Contemporary Accounts in Drug Discovery and Development

The phase III VICTORIA trial successfully met its primary endpoint. Vericiguat treatment significantly reduced the composite endpoint CV death and HF hospitalization upon 10.8 months median treatment duration in patients with HF and reduced ejection fraction. The placebo event rate in these patients who were enrolled within six months of a previous HF event (that could have been an HF hospitalization or i.v. diuretic treatment for HF) was 37.8 per 100 patient years. In the vericiguat arm, this was significantly reduced to 33.6, reflecting an absolute risk reduction of 4.2% per year for the dual composite primary endpoint of CV death or HF hospitalization [5]. Thus, in this population of patients at high risk of events, veriguat treatment is the first new drug candidate directly targeting the sGC pathway that showed a significant improvement in outcomes when combined with other HF therapies. Importantly, background HF therapy in 15% of studied patients included the combination with sacubitril/valsartan, in whom the efficacy of vericiguat to reduce the risk for the primary composite was no less than in the overall population.

Vericiguat belongs to a novel class of drugs termed sGC stimulators. Vericiguat selectively and specifically binds to sGC leading to concentration‐dependent production of the second messenger cGMP. Since NO/sGC signaling is impaired in CV diseases and HF, vericiguat can restore this dysfunctional NO/sGC signaling. Preclinical and clinical data strongly suggest that vericiguat as confirmed in the recent VICTORIA phase 3 trial does improve clinical outcomes in patients with HF and maybe other CV diseases.

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