New crown oral drug!Pfizer’s Paxlovid (nirmatrelvir/ritonavir) was recommended for approval by the EU CHMP! – Pfizer Zone – Bio Valley

Paxlovid is a combination formulation consisting of 300mg (2 tablets of 150mg) nirmatrelvir and one tablet of ritonavir 100mg taken 2 times a day for 5 consecutive days. One box of the drug contains 5 blister packs of Paxlovid as a combined package of nirmatrelvir tablets and ritonavir tablets to provide the full dose required for a full 5-day efficacy.

The positive review opinion of the EU CHMP and the US EUA, based on data from the Phase 2/3 EPIC-HR study:Compared to placebo, Paxlovid reduced the risk of hospitalization or death by 89% (treatment initiation within 3 days of symptom onset) and 88% (treatment initiation within 5 days of symptom onset)。

Among the active pharmaceutical ingredients of Paxlovid, nirmatrelvir is a novel master protease (Mpro, also known as 3CL protease) inhibitor from Pfizer Laboratories, specifically designed to block the activity of SARS-CoV-2 Mpro, the enzyme required for the coronavirus to replicate. Low-dose ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir, allowing it to remain active in the body for longer at higher concentrations to help fight the virus.

The current mutant strain is resistant to drugs that inhibit the spike protein on the surface of the SARS-COV-2 virus because of its high mutation rate. However, Paxlovid works inside cells by binding to the protease of the SARS-CoV-2 virus, thereby inhibiting viral replication. nirmatrelvir showed consistent in vitro antiviral activity against current variant strains (ie, alpha, beta, delta, gamma, lambda, and mu). In addition, nirmatrelvir effectively inhibited Mpro associated with Omicron in in vitro biochemical assays. This suggests that nirmatrelvir has the potential to maintain potent antiviral activity against Omicron. Additional in vitro antiviral studies of this variant are ongoing.

Image credit (healthiyer.com)

The Phase 2/3 EPIC-HR trial enrolled non-hospitalized adult patients 18 years of age and older with confirmed COVID-19 who were at increased risk for progression to severe disease. The data showed that patients who received Paxlovid had an 89% lower risk of hospitalization or death from any cause compared with placebo (primary endpoint) when treatment was initiated within 3 days of symptom onset. By day 28, no patients in the Paxlovid-treated group had died, compared with nine in the placebo group. Similar results were observed when treatment was initiated within 5 days of symptom onset (a secondary endpoint), with Paxlovid-treated patients having an 88% lower risk of hospitalization or death from any cause compared with placebo, and no deaths were observed. Treatment-period adverse events (TEAEs) were comparable between the Paxlovid group (23%) and the placebo group (24%), the majority of which were mild.