fosdagrocorat (PF-04171327) / Pfizer - LARVOL DELTA

A Study Of PF-04171327 In The Treatment Of The Signs And Symptoms Of Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=86 | Completed | Sponsor: Pfizer | Phase classification: P2a ➔ P2

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Biased regulation of glucocorticoid receptors signaling. (PubMed, Biomed Pharmacother) - "Based on the bias regulation of GR, selective GR agonists and modulators (SEGRAMs) were developed to bias therapeutic outcomes toward expected outcomes (e.g., anti-inflammation and immunoregulation) by influencing GR-mediated gene expression. This paper provides a review of the bias regulation and mechanism of GR and the research progress of drugs."

Journal • Review • Immune Modulation • Inflammation

JTP-117968, a novel selective glucocorticoid receptor modulator, exhibits significant anti-inflammatory effect while maintaining bone mineral density in mice. (PubMed, Eur J Pharmacol) - "Remarkably, CIA development was suppressed by JTP-117968 comparably with prednisolone and PF-802, an active form of fosdagrocorat that has been developed clinically as an orally available SGRM. Strikingly, the side effect of JTP-117968 on mouse femoral BMD was much lower than those of PF-802 and prednisolone. Therefore, JTP-117968 has attractive potential as a new therapeutic option against inflammatory diseases with minimized side effects compared to classic glucocorticoids."

Journal • Diabetes • Immunology • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Osteoporosis • Rheumatoid Arthritis • Rheumatology • TNFA

Dimerization of glucocorticoid receptors and its role in inflammation and immune responses. (PubMed, Pharmacol Res) - "Furthermore, some studies have shown that some selective glucocorticoid receptor agonists and modulators (SEGRAMs) have good separation characteristics (i.e., preferentially mediate the transrepression of proinflammatory genes or preferentially activate anti-inflammatory target genes). This article reviewed the formation of GR dimers, the role of GR dimers in the inflammation and immune responses, and the progress of SEGRAMs to provide novel ideas for further understanding the anti-inflammatory mechanism of GR and the development of SEGRAMs."

Journal • Review • Allergic Rhinitis • Asthma • Immunology • Inflammation • Inflammatory Arthritis • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Predicting the probability of successful efficacy of a dissociated agonist of the glucocorticoid receptor from dose-response analysis. (PubMed) - "PF-04171327 is a dissociated agonist of the glucocorticoid receptor (DAGR) being developed to retain anti-inflammatory efficacy while reducing unwanted effects...The data included were from a Phase 2, randomized, double-blind, parallel-group study in 323 subjects with active rheumatoid arthritis on a background of methotrexate...DAGR 9 mg estimated probability was 50 % suggesting that DAGR ≥9 mg QD has an effect on DAS28-4 CRP comparable to or greater than prednisone 10 mg QD. This work informs dose selection for late-stage confirmatory trials."

Journal • Biosimilar • Immunology • Inflammation • Rheumatoid Arthritis

Pfizer: Pipeline Update (Pfizer) - Pfizer discontinued the development of PF-04171327 in rheumatoid arthritis since February 2, 2016

Discontinued • Rheumatoid Arthritis

In Vitro and In Vivo Investigation of Potential for Complex CYP3A Interaction for PF-00251802 (Dagrocorat), a Novel Dissociated Agonist of the Glucocorticoid Receptor. (PubMed, Clin Pharmacol Drug Dev) - P1; "Administration of midazolam alone or concomitantly with PF-04171327 resulted in equivalent pharmacokinetic profiles (AUCinf , 21.17 vs 20.28 ng·h/mL, respectively), indicating that PF-04171327 had no net effect on CYP3A activity in vivo. These findings support the further development of PF-00251802 and PF-04171327 as potential treatments for patients with rheumatoid arthritis (NCT00987038)."

Journal • Preclinical

Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a randomised, double-blind, multicentre, phase IIb study. (PubMed, RMD Open) - P2; "In patients with RA, fosdagrocorat 10 mg and 15 mg demonstrated efficacy similar to prednisone 10 mg and safety similar to prednisone 5 mg. NCT01393639."

Biomarker • Clinical • Journal • P2b data