Late stage study results have finally been released for Pfizer's Paxlovid, the anti-viral pill designed by the pharmaceutical giant to protect against severe COVID and death. And the results showed that the drug might be more effective than Pfizer's industry-standard vaccine at protecting against the severe illness and death caused by COVID.
The number to keep in mind: the drug reduced hospitalization and death by 89% in high-risk patients, if taken within three days of symptom onset.
That's how effective the pill is at reducing both hospitalizations and deaths in adult patients at high risk of severe infection.
The positive results were released at a critical time: the FDA is reviewing whether to clear the use of Paxlovid in high-risk adults. And researchers are happy with the data, with some senior Pfizer execs calling it a home run.
"This was a real home run, gives tremendous hope for another highly effective intervention," said Pfizer Chief Scientific Officer Mikael Dolsten in an interview.
In addition to making dramatic inroads for patients who are at high risk, the preliminary analysis showed the drug may also help people at low risk of severe COVID - for example, vaccinated patients who fall victim to a breakthrough infection - avoid becoming seriously ill. The data showed the drug reduced risk of hospitalization by 70%, although it failed to reduce or resolve symptoms within three or four days, suggesting it will be of limited use for patients only suffering from mild symptoms.
The study criteria showed patients who were at high risk of developing severe disease had to have at least one underlying health condition, like being obese or elderly. The other study included people who were either unvaccinated and at low risk, or who were young and healthy individuals, or vaccinated people with at least one risk factor for developing severe disease.
In the final analysis, five of the 697 high-risk subjects who participated in the study received the drug within three days of symptom onset and were hospitalized or died from COVID, compared with 44 out of 682 subjects who received a placebo. Nine study volunteers who received a placebo died, compared with none in the treatment arm, the company said.
Meanwhile, researchers also reported that the drug was 88% effective if taken within five days of symptoms. Two of the 333 low-risk subjects who got Paxlovid were hospitalized, however, compared with eight of 329 subjects who received a placebo, resulting in the 70% efficacy.
Both studies testing Paxlovid in actual patients showed that the viral load seen in subjects who received the drug was significantly lower than in the placebo groups.
Doctors and health experts have been looking for an antiviral like Paxlovid, which people could easily take at home within several days of symptoms emerging to prevent their cases from turning serious and requiring hospitalization.
As for whether the pill will protect patients from the omicron variant, researchers suspected Pfizer’s pill would hold up well because it stops the virus by blocking the activity of a key enzyme, known as protease, that the virus needs to replicate.
"Without the protease functioning, the virus can’t replicate and cause disease," Dr. Dolsten said in an interview. "I’m very convinced that the effects on Omicron by Paxlovid will be very substantial."
This enzyme isn't believed to have mutated in the omicron variant. Early Pfizer lab tests showed that Paxlovid blocked the protease enzyme in omicron, as well as other variants of concern, like delta and beta.
It's likely the FDA will approve the drug for use on high-risk patients in the coming weeks, likely before the end of the year.
Readers can find the full press release below:
Pfizer today announced final results from an analysis of all 2,246 adults enrolled in its Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) trial of its novel COVID-19 oral antiviral candidate PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets). These results were consistent with the interim analysis announced in November 2021, showing PAXLOVID significantly reduced the risk of hospitalization or death for any cause by 89% compared to placebo in non-hospitalized, high-risk adult patients with COVID-19 treated within three days of symptom onset. In a secondary endpoint, PAXLOVID reduced the risk of hospitalization or death for any cause by 88% compared to placebo in patients treated within five days of symptom onset, an increase from the 85% observed in the interim analysis. The EPIC-HR data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission for Emergency Use Authorization (EUA).
“This news provides further corroboration that our oral antiviral candidate, if authorized or approved, could have a meaningful impact on the lives of many, as the data further support the efficacy of PAXLOVID in reducing hospitalization and death and show a substantial decrease in viral load. This underscores the treatment candidate’s potential to save the lives of patients around the world,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “Emerging variants of concern, like Omicron, have exacerbated the need for accessible treatment options for those who contract the virus, and we are confident that, if authorized or approved, this potential treatment could be a critical tool to help quell the pandemic.”
