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

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the presentation of results from the VICTORIA trial, a Phase 3 study evaluating the efficacy and safety of its investigational drug vericiguat, an orally administered soluble guanylate cyclase (sGC) stimulator being developed to treat patients with heart failure with reduced ejection fraction and following a worsening event. VICTORIA is the first contemporary outcomes study focused exclusively on symptomatic chronic heart failure patients (ejection fraction <45%) following a worsening event. Vericiguat is being jointly developed with Bayer AG.

Patients enrolled in VICTORIA were at high risk of hospitalization and cardiovascular death following a recent heart failure decompensation. Vericiguat, when given in combination with available heart failure therapies, met the primary efficacy endpoint of reducing the risk for the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF), compared to placebo. A hazard ratio of 0.90 (95% CI 0.82-0.98) in this high risk population translated into a clinically relevant 4.2/100 patient-years absolute reduction in event rate. Based on this absolute risk reduction, the number needed to treat with vericiguat for one year to prevent a primary outcome event is approximately 24 patients.

“For this group of chronic heart failure patients at high risk for future events, vericiguat has the potential to provide a significant addition to usual guideline-based treatment,” said Paul W. Armstrong, M.D., cardiologist and Distinguished University Professor of Medicine at the Canadian VIGOUR Centre, University of Alberta, the study’s lead author. “We are pleased with the observed absolute risk reduction and are hopeful that this result may open up a new avenue for appropriate patients and a possible path for future discovery in cardiovascular heart disease.”

“VICTORIA builds on Merck’s strong legacy of conducting large cardiovascular outcomes studies designed to answer meaningful questions. By enrolling patients receiving heart failure therapy following intervention for a worsening event such as rehospitalization or urgent outpatient treatment, VICTORIA was designed to study a serious medical problem not studied in any other recent heart failure outcomes study,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “In the VICTORIA trial, vericiguat met its primary endpoint, achieving a significant reduction in the risk of cardiovascular death and hospitalization for heart failure in these patients overall when given in combination with available heart failure therapies.”

The safety profile of vericiguat was consistent with that reported in previous studies.

These results were presented today at the virtual American College of Cardiology’s 69^th Annual Scientific Session Together With World Congress of Cardiology (ACC.20/WCC) and published in The New England Journal of Medicine.

Merck and Bayer plan to share VICTORIA data with regulatory authorities worldwide.

Study design and additional data from the VICTORIA trial (NCT02861534)

VICTORIA is a randomized, placebo-controlled, parallel-group, multi-center, double-blind, Phase 3 study of vericiguat versus placebo when given in combination with available heart failure therapies in patients with worsening chronic heart failure (New York Heart Association class II-IV), a reduced left ventricular ejection fraction of <45% within 12 months prior to randomization, and elevated natriuretic peptide levels (determined by sites) within 30 days prior to randomization. For patients in sinus rhythm, plasma B-type natriuretic peptide (BNP) levels ≥300 pg/ml and NT-proBNP levels ≥1000 pg/ml were required. For those in atrial fibrillation, BNP levels ≥500 pg/ml and NT-proBNP ≥1600 pg/ml were required. Patients were required to have evidence of worsening heart failure and were classified into three cohorts based on the timing of their symptomatic worsening: <3 months; 3–6 months after hospitalization; and those receiving intravenous diuretic therapy, without hospitalization, within the prior 3 months.

The primary endpoint of the study is the composite of time to first occurrence of heart failure hospitalization or cardiovascular death. Secondary endpoints include time to occurrence of cardiovascular death, time to first occurrence of heart failure hospitalization, time to total heart failure hospitalizations (including first and recurrent events), time to the composite of all-cause mortality or heart failure hospitalization, and time to all-cause mortality.

The study enrolled a total of 5,050 patients who were randomized to receive either vericiguat once daily (titrated up to 10 mg) (n=2,526) or placebo (n=2,524) when given in combination with available heart failure therapies. The study, which was co-sponsored by Merck and Bayer, was conducted in collaboration with the Canadian VIGOUR Centre and the Duke Clinical Research Institute at more than 600 centers in 42 countries.

Over a median of 10.8 months, the incidence of cardiovascular death or heart failure-related hospitalization occurred in 897 (35.5%) patients receiving vericiguat and 972 (38.5%) receiving placebo (HR 0.90; 95% CI 0.82–0.98; P=0.019). This effect was consistent across the majority of pre-specified subgroups, including patients receiving or not receiving sacubitril/valsartan. Levels of NT-proBNP at baseline and age were shown to correlate with the treatment effect. Here, the data suggest that the majority of patients in the study with NT-proBNP in the lower quartile ranges and those under 75 years of age may have achieved a greater benefit.

The safety profile of vericiguat was consistent with that reported in previous studies. The overall incidences of serious adverse events were similar for the vericiguat (32.8%) and placebo (34.8%) groups. Symptomatic hypotension (9.1% vs 7.9%) and syncope (4.0% vs 3.5%) tended to be more common with vericiguat than placebo, but the differences were not statistically significant. Throughout the VICTORIA study, there were no significant between-group differences for renal adverse events such as hyperkalemia or decreases in eGFR. The vericiguat safety profile was also similar when in combination with other therapies used in heart failure patients.

About Heart Failure With Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF), formerly known as systolic heart failure, is characterized by the compromised ability of the heart to eject blood sufficiently during its contraction phase. In the U.S., 6.5 million people have heart failure, and approximately 40-50% of these patients have HFrEF. Annually, approximately 30% of patients with symptomatic chronic heart failure will experience worsening of the disease, which is marked by progressive symptoms and/or a recent heart failure event. Approximately half of patients with worsening chronic HFrEF are rehospitalized within 30 days of a worsening event, and an estimated one in five patients with worsening chronic HFrEF will die within two years.

About the Worldwide Collaboration Between Bayer and Merck

Since October 2014, Bayer and Merck (known as MSD outside of the United States and Canada) are in a worldwide collaboration in the field of sGC modulators. The collaboration brings together two leading companies that have stated their intent to fully evaluate this therapeutic class in areas of unmet medical need. The vericiguat program is being co-developed by Bayer and Merck.

About Merck

For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

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