- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD), Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Journal: Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19. (Pubmed Central) - Jun 14, 2024
In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, azvudine (FNC) / Granlen, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Retrospective data, Journal, Real-world evidence, Real-world effectiveness, Real-world: Real-world effectiveness of molnupiravir, azvudine and paxlovid against mortality and viral clearance among hospitalized patients with COVID-19 infection during the omicron wave in China: A retrospective cohort study. (Pubmed Central) - Jun 13, 2024
In our retrospective cohort of hospitalized patients with COVID-19 during the wave of omicron strain, the molnupiravir, paxlovid and azvudine recipients showed a faster and more stable decrease in viral load and rare virus rebound in response to antiviral treatments when compared to the controls. The study supported that initiation treatment with paxlovid and azvudine was associated with significantly lower risk of all-cause death within 28 days.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: SARS-CoV-2 Antiviral Prescribing Gaps Among Non-Hospitalized High-Risk Adults. (Pubmed Central) - Jun 13, 2024
Within a multi-state clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among non-hospitalized SARS-CoV-2-infected patients with risk factors for severe COVID-19. Among 3,247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: High-Resolution Substrate Specificity Profiling of SARS-CoV-2 Mpro; Comparison to SARS-CoV Mpro. (Pubmed Central) - Jun 12, 2024
The SARS-CoV-2 Mpro protease from COVID-19 cleaves the pp1a and pp2b polyproteins at 11 sites during viral maturation and is the target of Nirmatrelvir, one of the two components of the frontline treatment sold as Paxlovid...The population of cleaved substrates isolated in our sorts is so deep, the relative catalytic efficiencies of the different cleavage sites on the SARS-CoV-2 polyproteins pp1a and pp2b are qualitatively predicted. These results not only demonstrated the precise and reproducible nature of the YESS 2.0/NGS approach to protease substrate specificity profiling but also should be useful in the design of next generation SARS-CoV-2 Mpro inhibitors, and by analogy, SARS-CoV Mpro inhibitors as well.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Viral SARS-CoV-2 Rebound Rates in Linked Commercial Pharmacy-Based Testing and Health Care Claims. (Pubmed Central) - Jun 10, 2024
We linked real-time reverse transcription quantitative polymerase chain reaction test data from national pharmacy-based testing to health care claims data via tokenization to calculate the cumulative incidence of viral RNA rebound within 28 days following positive test results in nirmatrelvir/ritonavir (NMV-r)-treated and untreated individuals during the Omicron era (December 2021-November 2022) and prior to the Omicron era (October 2020-November 2021)...Our findings suggest viral RNA rebound is rare (< 5%), with rates that were consistent with those from the EPIC-HR trial (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients). Most occurrences of viral RNA rebound were associated with low viral RNA levels, and viral RNA rebound progression to severe disease was not observed.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, azvudine (FNC) / Granlen
Clinical, Retrospective data, Review, Journal: Azvudine versus Paxlovid in COVID-19: A systematic review and meta-analysis. (Pubmed Central) - Jun 8, 2024
However, azvudine showed better effectiveness in improving other outcomes. Regarding the level of certainty of evidence, further research is needed to validate or challenge these results.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal, Combination therapy: Early combination therapy of COVID-19 in high-risk patients. (Pubmed Central) - Jun 1, 2024
Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.
- |||||||||| Xiannuoxin (simnotrelvir) / Simcere, Shanghai Inst. of Materia Medica, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Effect of use of oral antiviral agents on reducing critical illness and mortality for patients with moderate to severe COVID-19 (PS-25; Poster board no. 11) - May 31, 2024 - Abstract #ERS2024ERS_5025;
No adverse drug reactions were observed during hospitalization, and no new safety events were observed, suggesting the excellent effectiveness and safety of Simnotrelvir/Ritonavir and Nirmatrelvir/Ritonavir in preventing the progression of medium-sized COVID-19 to severe disease. Administering simnotrelvir/ritonavir and nirmatrelvir/ritonavir reduced the risk of moderate to severe COVID-19 patients progressing to critical illness and mortality.
