Vericiguat clinical pharmacology programme: biopharmaceutical properties and potential intrinsic and extrinsic factor effects

Introduction The Phase III VICTORIA study (NCT02861534), which evaluated vericiguat vs placebo in patients with worsening chronic heart failure (WCHF) with ejection fraction <45%, demonstrated a significant reduction in the primary composite endpoint of cardiovascular death and HF hospitalisation. Purpose A comprehensive clinical pharmacological programme of 28 Phase I trials in >650 participants was performed to inform use of vericiguat. Methods Biopharmaceutical properties, pharmacokinetics (PK) and the potential for intrinsic factors to influence vericiguat dose administration were investigated. The PK and pharmacodynamic (PD) interaction potential of vericiguat with other drugs was assessed. Results Vericiguat had a mean half-life of approximately 24 h and high bioavailability when taken with food, leading to the recommendation of once daily dosing with food. Due to the multi-pathway metabolism and excretion profile of vericiguat, there was a low risk of PK drug–drug interactions (DDI; Table). No clinically relevant PD DDI were identified between vericiguat and aspirin, warfarin, sacubitril/valsartan or nitrates. There was a relatively minor influence of intrinsic factors on vericiguat PK. Conclusion This clinical pharmacology programme supports use of vericiguat in patients with WCHF who are characterised by multiple comorbidities and polypharmacy. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Funding for this research was provided by Bayer AG, Berlin, Germany and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA