FDA approves sGC stimulator for treatment of HFrEF patients

The FDA approved the soluble guanylate cyclase (sGC) stimulator vericiguat to reduce risk of CV death and heart failure (HF) hospitalization following a hospitalization for HF or need for outpatient IV diuretics in adults with symptomatic chronic HF and ejection fraction <45%. This decision is based on the results of the phase 3 VICTORIA trial.

This decision was based on data from the phase III VICTORIA study, presented at the ACC.20/WCC Virtual Congress and published in the NEJM. VICTORIA was a randomized, parallel-group, placebo-controlled, double-blind, event-driven, multi-center clinical trial comparing the effect of vericiguat to placebo in 5050 patients with symptomatic chronic HF (NYHA class II-IV) and LVEF <45% following a worsening HF event. The primary endpoint was a composite of time to first event of CV death or hospitalization for HF. Median follow-up for the primary endpoint was 11 months. Vericuguat reduced the combined risk of first hosptalization for HF or CV death compared to placebo.

Adverse profile of vericiguat was similar to that of placebo. The adverse drug reactions occurring more frequently with vericiguat than placebo in VICTORIA were hypotension (16% vs. 15%) and anemia (10% vs. 7%).

Vericiguat is a stimulator of sGC, an enzyme in the nitric oxide (NO) signaling pathway. Binding of NO to sGC results in synthesis of intracellular cyclic guanosine monophosphate (cGMP). cGMP plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with decrease synthesis of NO and decreased activity of sGC. Vericiguat can by directly stimulating sGC augment levels of intracellular cGMP resulting in smooth muscle relaxation and vasodilation.

Source: press release Merck, January 20, 2021 Source: press release Bayer, January 20, 2021