The EPIC-HR trial, conducted early in the COVID-19 pandemic, demonstrated that oral nirmatrelvir-ritonavir (NMV/r) is over 85% effective in preventing hospitalization and death among unvaccinated high-risk patients, raising questions about its relevance in today’s context of high population-level immunity. Although, the relevance of these findings in the context of current high population-level immunity remains unclear. To address this, investigators evaluated the efficacy of NMV/r (Paxlovid) in a subset of high-risk trial participants with pre-existing SARS-CoV-2 immunity from prior infection or vaccination. This analysis focused on the outcomes associated with Paxlovid in high-risk EPIC-HR and EPIC-SR modified intention-to-treat patients with a history of SARS-CoV-2 infection or vaccination.
John McLaughlin, PhD, epidemiologist, VP, and head of anti-infectives, COVID-19, and flu vaccines at Pfizer provides an overview at last week’s IDWeek this real-world analysis, “One of the questions with Paxlovid in the contemporary era is, how is Paxlovid performing among people who have pre-existing immunity, either from vaccination or prior infection? Because in the original trials, everybody was pretty much unvaccinated, and most people had no evidence of previous infection. The analysis that we did took people from our first study, EPIC-HR, who were baseline seropositive, or people from the EPIC-SR trial who were previously vaccinated, and we still showed that in that population, people with pre-existing immunity, Paxlovid was still providing a benefit against hospitalization and death, severe symptoms, all symptoms. It’s still working, even though the height of the pandemic has come down and more people have baseline immunity.”
A total of 1,600 participants were involved in the study. Among them, 969 were high-risk and had SARS-CoV-2 antibodies, while 631 were high-risk and vaccinated. Of these, 807 received Paxlovid, and 793 received a placebo.
Paxlovid lowered the risk of COVID-19 hospitalization and death by 73.7% compared to placebo. It also reduced medical visits for COVID-19 by 65% and severe symptoms by 22% to 46% in the weeks after treatment. Additionally, those who took Paxlovid experienced symptom relief two days sooner than those on placebo.
McLaughlin discussed the new information this analysis provides about Paxlovid in previously infected or vaccinated patients, “I think the biggest thing that it adds is that there’s still an incremental benefit in today’s world among people with pre-existing immunity to take Paxlovid. If you’re a high-risk patient and you’re eligible for Paxlovid, it’s still providing a benefit against hospitalization and death. We also showed that it reduced severe symptoms and reduced all COVID-19-related medical encounters, so it’s still providing a benefit, even though the absolute rates of disease aren’t the same as we saw early on in the pandemic.”
The effectiveness of Paxlovid administered within 5 days of the onset of COVID-19 symptoms was evaluated against a placebo over 28 days across various pre-defined outcomes. The analysis combined data from two Phase 2/3 randomized controlled trials with modified intention-to-treat populations:
1. High-risk EPIC-HR patients who were unvaccinated and seropositive for SARS-CoV-2 at baseline
2. High-risk EPIC-SR patients who had previously received a COVID-19 vaccine.
According to McLaughlin, clinicians should note, “There’s still a benefit of Paxlovid, and even though we’re not in the height of the pandemic, it’s still providing a benefit for patients. So if you have an eligible patient in front of you who could benefit from Paxlovid and meets the guidelines for Paxlovid, then you should think about offering that drug to them, because it’s still going to reduce their risk of severe outcomes that we know are still occurring from COVID-19.”
In a group of trial participants with existing natural or vaccine-derived immunity to SARS-CoV-2, Paxlovid treatment significantly lowered the risk of COVID-19 hospitalization and death, with a number needed to treat of 71. Patients who received the treatment also had fewer medical visits related to COVID-19, a lower chance of experiencing severe symptoms, and a quicker recovery. These findings highlight the effectiveness of Paxlovid in high-risk patients with prior SARS-CoV-2 immunity.
