Paxlovid, Pfizer’s pill to treat Covid-19, retained its 89% efficacy at preventing hospitalization and death in the full results of a study of 2,246 high-risk patients, the company said Tuesday.
In early November, Pfizer had released interim results from the first 1,219 patients in the study. But another oral antiviral targeting Covid, from Merck and Ridgeback Biotherapeutics, had seen estimates of its efficacy at preventing hospitalization drop from 50% to 30% between an interim result and a final one. A panel of experts advising the Food and Drug Administration on Nov. 30 recommended 13-11 that the Merck pill, molnupiravir, should be authorized for emergency use. The FDA has not announced a decision.
The oral medicines are seen as important because they could be much easier to deliver to infected people than existing drugs like monoclonal antibodies, which must be infused intravenously or injected.
Experts contacted by STAT breathed a sigh of relief that the Pfizer results held up, though all emphasized the need to more fully examine the data, which were shared in a press release, not a scientific publication.
“The protection from hospitalization is obviously fantastic,” said Andrew Pekosz, vice chair of microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health. “That number was a great number. The fact that it was conserved in that final analysis really points to this being a really important weapon in our arsenal to fight Covid-19 particularly as we see more variants that are going to be chipping at that efficacy number.”
Pfizer also reported results from a second study in adults with Covid at normal risk of developing severe disease, a group that included vaccinated people. That study failed to meet its main goal, of increasing the sustained alleviation of self-reported symptoms, at an interim analysis; the study is continuing. But Pfizer said that there was a decrease in hospitalization in that group, too, although numbers were small.
In the study of high-risk patients, called EPIC-HR, 5 of 697 patients who received a five-day course of Paxlovid were hospitalized or died, compared to 44 of 682 who received a placebo. There were no deaths in the Paxlovid group and 9 in the placebo group. Adverse events occurred at similar rates between the placebo and Paxlovid groups, and patients on Paxlovid were less likely to have a severe problem or to stop taking the drug due to a perceived side effect. Patients in the study were considered high risk because they were not vaccinated and had at least one characteristic or underlying medical condition that increased their risk of Covid-19. These could include being over 65, being overweight, or having cardiovascular disease.
The study of patients who were at lower risk, called EPIC-SR, showed that 2 of 333 patients who received a five-day course of Paxlovid were hospitalized compared to 8 of 329 who received placebo. The results were similar in a second analysis, Pfizer said, but barely missed statistical significance. Rates of adverse events were similar between the drug and placebo.
Eric Topol, director and founder of the Scripps Research Translational Institute, said that despite this trial failing to succeed on its main goal of reducing symptoms, he was encouraged by the consistency between the results. “It all fits together,” he said.
Céline Gounder, a clinical assistant professor of medicine and infectious diseases at the NYU Grossman School of Medicine and Bellevue Hospital, said that she was encouraged the efficacy was similar whether the treatment was given within three days of symptom onset or five.
“It means you have a bigger window in order to get a diagnosis and get someone a drug,” Gounder said. “How impactful it will be will be determined by whether people are able to access it in time. The fact that you have a week of business days, that, to me, is really important.”
Paxlovid, if authorized, would be given as two pills of Paxlovid plus one of ritonavir, another antiviral, twice daily for five days. Ritonavir can interact with many other medicines, which could add logistical hurdles for its use.
One big worry, Topol said, was supply of the drug. Pfizer says that it will have 200,000 courses of the medicine available this year and 80 million available next year. But he worried that may not be enough given the waves of Covid that could hit around the world.
Annaliesa Anderson, a Pfizer senior vice president who played a leading role in the treatment’s development, said the company is working to ramp up production, just as it did with the Covid vaccine it developed with BioNTech, looking for ways it can work with partners to speed up production. “We’re doing what we can,” she said.
Anderson said that Pfizer has “great confidence” that Paxlovid will remain potent against the Omicron variant based on in vitro data showing the pill inhibits a key protease enzyme in Omicron. However, she noted, antiviral assays for the new variant have not yet been developed.
She also portrayed the development of the antiviral as, in some ways, bittersweet. Anderson said that a high point in its development had been when Covid vaccines proved effective, and some people asked if an antiviral was necessary. (It was, she said, because vaccines won’t work for everyone and not everyone will have access.) A low point was when other medicines against Covid failed, because she worried that no oral medicines would prove effective.
“We all spent a lot of time developing this antiviral,” she said, “and we hoped we wouldn’t need it.”
Information about how well the study represented people of different backgrounds and ethnicities was not immediately available. Those who were pregnant or breastfeeding were excluded from the trials.
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