- |||||||||| Xiannuoxin (simnotrelvir) / Simcere, Shanghai Inst. of Materia Medica, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Retrospective analysis on Nirmatrelvir versus Simnotrelvir for adults with moderate to severe COVID-19. (PS-26; Poster board no. 17) - May 31, 2024 - Abstract #ERS2024ERS_1624;
The overall efficacy of the two drugs is comparable, treatment choice should be based on the individual patient's situation and resistance status. These findings provide reference information for clinicians when selecting antiviral treatment regimens.
- |||||||||| Xiannuoxin (simnotrelvir) / Simcere, Shanghai Inst. of Materia Medica, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Outcomes of two kinds of 3CLpro inhibitors in delayed treatment of COVID-19 patients with diabetes (PS-26; Poster board no. 16) - May 31, 2024 - Abstract #ERS2024ERS_1623;
These findings provide reference information for clinicians when selecting antiviral treatment regimens. Compared with Nirmatrelvir/ritonavir, Simnotrelvir/ritonavir is more suitable for antiviral treatment of COVID-19 patients with diabetes.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Supratherapeutic INR During Treatment With Nirmatrelvir/Ritonavir and Warfarin and Acute Illness With COVID-19: A Case Report. (Pubmed Central) - May 28, 2024
Practice Implications: While PK models and case series have hypothesized both potential increases or decreases in INR with the nirmatrelvir/ritonavir and warfarin interaction, COVID-19 infection itself can cause several pharmacodynamic changes which can increase INR, including decreased appetite and, in severe cases, organ dysfunction. This case provides real-world insight into the drug interaction between nirmatrelvir/ritonavir and the drug-disease state interaction between warfarin and COVID-19.
- |||||||||| Prezista (darunavir) / J&J, Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
FDA event, Review, Journal: Pathogenesis of COVID19 and the applications of US FDA-approved repurposed antiviral drugs to combat SARS-CoV-2 in Saudi Arabia: A recent update by review of literature. (Pubmed Central) - May 27, 2024
In this article, several COVID19-related discussions have been provided including emerging variants of concern of, COVID19 pathogenesis, COVID19 pandemic scenario in Saudi Arabia, drug repurposing strategies against SCV-2, as well as repurposing of US FDA-approved antiviral drugs that might be considered to combat SCV-2 in Saudi Arabia. Moreover, drug repurposing in the context of COVID19 management along with its limitations and future perspectives have been summarized.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Preclinical, Journal: The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development. (Pubmed Central) - May 26, 2024
In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Review, Journal: Challenges in Treating Pediatric Cancer Patients during the COVID-19 Pandemic: Balancing Risks and Care. (Pubmed Central) - May 25, 2024
Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.
- |||||||||| Xiannuoxin (simnotrelvir) / Simcere, Shanghai Inst. of Materia Medica, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Thiophene-fused ?-lactams inhibit the SARS-CoV-2 main protease via reversible covalent acylation. (Pubmed Central) - May 24, 2024
We report combined structure activity relationship and mass spectrometric studies revealing that appropriately functionalized ?-lactams can potently inhibit Mpro by reversible covalent reaction with Cys145 of Mpro. The results suggest that ?-lactams have potential as electrophilic warheads for development of covalently reacting small-molecule inhibitors of Mpro and, by implication, other nucleophilic cysteine enzymes.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
PK/PD data, Preclinical, Journal: Pharmacokinetic analysis of antiviral drug ritonavir across the blood-brain barrier and its interaction with Scutellaria baicalensis using multisite microdialysis in rats. (Pubmed Central) - May 21, 2024
Ritonavir, an excellent inhibitor of CYP3A4, has recently been combined with nirmatrelvir to form Paxlovid for the treatment of severe acute respiratory syndrome coronavirus 2 infections...Treatment also boosted the maximum blood concentration of flavones by 1.5-fold and the maximum brain concentration of flavones by 2-fold, all the while exerting no noticeable influence on the transfer ratio across the bloodbrain barrier. These experimental results demonstrated that the use of a typical traditional Chinese medicinal dose of S. baicalensis is sufficient to influence the metabolic pathway and synergistically increase the concentration of ritonavir in rats.
