Opinion: Does Paxlovid help people who have been vaccinated against Covid-19? Show us the data!

As a primary care doctor in New York City, I am grateful to drug companies for providing effective Covid-19 therapies for my patients. But I am also frustrated that these companies appear to be completely running the show, and believe that Americans could get more from Big Pharma if only our regulators dared to ask for it. This dynamic is on display with Paxlovid, which was approved based on a study that seems designed to exaggerate the benefit most Americans can expect from this drug rather than provide us with relevant information about it.

Among antiviral agents for Covid-19, Pfizer’s Paxlovid has emerged as the clear winner for two reasons: First, as a pill, Paxlovid is easy to administer, compared to the infusions required for monoclonal antibodies and remdesivir. Second, Paxlovid appears to be highly effective, with a clinical trial showing an 89% relative reduction in hospitalizations or death among high-risk patients who receive it.

I say “appears to be” because there’s a problem: The single trial supporting the FDA’s emergency use authorization of Paxlovid included only unvaccinated people who had never previously had Covid-19. Since 76% of U.S. adults are now vaccinated, and an estimated 58% of Americans have already had Covid, the trial supporting Paxlovid is not directly applicable to a majority of Americans. This means that doctors treating people with the disease don’t know to what degree — if any — Paxlovid will benefit their vaccinated patients. I am left hoping and guessing, and continue to prescribe Paxlovid to my high-risk Covid-19 patients without being sure if I am helping them.

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The current situation with Paxlovid is reminiscent of an older antiviral medication, Tamiflu, which became the subject of controversy during the swine flu pandemic.

Because influenza kills an average of 40,000 Americans a year and hundreds of thousands of people worldwide, efforts have been made to develop antiviral agents that could lessen its severity. Tamiflu (generic name oseltamivir), debuted by Roche in 1999, was purported to be such a medication. Using clinical studies reported by Roche, the available evidence showed that Tamiflu reduced the risk of pneumonia, a common and significant complication of influenza. For years, doctors used Tamiflu under the impression that it reduced the risk of severe disease.

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But during the swine-flu pandemic of 2009, researchers in the United Kingdom and Australia decided to reexamine the evidence supporting the drug. During this process, Keiji Hayashi, a curious pediatrician from Japan, noted that the bulk of the data supporting Tamiflu had never been evaluated by anyone outside of the company that developed it. Governments around the world had been stockpiling Tamiflu to protect their citizens based on its manufacturer saying, “Trust us, it works!”

Cochrane, an international organization dedicated to improving medical knowledge, along with the British Medical Journal instituted a protracted campaign to compel Roche to release its “secret studies” of Tamiflu. After four years, Roche finally provided more complete data to reviewers at Cochrane, who evaluated the information and published an updated assessment that found — you know what’s coming here — there is no evidence that Tamiflu reduces the risk of serious influenza complications, like pneumonia or hospitalization.

Tamiflu enthusiasts will counter that a subsequent reevaluation of the evidence — sponsored by Roche — did show that the medication lowered the risk of influenza-associated pneumonia and hospitalizations. Personally, I am skeptical of a review article paid for by a drug company after a public shaming and in need of reputational rehabilitation.

But despite my doubts about Tamiflu, as a primary care doctor it is hard to ignore a medication that might help my patients, especially one the CDC continues to endorse. So I continue to prescribe Tamiflu to my high-risk influenza patients, hoping I am doing more good than harm.

The situation with Paxlovid isn’t identical to what transpired with Tamiflu, but there’s certainly some historical rhyming: doctors have been left to make clinical decisions about an antiviral medication for a respiratory virus based on inadequate data.

There are two noteworthy facts about the people who were allowed to participate in the Paxlovid trial, all of whom were both unvaccinated and had never previously had Covid-19. First, even when the Paxlovid trial began in July 2021, only a minority of Americans fit into the category of unvaccinated and Covid-naive, so the results of the trial have never been directly applicable to most Americans. Second, Paxlovid would be significantly more effective in people who have not been primed by vaccination or prior infection, so the trial supporting its use serves to exaggerate the benefit that most people would see from the medication.

Yes, Pfizer has begun a trial of Paxlovid in high-risk individuals who have been vaccinated, but this trial combines vaccinated and unvaccinated patients, potentially clouding the issue. More importantly, results of the trial will not be made available until November 2022.

I am not surprised that Pfizer’s first trial was designed to overstate the efficacy of Paxlovid because, as a pharmaceutical company, its goal is to maximize sales. But I am surprised that the federal government would buy $5 billion worth of Paxlovid without requiring that Pfizer move quickly to answer this essential question: How does Paxlovid perform in high-risk people who have been vaccinated or previously infected? A five-day course of Paxlovid costs about $500, but without the appropriate data it’s impossible to tell if this is a good buy or a rip-off.

If, for example, 10,000 courses of Paxlovid must be prescribed to vaccinated people over age 65 to prevent one hospitalization, the country might not move so quickly to replenish its stockpile. Conversely, if ten people taking Paxlovid prevented one hospitalization, the rush would be on to buy more.

Without knowing how Paxlovid performs in vaccinated people, it’s impossible to make these sorts of calculations. Also, given Tamiflu’s history, a demand for data transparency and independent review would be prudent.

Some might suggest I am focusing on a small matter. Who cares if we ultimately learn that the benefits of Paxlovid are greatly attenuated in people who have been vaccinated or previously infected? I raise this issue as being emblematic of a larger problem: a lack of much-needed independent review of pharmaceutical clinical trials.

Americans have seen the scandals that have emerged from lax oversight, like Vioxx being sold despite known cardiovascular risks, or OxyContin contributing to the opioid epidemic. When Covid-19 appeared, the pharmaceutical industry performed exceptionally well, delivering safe and effective vaccines in record time. But long before then, many Americans had learned to distrust Big Pharma, and many have tragically declined this life-saving intervention.

The conversation around vaccine hesitancy has largely focused on misinformation, but what is missing is an acknowledgement that the pharmaceutical industry has spent decades squandering the public’s trust. Doctors have been complicit in this breach by not raising our voices to demand greater transparency and independent review of the pharmaceutical industry. Many doctors have been understandably frustrated with their unvaccinated patients, but we should consider how the medical community has contributed to public distrust of Big Pharma.

Rather than continuing to shake our fists at the unvaccinated, we should look in the mirror and then begin the long work of rebuilding public trust.

Paul Fenyves is a primary care physician at Weill Cornell Medicine in New York, where he is the associate director of digital care and innovation for primary care. He acknowledges help in writing this essay from John Abramson, a faculty member at Harvard Medical School and the author of “Sickening: How Big Pharma Broke American Medicine and How We Can Repair It.”

Source: STAT