Pfizer Reports Paxlovid Reduces Hospitalization or Death Risk by Nearly 90% in High-Risk COVID-19 Patients

Oral antiviral therapies for COVID-19 allow patients to take them at home as soon as initial symptoms appear or upon detection of infection, potentially reducing the risk of disease progression leading to hospitalization or death. Thus, like COVID-19 vaccines, neutralizing antibodies, and other measures, they are an important tool in the "toolkit" for combating the pandemic.

Today, Pfizer Inc. announced the latest clinical trial results of its oral anti-COVID-19 therapy Paxlovid. In a Phase 2/3 clinical trial for treating high-risk patients who could develop severe COVID-19, the final analysis showed that Paxlovid reduced the risk of hospitalization or death by nearly 90%. Another Phase 2/3 clinical trial indicated that in populations with a lower risk of developing severe illness, Paxlovid still reduced the risk of hospitalization or death by 70%. Additionally, in vitro biochemical experiments suggest that Paxlovid has the potential to maintain strong antiviral activity against various SARS-CoV-2 variants, including Omicron.

Final analysis of clinical trials conducted in COVID-19 patients at high risk of progressing to severe disease showed that 0.7% (5/697) of patients in the Paxlovid group required hospitalization within 3 days after symptom onset, with no deaths. In the placebo group, 6.5% (44/682) required hospitalization, and 9 patients later died. Paxlovid reduced the risk of hospitalization or death by 89% in this patient population.

Within 5 days of symptom onset, 0.8% (8/1039) of patients in the Paxlovid group required hospitalization, with no deaths reported. In the placebo group, 6.3% (66/1046) required hospitalization, and 12 patients later died. Paxlovid reduced the risk of hospitalization or death by 88% in this patient population.

External experts said that the effects of receiving treatment within 3 days and within 5 days of symptom onset are similar, meaning diagnosed patients have more opportunities to receive drug treatment.

In this clinical trial, researchers measured the viral load of 499 patients at baseline and after 5 days of treatment. The results showed that, compared with the placebo, Paxlovid reduced the viral load in patients by approximately 10 times (0.93 log10 copies/mL).

In another phase 2/3 clinical trial, adult COVID-19 patients who were unvaccinated against COVID-19 but had no risk factors for developing severe illness (including being over 65 years old, obesity, or having underlying conditions, etc.), and those who were vaccinated but carried at least one risk factor for severe illness, received treatment with Paxlovid or a placebo. These patients had a relatively lower risk of progressing to severe disease. In this patient population, compared to placebo, Paxlovid reduced the risk of hospitalization by 70% and decreased the viral load by approximately 10 times (1 log10 copies/mL).

This clinical trial also analyzed whether Paxlovid treatment could continuously alleviate COVID-19 symptoms for four consecutive days. According to the results self-reported by patients, the clinical trial failed to reach this primary endpoint.

Paxlovid consists of the SARS-CoV-2 3CL protease inhibitor nirmatrelvir (PF-07321332) and the antiviral agent ritonavir. Nirmatrelvir blocks the activity of the SARS-CoV-2 3CL protease, preventing the subsequent RNA replication process of the virus. A low dose of ritonavir helps reduce the metabolism or degradation of nirmatrelvir, keeping it active in the body for a longer period to help combat the virus.

Multiple SARS-CoV-2 variants of concern may develop resistance to preventive or therapeutic interventions targeting the viral spike protein, whereas nirmatrelvir targets the viral protease. Pfizer noted that in vitro biochemical assays demonstrated potent inhibition of the 3CL protease of the Omicron variant by nirmatrelvir. This suggests that nirmatrelvir has the potential to exhibit strong antiviral activity against the Omicron variant. Currently, scientists are conducting additional in vitro antiviral assays.

References:

[1] Pfizer Announces Additional Phase 2/3 Study Results Confirming Robust Efficacy of Novel COVID-19 Oral Antiviral Treatment Candidate in Reducing Risk of Hospitalization or Death. Retrieved December 14, 2021, from https://www.businesswire.com/news/home/20211214005548/en/

[2] Pfizer’s Covid pill remains 89% effective in final analysis, company says. Retrieved December 14, 2021, from https://www.statnews.com/2021/12/14/pfizers-covid-pill-remains-89-effective-in-final-analysis-company-says/

(Original text has been abridged)

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