BAY 1128688 / Bayer - LARVOL DELTA

Quantitative Systems Toxicology identifies independent mechanisms for hepatotoxicity and bilirubin elevations due to AKR1C3 Inhibitor BAY1128688. (PubMed, Clin Pharmacol Ther) - "The predicted dose-dependent intrinsic hepatotoxicity may increase patient susceptibility to an adaptive immune response, accounting for ALT elevations observed after completion of treatment. These BAY1128688 simulations provide insight into the mechanisms behind hepatotoxicity and bilirubin elevations and may inform the potential risk posed by future compounds."

Journal • Hepatology • Liver Failure • AKR1C3

Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis. (PubMed, Drugs R D) - P2 | "The hepatotoxicity of BAY1128688 observed in AKRENDO1 was not predicted by animal studies nor by studies in healthy volunteers. However, in vitro interactions of BAY1128688 with bile salt transporters indicated a potential risk factor for hepatotoxicity at higher doses. This highlights the importance of in vitro mechanistic and transporter interaction studies in the assessment of hepatoxicity risk and suggests further mechanistic understanding is required."

Journal • P2a data • Endometriosis • Gynecology • Hepatology • Pain • Women's Health • AKR1C3

Novel AKR1C3 inhibitor affects androgen metabolism but not ovarian function in healthy women: A phase 1 study. (PubMed, Eur J Endocrinol) - "Serum androsterone was identified as a robust response biomarker for AKR1C3 inhibitor treatment in women. AKR1C3 inhibitor administration for 4 weeks did not affect ovarian function."

Journal • P1 data • Endometriosis • Gynecology • Polycystic Ovary Syndrome • Women's Health • AKR1C3

AKRENDO1: A Study to Test Whether Study Drug BAY1128688 Brings Pain Relief to Women With Endometriosis and if so to Get a First Idea Which Dose(s) Work Best (clinicaltrials.gov) - P2; N=121; Terminated; Sponsor: Bayer; Active, not recruiting ➔ Terminated; Study BAY1128688/17472 (AKRENDO 1) was terminated early on 20 July 2018 due to hepatotoxicity

Trial termination • Biosimilar • CNS Disorders • Endometriosis • Gynecology • Pain • Women's Health

Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of BAY1128688 After Multiple Oral Administrations in Healthy Women (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: Bayer; Not yet recruiting -> Recruiting

Enrollment open • Biosimilar • Endometriosis