It was found to reduce the progression and mortality of SARS-CoV-2 Mpro inhibitor, phi matrrelvir, COVID-19.

In a recent study published in New England Journal of Medicine, A team of Pfizer researchers in the United States (US) have found the efficacy and safety of phi matrrelvir in patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk of progressing to severe COVID-19 disease. Was evaluated.

Recent studies have shown that patients with certain pre-existing conditions (old age, smoking, diabetes, obesity, cardiovascular disease, cancer, etc.) are at increased risk, twice as likely to progress to severe COVID-19, and are vulnerable. Has been found to be five times higher. Death compared to those without these conditions. Nirmatorelvir is the major protease (M) of coronavirus 2 (SARS-CoV-2) in severe acute respiratory syndrome.^Professional) Inhibitory activity.

In the current study, a team of researchers conducted a randomized, double-blind, placebo-controlled phase 2-3 clinical trial to determine the efficacy and viral load of nilmatrelvir and ritonavir (pharmacokinetic enhancer). , And estimated safety data. -Vaccinated, symptomatic, unhospitalized COVID-19 patients at risk of developing severe COVID-19 disease from different countries.

Research design

Eligible patients were randomly assigned using an interactive response technology system and received a 1: 1 ratio of nilmatrelvir (300 mg) to ritonavir (100 mg), or placebo every 12 hours for 5 days. rice field. The team estimated the SARS-CoV-2 viral load in the nasopharyngeal swab through a reverse transcriptase polymerase chain reaction (RT-PCR) assay. End drug safety information endpoints, including adverse events, serious adverse events, and adverse events leading to study drug or placebo discontinuation, were evaluated up to day 34 and were evaluated in version 24.0 of the Medical Dictionary for Regulatory Activities (MedDRA). Coded according to.

An interim analysis of the key endpoints was performed based on a sequential group design using the Lan-DeMets alpha spending function with O’Brien-Fleming stop boundaries.

Survey results

The median age of enrolled patients was 46 years, and the cohort consisted of 51.1% male, 71.5% Caucasian, and 14% Asian patients. Among patients at relative risk of developing COVID-19 severe disease, the most common coexisting clinical features and comorbidities are body mass index (BMI) ≥25 (80.5%), smoking (39%), and hypertension. (32.9%), and two or more other functions or coexisting parameters (61%). In randomization, the majority of enrolled patients (93.8%) did not receive the COVID-19 monoclonal antibody, and 66.3% received the study drug or placebo within 3 days of the onset of symptoms. ..

In the primary interim analysis, recipients of nilmatrelvir and ritonavir who started treatment within 3 days of onset of symptoms had 0.77% of COVID-19-related hospitalizations by day 28 compared to 7.01% in the placebo group. Or it showed a mortality rate and revealed that the relative risk was reduced by 89.1. %.

In patients who started treatment within 3 and 5 days of onset of symptoms but did not receive the monoclonal antibody, 0.72% and 0.77% of the recipients in the Nilmatrelvir group, respectively, compared to 6.45% for COVID-. He was hospitalized or died by 19. The event rates for COVID-19-related hospitalization for some reason in the Nilmatrelvir and placebo groups treated within 5 days of onset were 0.72% and 6.53%, respectively. The relative risk reductions due to nilmatrelvir observed on days 3 and 5 of treatment initiation were 88.9% and 87.8%, respectively.

After including patients who received or will be treated with monoclonal antibodies, the treatment groups of nilmatrelvir and ritonavir and placebo for some reason caused 0.81% and 6.10% of COVID-19-related hospitalizations and deaths, respectively. was.

When treatment was started within 3 and 5 days of onset of symptoms, the researchers found that the nilmatrelvir and ritonavir groups reduced SARS-CoV-2 viral load with an additional 0.868 ± 0.105 log adjusted average. I showed that._Ten Number of copies per ml and 0.695 ± 0.085 logs_Ten Number of copies per ml each.

Similarly, including patients who received or will receive monoclonal antibodies to treat COVID-19, treatment with nirmatorelvir and ritonavir further increased SARS-CoV-2 viral load by 0.689 ± 0.082. log has decreased._Ten Number of copies per ml on day 5 compared to placebo.

Recipients of nirmatorelvir and ritonavir and placebo induced 22.6% and 23.9% of similar adverse events during and after treatment, respectively. The percentage of the most frequently observed events affecting approximately 1% of patients in the ilmatrelvir and ritonavir treatment groups was dysgeusia (5.6%), diarrhea (3.1%), and increased fibrin. D-dimer (1.9%), increased alanine aminotransferase (1.5%), headache (1.4%), decreased creatinine and renal clearance (1.4%), nausea (1.4%), and vomiting (1.1%), these in the placebo group Of the events, 0.3%, 1.6%, 2.8%, 2.4%, 1.3%, 1.6%, 1.7% and 0.8%, respectively. All adverse events were not serious and were classified as 1 or 2.

Adverse events were more common in the nirmatorelvir and ritonavir groups (7.8%) compared to placebo (3.8%), and dysgeusia (4.5%) and diarrhea compared to placebo (0.2% for both). There was a difference mainly due to (1.3%).

Researchers found that the Nilmatrelvir and ritonavir groups had fewer grade 3 or 4 adverse events, fewer serious adverse events, and fewer side effects that caused drug discontinuation compared to placebo recipients. Observed (4.1%, 1.6%, 2.1%, respectively). 8.3%, 6.6%, 4.2%, respectively).

The most frequent adverse events reported in the recipients of the nilmatrelvir and ritonavir groups were reduced creatinine clearance (respectively) compared to COVID-19-induced pneumonia, COVID-19, and placebo recipients (3.3%). It was 0.5%, 0.2%, 0.2%). , 0.7% and 0.3%, respectively), according to the investigator, there were no adverse events associated with Nilmatrelvir.

Notably, the researchers analyzed that no serious adverse event-induced deaths were observed in the Nirmatrelvir group, but 13 COVID-19-related deaths occurred in the placebo group. ..

Conclusion

The results of this study have shown to be remarkable. Effectiveness of Treatment of oral nirmatorelvir and ritonavir in symptomatic mild to moderate COVID-19 patients slows the progression to severe COVID-19 and rapidly reduces viral load.

In addition, the combination of nirmatorelvir and ritonavir has fewer adverse events and is more likely to be more effective against future SARS-CoV-2 mutants.