According to a recent study, Pfizer’s Paxlovid appeared to be far more effective at reducing deaths and hospitalizations in older adults than younger patients suffering from the Omicron variant of COVID-19.
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In a recent large-scale study, Pfizer’s Paxlovid (nirmatrelvir and ritonavir tablets) appeared to be far more effective at reducing deaths and hospitalizations in older adults than younger patients stricken with the Omicron variant of COVID-19.
Data from the study, published Wednesday in The New England Journal of Medicine, showed that Paxlovid remained a strong treatment option in patients aged 65 years or older. These individuals saw more than a 70% drop in the risk of hospital admission relative to their untreated counterparts. Paxlovid also cut their risk of death by almost 80%. In patients 40 to 64 years of age who received Paxlovid and had previous immunity, the adjusted hazard ratio for hospitalization was 1.13. This was compared with 0.32 in patients 65 and older with the same pre-existing immunity.
The study was led by Dr. Ronen Arbel of the division of community medical services at Clalit Health Services, one of Israel’s state-mandated health service providers. The study did not look at Paxlovid’s safety in Omicron patients.
Drawing from Clalit’s electronic medical records database, Arbel’s team conducted an observational, retrospective cohort analysis of nearly 110,000 patients. Of the sample, around 3,900 were treated with Paxlovid. The study period ran from Jan. 9 to March 31, during which the Omicron variant was predominant in Israel.
Parallels Between Delta and Omicron Studies
In designing the study, the researchers sought to replicate what the EPIC-HR trial did for Paxlovid during the Delta variant surge of COVID-19.
Published in NEJM in April, EPIC-HR was a double-blinded, randomized and placebo-controlled phase II/III trial assessing the potency of Paxlovid in preventing hospitalization and death through 28 days of infection with the Delta variant. It found that Pfizer’s drug was able to cut the risk of progression to severe disease in symptomatic patients by 89%.
Like Arbel’s paper, EPIC-HR detected a notable age effect. Paxlovid treatment was much more beneficial in patients aged 65 years and above, outperforming placebo by nearly 14 percentage points. In younger patients, its relative advantage was about 4 percent.
However, unlike Arbel’s findings, Paxlovid still showed statistically significant protective effects in the older and younger patient subgroups. This discrepancy in Paxlovid’s performance could be attributed to key differences between the virus and the samples of the two studies.
For instance, 78% of patients in the Omicron paper had existing coronavirus immunity stemming from vaccination or a previous infection. Meanwhile, EPIC-HR specifically enrolled patients without such immunity - all participants were unvaccinated and had never before had confirmed COVID-19. In addition, Omicron has been found to be generally less severe than Delta.
“As expected, the observed risk of hospitalization due to COVID-19 in our study (which was conducted during the omicron-predominant period) was substantially lower than that reported in the EPIC-HR trial during the delta wave,” the study authors wrote.
Paxlovid is a combination of two drugs: nirmatrelvir, which exerts a strong antiviral effect on the coronavirus, and ritonavir, which slows down the liver’s detoxification of nirmatrelvir so that it can work in the body for much longer.
Despite this mechanism of action, there have been reported cases of patients testing positive again after Paxlovid treatment. It is still unknown why these rebounds happen, but a preprint study found signals that underlying medical conditions could potentially aggravate the risk of rebound. This study is still awaiting peer review.
While rebound infections are likely to be rare, the FDA instructed Pfizer this week to conduct an assessment of a second Paxlovid course. In response, the company noted it is working actively with the regulatory agency and expects to finalize the trial’s protocol this month. The FDA expects initial data by Sept. 2023.
