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Paxlovid no better than placebo for low risk patients with COVID-19

Paxlovid appears no better than placebo in low-risk patients infected with COVID-19, leading the manufacturer to halt further study recruitment

In a press release from the manufacturer, Pfizer, paxlovid has been found to provide no benefit to patients who are either unvaccinated or vaccinated and who are deemed to be at a low-risk of severe complications such as hospitalisation or death if infected with COVID-19.

Paxlovid is described as a protease inhibitor antiviral treatment for COVID-19 and was designed to be taken orally, at the first sign of infection or once someone first became aware of exposure to an infected individual. It was anticipated therefore that the early use of the drug might help patients avoid severe illness and which might lead to hospitalisation or death, or avoid disease development following contact with an infected individual.

The June 2022 press release follows the success of the results obtained from an earlier trial, EPIC-HR, in which symptomatic, unvaccinated, non-hospitalised adults, at high risk for progression to severe COVID-19, were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelivir plus 100 mg of ritonavir (i.e., Paxlovid) or placebo every 12 hours for 5 days.  The results of EPIC-HR were published in February 2022 and demonstrated that in symptomatic COVID-19 patients, treatment with paxlovid reduced the risk of progression to severe COVID-19 by 89% compared to placebo and without any major safety concerns. Based on these encouraging findings, both the FDA and EMA approved the use of paxlovid for the treatment of mild-to-moderate COVID-19 in adults and children (12 years and older) who were deemed to be at high risk for progression to severe COVID-19, including hospitalisation or death.

With the success of their drug in high-risk patients, Pfizer proceeded with EPIC-SR, a phase 2/3 trial entitled, Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR). This time, the trial was designed to evaluate efficacy and safety in patients with a confirmed diagnosis of COVID-19 infection and who were deemed to be at standard risk (i.e., having a low risk for either hospitalisation or death). Enrolled participants were randomised 1:1, to receive paxlovid or matching placebo orally twice daily for five days.

Paxlovid in low-risk patients

The latest press release provides an updated analysis of the results from the EPIC-SR trial. The trial’s primary endpoint was self-reported, sustained alleviation of all (COVID-19) symptoms for four consecutive days. In an earlier press release from December 2021, Pfizer had already reported that primary endpoint in EPIC-SR was not met it was important to note that is analysis was based on only 45% of the trial’s planned enrolment total. Now, with an updated analysis of 1,153 patients enrolled through December 2021, the current press release re-affirms, the disappointing results of the earlier, interim analysis. The data show that there was a non-significant 51% relative risk reduction in the primary outcome and in a sub-group analysis of 721 vaccinated adults who had at least one risk factor for progression to severe COVID-19, there was also a 57% non-significant relative risk reduction in hospitalisation or death.

However, not all of the current data is negative. When performing an additional analysis of secondary endpoint data, treatment with Paxlovid resulted in a nominally significant 62% decrease in COVID-19-related medical visits per day across all patients, relative to placebo (p = 0.0228).

Following these results, the press release reports that Pfizer has decided to cease enrolment into EPIC-SR

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