The Committee for Medicinal Products for Human Use ( CHMP ) of the European Medicines Agency ( EMA ) has granted a positive opinion for Vericiguat ( Verquvo ), a soluble guanylate cyclase ( sGC ) stimulator, in the European Union.
Vericiguat ( 2.5 mg, 5 mg, and 10 mg ) is indicated for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction who are stabilised after a recent decompensation event requiring intravenous ( IV ) therapy.
Even when taking guideline-based therapy, many heart failure patients still experience progressive worsening of symptoms, meaning hospitalization or initiation of intravenous diuretics is needed.
The positive CHMP opinion is based on the results of the pivotal phase III VICTORIA trial, published in The New England Journal of Medicine ( NEJM ) in March 2020.
VICTORIA was a randomized, parallel-group, placebo-controlled, double-blind, event-driven, multi-center clinical trial comparing Vericiguat to placebo in 5,050 adult patients with symptomatic chronic heart failure ( NYHA class II-IV ) and left ventricular ejection fraction ( LVEF ) less than 45%, following a worsening heart failure event. A worsening heart failure event was defined as heart failure hospitalization within six months or less prior to randomization or use of outpatient IV diuretics for heart failure within three months or less prior to randomization.
In VICTORIA, the primary endpoint was a composite of time to first event of cardiovascular death or hospitalization for heart failure.
Patients received up to the target maintenance dose of Vericiguat 10 mg once daily or matching placebo. Therapy was initiated at Vericiguat 2.5 mg once daily and increased in approximately two-week intervals to 5 mg once daily and then 10 mg once daily, as tolerated. Placebo doses were similarly adjusted. After approximately one year, 90% of patients in both the Vericiguat and placebo arms were treated with the 10 mg target maintenance dose.
Vericiguat met the primary efficacy objective based on a time-to-event analysis ( hazard ratio [ HR ]: 0.90, 95% confidence interval [ CI ], 0.82-0.98; p=0.019 ).
Over the course of the study, there was a 4.2% reduction in annualized absolute risk with Vericiguat compared with placebo.
Therefore, 24 patients would need to be treated over an average of one year to prevent one primary endpoint event.
Vericiguat 2.5 mg, 5 mg, and 10 mg is an oral once daily stimulator of soluble guanylate cyclase, an important enzyme in the nitric oxide ( NO ) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate ( cGMP ), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling.
Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction.
By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation. ( Xagena )
Source: Bayer, 2021