EPIC-HR Final Results
In the final analysis of the primary endpoint from all patients enrolled in EPIC-HR, an 89% reduction in COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset was observed, consistent with the interim analysis. In addition, a consistent safety profile was observed.
0.7% of patients who received PAXLOVID were hospitalized through Day 28 following randomization (5/697 hospitalized with no deaths), compared to 6.5% of patients who received placebo and were hospitalized or died (44/682 hospitalized with 9 subsequent deaths). The statistical significance of these results was high (p<0.0001). In a secondary endpoint, PAXLOVID reduced the risk of hospitalization or death for any cause by 88% compared to placebo in patients treated within five days of symptom onset; 0.8% of patients who received PAXLOVID were hospitalized or died through Day 28 following randomization (8/1039 hospitalized with no deaths), compared to 6.3% of patients who received placebo (66/1046 hospitalized with 12 subsequent deaths), with high statistical significance (p<0.0001). Relative risk reduction was 94% in patients 65 years of age or older, one of the populations at highest risk for hospitalization or death; 1.1% of patients who received PAXLOVID were hospitalized through Day 28 (1/94 hospitalized with no deaths), compared to 16.3% of patients who received placebo (16/98 hospitalized with 6 deaths), with high statistical significance (p<0.0001). In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID as compared to 12 (1.2%) deaths in patients who received placebo.
In the EPIC-HR trial, in a secondary endpoint, SARS-CoV-2 viral load at baseline and Day 5 have been evaluated for 499 patients. After accounting for baseline viral load, geographic region, and serology status, PAXLOVID reduced viral load by approximately 10-fold, or 0.93 log10 copies/mL, relative to placebo, indicating robust activity against SARS-CoV-2 and representing the strongest viral load reduction reported to date for an oral COVID-19 agent.
Treatment-emergent adverse events were comparable between PAXLOVID (23%) and placebo (24%), most of which were mild in intensity. Fewer serious adverse events (1.6% vs. 6.6%) and discontinuation of study drug due to adverse events (2.1% vs. 4.2%) were observed in patients dosed with PAXLOVID, compared to placebo, respectively.
All other secondary endpoints for this study, which are available on clinicaltrials.gov (NCT04960202), were not yet available for this review. Full study data are expected to be released later this month and submitted to a peer-reviewed publication.
EPIC-SR Interim Results
Interim analyses of the EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) Phase 2/3 study, which included unvaccinated adults who were at standard risk (i.e., low risk of hospitalization or death) as well as vaccinated adults who had one or more risk factors for progressing to severe illness, showed that the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo, was not met.
The key secondary endpoint showed a 70% reduction in hospitalization and no deaths in the treated population for any cause compared to placebo. Additionally, there was approximately a 10-fold, or 1 log10 copies/mL, decrease in viral load compared to placebo, consistent with results from the Phase 2/3 EPIC-HR study.
The data were reviewed by an independent Data Monitoring Committee (DMC) and, based on the totality of the data available, the DMC recommended that the trial continue.
At the EPIC-SR interim analysis, which included 45% of the trial’s planned enrollment, 0.6% of those who received PAXLOVID were hospitalized following randomization (2/333 hospitalized with no deaths), compared to 2.4% of patients who received placebo and were hospitalized or died (8/329 hospitalized with no deaths). A follow-on analysis at 80% of enrolled patients was consistent with these findings. In this analysis, 0.7% of those who received PAXLOVID were hospitalized following randomization (3/428 hospitalized with no deaths), compared to 2.4% of patients who received placebo and were hospitalized or died (10/426 hospitalized with no deaths); p=0.051.
Treatment-emergent adverse events were comparable between PAXLOVID (22%) and placebo (21%), most of which were mild in intensity. Rates of serious adverse events (1.4% vs. 1.9%) and discontinuation of study drug due to adverse events (2.1% vs. 1.2%) were also comparable between PAXLOVID and placebo.
All other secondary endpoints for this study, which are available on clinicaltrials.gov (NCT05011513), were not yet available for this review. The study is now fully enrolled, and further data will be released upon analysis of the full study data expected later this month.
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