Jeremy Faust delivers a counterintuitive and deeply humanizing analysis of recent clinical trials, arguing that the failure of Paxlovid to prevent hospitalizations is not a medical defeat, but a historic victory for public health. While headlines might scream "drug failure," Faust reframes the data to reveal a world where the virus itself has been tamed by immunity, rendering the once-critical medication largely obsolete for the general population. This is a story not about a drug losing its power, but about humanity winning the war against the virus's lethality.
The Real Lede: Zero Deaths
The most striking element of Faust's piece is his refusal to treat the negative trial results as a disappointment. Instead, he zeroes in on the most profound statistic: in two massive randomized controlled trials involving over 4,000 high-risk adults, there were no deaths from any cause, regardless of whether the patients received the antiviral or standard care. "Zero deaths from any cause in the study, regardless of which group the patients were in," Faust writes, noting that the realization made the hair on his arms stand up. He argues that this outcome is the true headline, suggesting that the baseline risk of death has plummeted so low that even a highly effective drug cannot statistically demonstrate a further reduction.
This framing is powerful because it shifts the metric of success from "did the drug work?" to "how safe is our world now?" By contrasting the current 0.77% hospitalization rate with the 6.53% rate seen in the 2022 EPIC-HR study, Faust illustrates that time and immunity have done more to reduce risk than the medication ever could. He notes that in the earlier study, one in fifteen people faced severe outcomes, whereas now, only one in 130 does. "Time does not need to be prescribed. And it's free," he observes, a line that elegantly captures the shift from a crisis of scarcity to a reality of abundance in public health safety.
"We're simply living in a better world than the one where Paxlovid was life-saving."
The Paradox of Success
Faust tackles the psychological difficulty of accepting this news. He acknowledges that many experts and patients are clinging to the drug's utility, engaging in what he describes as "Five Stages of Grief-type bargaining." He dismantles four common arguments used to defend Paxlovid's continued widespread use. First, he addresses the claim that the drug improves symptoms, pointing out that the recent trials were unblinded, likely inflating the perceived benefit through the placebo effect. He contrasts this with the blinded EPIC-SR study, which found no difference in symptoms, stating, "You abide by the better one—in this case the one with blinding and a placebo."
Second, he refutes the idea that the new trials were "underpowered," reminding readers that the study was actually 50% larger than the original pivotal trial. Even if the study were expanded to 50,000 people to find a tiny statistical benefit, Faust argues the cost-benefit ratio would be absurdly high. "The fraction of patients benefiting would be so small, that it would cost many hundreds of thousands of dollars worth of Paxlovid to save a single hospitalization," he writes. This economic reality check is crucial for policymakers who must allocate limited resources.
Critics might argue that dismissing the drug entirely ignores the nuances of individual patient needs, particularly for those with complex comorbidities not fully captured in aggregate data. However, Faust counters that even among the immunocompromised—the group most likely to benefit—the hospitalization rate was so low (1%) that the drug showed no statistical advantage over standard care. "If you'd told me last year that PANORAMIC would show such a low hospitalization rate in immunocompromised patients with Covid-19, I'd have been dancing on the rooftops," he admits, highlighting that the success of the immune system, not the drug, is the primary driver of survival.
The Long Shadow of Rebound and Delay
The commentary also turns a critical eye toward the pharmaceutical landscape and the lingering risks of the drug. Faust warns that in the absence of significant benefits, the downsides of Paxlovid—such as side effects and the phenomenon of "rebound," where symptoms return after initial improvement—become the dominant considerations. He notes that while longer courses might reduce rebound, the data remains uncertain. "I'm reasonably convinced that Paxlovid causes rebound far more often than Pfizer initially acknowledged," he states, adding a layer of caution to the drug's legacy.
Perhaps the most unsettling part of the analysis is the timeline. Faust uncovers a "billion-dollar delay," revealing that the data for these trials was collected over two years ago, yet the publication was delayed until recently. He traces the manuscript's journey, noting it was submitted to the New England Journal of Medicine in early 2025 and sat in revision for a year. "What on Earth took a year after that?" he asks, pointing to a pulled preprint and a lack of transparency from the publisher. This delay, he suggests, allowed the drug to continue being sold and prescribed on outdated assumptions long after the evidence had shifted.
"Clinging to Paxlovid is less scientific than nostalgic."
This observation cuts to the heart of the article's emotional core. Faust suggests that the attachment to the drug is a relic of a darker time when we desperately needed a miracle. He draws a parallel to the concept of herd immunity, reminding readers that the collective safety we enjoy now is the result of billions of individual immune responses, a phenomenon that has rendered the acute-phase antiviral less critical than it was during the early waves of the pandemic.
Bottom Line
Jeremy Faust's analysis is a masterclass in reframing negative data as a positive societal outcome, proving that the best news in medicine is sometimes the news that a drug is no longer needed. While his dismissal of Paxlovid's utility for the general population is robustly supported by the data, the article leaves a lingering question about the transparency of the publication process and the specific protocols for the most vulnerable immunocompromised patients. The strongest takeaway is not just that the virus is less deadly, but that our definition of medical necessity must evolve as the threat landscape changes.