Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19.

Background: Clinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis.

Methods: We conducted a phase 2-3 double-blind trial to assess the efficacy and safety of nirmatrelvir-ritonavir in asymptomatic, rapid antigen test-negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir-ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days.

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis.

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19.

Background: Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.

Methods: In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days.

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

Background & Aims: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.

Methods: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4.

Population PK/PD modeling of low-density lipoprotein cholesterol response in hypercholesterolemic participants following administration of bococizumab, a potent anti-PCSK9 monoclonal antibody.

We sought to characterize the population pharmacokinetic/pharmacodynamic (PK/PD) relationship of bococizumab (RN316/PF-04950615), a humanized IgG2Δa monoclonal antibody that binds to secreted human proprotein convertase subtilisin kexin type 9 (PCSK9), using data derived from 16 phase I, II, and III clinical studies (36,066 bococizumab observations, 46,790 low-density lipoprotein cholesterol [LDL-C] measurements, 3499 participants). A two-compartment disposition model with parallel linear and Michaelis-Menten elimination and an indirect response model was used to characterize the population PK and LDL-C response of bococizumab. Potential model parameters and covariate relationships were explored, and visual predictive checks were used for model assessment and validation.