Vericiguat, a First-in-Class sGC Stimulator by Bayer and Merck, Significantly Reduces Risk of Heart Failure Hospitalization or Cardiovascular Death in High-Risk HFrEF Patients

March 29, 2020 News /BioonBIOON/ --Bayer(Bayer) and Merck & Co. recently jointly announced detailed data from the Phase III VICTORIA study (NCT02861534) of vericiguat for the treatment of heart failure. The drug is an oral soluble guanylate cyclase (sGC) stimulator currently being developed for the treatment of patients with heart failure with reduced ejection fraction (HFrEF) following a worsening event.VICTORIA is the first contemporary outcomes study specifically targeting patients with symptomatic chronic heart failure (ejection fraction <45%) who have experienced a worsening event. The results showed that, when used in combination with available heart failure medications, compared with placebo,Vericiguat significantly reduced the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with chronic heart failure (ejection fraction <45%) following a worsening event.

These results were presented at the American College of Cardiology’s Annual Scientific Session held recentlyMeetingpresented at the World Congress of Cardiology (ACC.20/WCC Virtual) and published in the New England Journal of Medicine (NEJM), a top-tier international medical journal. The article is titled:Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction。

VICTORIA was a randomized, placebo-controlled, parallel-group, multicenter, double-blind Phase III study conducted at more than 600 clinical centers across 42 countries worldwide. The study enrolled a total of 5,050 patients who were at high risk of hospitalization and cardiovascular death following a recent episode of heart failure decompensation. In the study, patients were randomly assigned to receive once-daily vericiguat (titrated to 10 mg; n=2,526) or placebo (n=2,524), in addition to standard-of-care heart failure therapy.

The results demonstrated that the study met its primary efficacy endpoint: in patients with heart failure with reduced ejection fraction (HFrEF) who had experienced a worsening event, vericiguat, when added to available heart failure therapies, reduced the risk of the composite endpoint of heart failure hospitalization or cardiovascular death compared with placebo. Specifically, over a median treatment duration of 10.8 months, cardiovascular death or heart failure-related hospitalization occurred in 35.5% (897 patients) of the vericiguat group and 38.5% (972 patients) of the placebo group.

Compared with placebo,Vericiguat significantly reduced the risk of the composite endpoint in this high-risk population (hazard ratio [HR]=0.90; 95% CI: 0.82-0.98; p=0.019).An HR of 0.90 translates to a clinically relevant absolute reduction in event rate of 4.2 per 100 patient-years. This effect was consistent across most prespecified subgroups, including patients receiving or not receiving Entresto (sacubitril/valsartan). Baseline NT-proBNP levels and age were associated with treatment efficacy. Data from this study suggest that patients with lower baseline NT-proBNP levels (in the lower quartiles) and those aged under 75 years may have derived greater benefit.

In this study, the safety profile of vericiguat was consistent with previous studies. The overall incidence of serious adverse events was similar between the vericiguat group and the placebo group (32.8% vs. 34.8%). Symptomatic hypotension (9.1% vs. 7.9%) and syncope (4.0% vs. 3.5%) were more common in the vericiguat group than in the placebo group, but the differences were not statistically significant.

Dr. Paul W. Armstrong, a cardiologist at the University of Alberta and the study’s reporting author, stated, “For this group of patients with chronic heart failure who are at high risk for future events, vericiguat has demonstrated its potential to serve as an important new addition to standard guideline-directed therapy, particularly in a context where few other drugs have been studied. We are encouraged by the observed absolute risk reduction and hope that these findings will open up a new avenue for appropriate heart failure patients, while also paving the way for future discoveries in cardiovascular disease.”

Heart Failure with Reduced Ejection Fraction (HFrEF), formerly known as systolic heart failure, is characterized by impaired ability of the heart to eject blood adequately during systole. In the United States, 6.5 million people have heart failure, and approximately 40–50% of these patients have HFrEF. Each year, about 30% of patients with symptomatic chronic heart failure experience disease worsening, characterized by progressive symptoms and/or a recent heart failure event. Approximately half of patients with worsening chronic HFrEF are readmitted within 30 days after deterioration, and an estimated one in five will die within two years.

Since October 2014, Bayer and Merck Sharp & Dohme have entered into a global collaboration to develop sGC stimulators. The vericiguat (BAY1021189/MK-1242) program is being jointly developed by both parties.Vericiguat is an oral direct stimulator of soluble guanylate cyclase (sGC). Although sGC plays a critical role in vascular and cardiac function, impaired nitric oxide (NO) bioavailability in patients with heart failure leads to insufficient sGC stimulation, resulting in myocardial and vascular dysfunction. Vericiguat is a first-in-class sGC stimulator in late-stage clinical development for the treatment of heart failure. (Bioon.com)

Original Source:Investigational Drug Vericiguat Significantly Reduced the Risk of the Composite Endpoint of Heart Failure Hospitalization or Cardiovascular Death, Compared to Placebo, When Given in Combination with Available Heart Failure Therapies