

Based on the preliminary data, the COVID-19 pill may be more effective at preventing the virus than the current COVID-19 vaccine (data on the effectiveness of the COVID-19 vaccine at preventing infection suggests the shot is nearly 45% at preventing infection right after you get it, before dropping to 16.7% effectiveness after 20 weeks). However, the vaccines still offer greater protection against severe illness and hospitalization.

It’s important to note that not everyone in the placebo group got sick after being exposed to COVID-19. The data found that 2.9% of people in the ensitrelvir group contracted the virus after exposure, while 9% of those in the placebo group got sick.

Side effects were reported by 15.1% of people in the ensitrelvir group and 15.5% of people in the placebo group—so, they were about equal. These were the most common side effects reported in both groups:

• Headache
• Diarrhea
• Common cold
• Cough
• Fatigue
• Flu

People in the placebo group had the same side effects and at similar levels to those who took ensitrelvir, making it hard to say how likely these side effects are when you take the medication.

“Right now, there is no easily administered post-exposure prophylaxis available for household contacts of COVID,” says Paul E. Sax, M.D., study co-author and clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School. “Even though the severity of COVID has declined since the beginning of the pandemic, the disease still can cause severe illness.”

Doctors are excited about the data. “It’s wonderful to have another preventative modality available to people who are exposed to COVID, particularly those in high-risk circumstances,” says William Schaffner, M.D., an infectious disease specialist and professor at the Vanderbilt University School of Medicine.

Amesh A. Adalja, M.D., a senior scholar at the Johns Hopkins Center for Health Security, agrees. “These are powerful findings that prove the value of ensitrelvir in this context,” he says.

Dr. Schaffner praises the high potential for accessibility in people who want to lower their risk of getting COVID-19 after an exposure. “It ought to be easy to get,” he says. “It ought to be available through every pharmacy.”

While previous treatments to prevent a COVID-19 infection after exposure have mostly been limited to high-risk groups, Dr. Adalja says it’s “conceivable” that ensitrelvir would be available to anyone who has been exposed and wants to avoid getting sick. He calls ensitrelvir a “simple way” to prevent COVID-19 after an exposure.

Doctors say we can’t go that far just yet. “Nearly 100% of the participants in the study had evidence of prior immunity to COVID, and most of them had been vaccinated,” Dr. Sax says. “Nonetheless, treatment reduced the risk of acquiring COVID by 67% even in this population. This suggests that ensitrelvir preventive therapy is complementary to vaccination rather than replacing it.”

Instead, Dr. Adalja recommends thinking of ensitrelvir as an “important complement” to the COVID-19 vaccine.

Dr. Schaffner agrees that the COVID-19 vaccine is still the best way to prevent people from getting sick. “The vaccine continues to be the foundation of prevention,” he says.

Ensitrelvir is not yet available in the U.S., though it is currently approved for use in Japan. The drug is currently under FDA review, and a decision is expected as early as next month. If it’s approved, ensitrelvir will be the only medicine used to prevent COVID-19 after you’ve been exposed.

Infectious disease experts stress that you shouldn’t stop getting your annual COVID boosters just yet. You won’t be seeing ensitrelvir on pharmacy shelves for at least another month, and that’s assuming it gets FDA approval. Still, there’s reason to believe that an effective COVID-19 pill isn’t far off. “We’re really delighted about this,” Dr. Schaffner says. “Many of us have heard that this was in the works. It’s very welcome.”