- |||||||||| Fragmin (dalteparin sodium) / Pfizer, Eisai, Innohep (tinzaparin) / LEO Pharma, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Enrollment closed, Trial completion date, Trial primary completion date: Australasian COVID-19 Trial (ASCOT) ADAptive Platform Trial (clinicaltrials.gov) - May 15, 2024
P3, N=2200, Active, not recruiting,
Further evidence is necessary that RdRp inhibitors have a higher safety profile than Paxlovid. Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jul 2025
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Rituxan (rituximab) / Roche
SARS-COV-2 IN PATIENTS WITH ONCOHEMATOLOGIC DISEASES AND HEMATOPOIETIC STEM CELL TRANSPLANTATION (HCT) IN 2023: A MAJOR SHIFT TO MILDER FORMS OF COVID-19 (Poster Area (Hall 7)) - May 15, 2024 - Abstract #EHA2024EHA_4012;
This may be explained by the use of antiviral drugs atthe time of the infection, the universalization of SARS-CoV2 vaccination, as vaccinated individuals may presentwith lower viral loads and a more rapid viral decline; previous exposition to SARS-CoV-2; and by the change ofSARS-CoV-2 variants to low virulence ones, as the rates of hospitalizations and deaths among patients infectedwith these variants seem substantially lower when compared to previous strains. This shift to milder forms ofCOVID-19 after SARS-CoV-2 infection may have implications for the application in the future of furthertreatments like prophylaxis pre-exposition in these, previously considered, high-risk patients for SARS-CoV2complications.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Preclinical, Journal: In-vitro and in-vivo assessment of nirmatrelvir penetration into (Pubmed Central) - May 11, 2024
A median of only 16% of all the predicted CSF concentrations in rats were?>?3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Nulojix (belatacept) / BMS
COVID-19 Infection during Pregnancy in Transplant Recipients (Poster Hall, Exhibit Hall A, Level 2) - May 6, 2024 - Abstract #ATC2024ATC_983;
To date recipients have not reported any graft loss related to COVID-19 post-pregnancy. Additionally, no sequelae of in utero COVID-19 exposure or anti-COVID-19 treatment have been noted in the children.
- |||||||||| Comparative Effectiveness of Outpatient COVID-19 Therapies in Solid Organ Transplant Recipients (Poster Hall, Exhibit Hall A, Level 2) - May 6, 2024 - Abstract #ATC2024ATC_904;
SOTRs who received outpatient mAb or antiviral treatment for mild-to-moderate COVID-19 had comparable clinical outcomes, as measured by odds of hospitalization. Clinicians may use any of these treatment options according to the individual patient's circumstances and without concern for differential therapeutic efficacy.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Nirmatrelvir/Ritonavir versus Remdesivir in Kidney Transplant Recipients: A Retrospective Study (Poster Hall, Exhibit Hall A, Level 2) - May 6, 2024 - Abstract #ATC2024ATC_252;
No difference was observed between the two agents in reducing mortality within 28 days post-treatment. COVID-19 treatment choice in this population might also be influenced by factors such as drug-drug interactions, medication administration, kidney function, and cost.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in CKD Patients With COVID-19. (Pubmed Central) - May 6, 2024
The nirmatrelvir-ritonavir trial also showed reduced risk for those who had antiviral treatment and received 3 or more vaccine doses. Both molnupiravir and nirmatrelvir-ritonavir reduced mortality rates for hospitalized COVID-19 patients with CKD.
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