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COVID-19 pills for at-home use are likely to arrive soon, but they come with drawbacks

The treatments will require a strict, time-sensitive dosing protocol that includes taking as many as 40 doses in 5 days.

Pfizer's COVID-19 pill.thomas hansmann.fotograf/Associated Press

The first prescription pills to treat COVID-19 at home are expected to become available within weeks and will likely work against the worrisome Omicron variant, infectious disease specialists say, but they warn that the drugs come with significant drawbacks and shouldn’t be considered a substitute for vaccines.

Patients will need to start taking the pills within five days of the onset of symptoms ― which means getting a COVID test, diagnosis, and prescription quickly ― and must swallow 30 to 40 pills over five days. Those requirements could limit use of the medicines.

“As a clinician seeing patients, I want more tools in my toolbox,” said Dr. Lindsey Baden, an infectious disease expert at Brigham and Women’s Hospital who chaired an independent panel of scientists that recently narrowly recommended that the Food and Drug Administration authorize the first drug for emergency use. The new potential treatments would help prevent early COVID cases from progressing, Baden said, “but they are incremental ― they are not a panacea.”

The first of the pills, called molnupiravir, is an antiviral medication made by Merck and Ridgeback Biotherapeutics. An FDA advisory panel voted 13-10 on Nov. 30 to endorse its use. Baden voted with the majority, but opponents said they were unsure whether the drug’s benefits outweighed its risks.

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Molnupiravir reduced the risk of hospitalization and death by 30 percent when taken within five days of symptom onset in a trial of unvaccinated patients with at least one risk factor for severe disease, in comparison with a placebo. That marked a significant decline from an earlier analysis by Merck that indicated the drug lowered the risk by 50 percent.

The US government has paid about $2.2 billion for roughly 3.1 million courses of the treatment, each of which requires patients to take 40 doses. The FDA is expected to clear molnupiravir any day, although an agency spokeswoman declined to give a timetable this week.

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A second antiviral regimen, developed by Pfizer, may work better. An interim analysis of a clinical trial indicated that the drug, called Paxlovid, was 89 percent effective when taken within five days of the start of symptoms. Pfizer CEO Albert Bourla said on CNBC on Wednesday that within days his company will submit updated data to the FDA that show no reduction in efficacy.

Pfizer has reached a deal with the federal government to provide up to 10 million courses of Paxlovid for $5.3 billion. Each course requires 30 pills that include an experimental compound and an HIV drug as a booster. The FDA advisory committee is expected to weigh in on Pfizer’s treatment, as it did with the one from Merck. On CNBC, Bourla predicted the agency will render a decision this month.

Currently, the only authorized treatments for nonhospitalized COVID patients are monoclonal antibodies, which are laboratory-produced molecules that act as substitute antibodies that can restore, enhance, or mimic the immune system.

Those drugs, whose makers include Regeneron Pharmaceuticals and Eli Lilly, also must be given soon after symptoms appear, but they have several other drawbacks. The medicines typically require a closely monitored hourlong intravenous infusion in a clinical setting when patients are at their most contagious, and staff must wear full protective gear. And Regeneron said early studies indicate its treatment is less effective against Omicron.

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GlaxoSmithKline and Vir Biotechnology have collaborated on another intravenous monoclonal antibody that the firms recently said worked well against Omicron in laboratory studies.

Given the challenges involved with administering monoclonal antibodies, only about 60 patients in the Mass General Brigham health care system, the state’s largest, receive the treatment each day, according to Dr. Paul Sax, another infectious disease specialist at Brigham and Women’s. He said roughly three to four times as many patients in the network would benefit from the antibody treatment each day, but most can’t get it.

“The United States health care system is not really set up to deliver intravenous infusions outside the hospital,” said Sax. “Various strategies have been started to make it easier to do, but it’s still not easy.”

In contrast, patients who are prescribed antivirals could take the pills at home. They also work differently from monoclonal antibodies.

Molnupiravir stops the genetic material in SARS-CoV-2, the virus that causes COVID-19, from replicating itself accurately. It inserts mutations that get replicated over and over, ultimately killing the virus. Paxlovid, the Pfizer drug, has a different mechanism and combines an experimental compound with an HIV treatment called ritonavir.

Scientists expect that both drugs will work against Omicron. The variant has at least 30 mutations on the spike protein, which the virus uses to invade cells. Experts believe the extraordinary high number of mutations is likely to blunt the effectiveness of the three US vaccines that target that part of the virus. (Pfizer and its German partner BioNTech said Wednesday that the booster dose of their vaccine may neutralize the variant.) Neither the Merck nor the Pfizer antiviral drugs target the spike protein and should not be affected by the mutations, although the companies plan to confirm that in studies.

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Because molnupiravir works by introducing mutations in the virus, several members of the FDA advisory committee were concerned that it could do the same in human cells, in particular in the fetuses of pregnant women. The FDA is considering a blanket restriction on use by pregnant women, or only allowing doctors to prescribe the drug to pregnant women in rare cases when they are diagnosed with COVID and are at high risk of getting seriously sick. (Paxlovid doesn’t introduce mutations so it isn’t expected to raise the same issues.)

One committee member, Dr. Sankar Swaminathan, chief of infectious diseases at the University of Utah School of Medicine, said he also worried that the drug might affect the DNA of other cells in men and women, not just those of fetuses.

“There were too many unanswered questions and not enough data to firmly say the benefits outweighed the risks,” said Swaminathan, who voted not to recommend the Merck drug. He added that the efficacy of the medication “is not overwhelming.”

Other medical experts are worried that antiviral drugs may not get into the mouths of the US patients who have often been hit hardest by COVID, those with limited access to health care.

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Dr. Adam Gaffney, a pulmonary and critical care physician at Cambridge Health Alliance and assistant professor at Harvard Medical School who is not on the FDA advisory panel, said recipients will need to recognize COVID symptoms, get tested for the virus, receive the results, visit a physician, and get a prescription ― all within five days.

“We know it’s not enough for a medication to exist,” said Gaffney, who wants the government to make COVID tests more widely available and supports national health insurance. “People need to have access to the health care system in order for that medication to work.”

Several infectious disease experts also said that with only 60 percent of the US population fully vaccinated ― and parts of the world such as Africa having less than 7 percent of residents fully vaccinated ― the most powerful weapon against COVID remains broader use of vaccines.

“We’re not going to treat our way out of this pandemic,” said Swaminathan, the FDA advisory panel member. “To get back to normal, we have to get closer to herd immunity, and right now the only way to do that is through more vaccinations.”

Nonetheless, other members of the advisory committee said they welcome the arrival of the antiviral drugs, even with the caveats.

“I look upon this as only the first generation” of such pills, said Dr. W. David Hardy of Charles Drew University School of Medicine and Science in Los Angeles, who voted to recommend the Merck drug. “We’ve had reports that there are better drugs coming down the pike that are also oral. . . . In the environment that we’re in, having additional medications, even if they’re not fantastic, is helpful.”


Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.