Reassessing Merck’s VERQUVO in Heart Failure: Mixed Trial Results and Strategic Implications for Biopharma Investors

Merck’s VERQUVO (vericiguat) has faced a pivotal moment in its journey to redefine heart failure management. The Phase 3 VICTOR trial, which evaluated the drug in stable chronic heart failure with reduced ejection fraction (HFrEF) patients without recent decompensation, failed to meet its primary endpoint, showing a 18% event rate in the VERQUVO group versus 19.1% in the placebo group (hazard ratio [HR] 0.93; p=0.22) [1]. This outcome initially raised questions about the drug’s long-term efficacy. However, a pre-specified pooled analysis of VICTOR and VICTORIA trial data—spanning 11,155 HFrEF patients—revealed a statistically significant 12% relative risk reduction in the composite endpoint of cardiovascular death or heart failure hospitalization [1]. This finding, consistent with VERQUVO’s approved indication for post-decompensation HFrEF patients, underscores its value in high-risk populations despite the VICTOR setback.

The drug’s safety profile remains a critical pillar of its risk-benefit analysis. Adverse events such as hypotension and anemia were consistent with prior trials, with no new safety signals emerging in the pooled analysis [1]. This consistency reinforces VERQUVO’s role as a complementary therapy in guideline-directed medical therapy (GDMT) regimens, particularly for patients with residual risks despite optimized care. Analysts note that the VICTOR trial’s design—targeting a well-treated, ambulatory cohort with 47.5% of participants having no recent hospitalizations—may have limited its ability to detect efficacy in a lower-risk population [3]. The pooled data, however, suggest that VERQUVO’s benefits are most pronounced in patients with recent decompensation, aligning with its current label and real-world application.

Merck’s broader cardiovascular strategy, however, extends beyond VERQUVO. The company has allocated $3 billion in annual cost savings to R&D, accelerating development of pipeline assets like WINREVAIR™ (sotatercept-csrk) for pulmonary arterial hypertension (PAH) and enlicitide decanoate, an oral PCSK9 inhibitor targeting the $10 billion lipid-lowering market [2]. These investments reflect Merck’s ambition to diversify its post-Keytruda growth, with a focus on high-unmet-need areas. The acquisition of Verona Pharma and Acceleron Pharma for $21.5 billion has further bolstered its cardiopulmonary portfolio, positioning it to compete in niche markets with limited therapeutic options [2].

Strategic agility is evident in Merck’s use of real-world data and innovative trial designs. The 5-STAR analysis of the VICTORIA trial, which stratified patients by biomarkers like GDF-15 and NT-proBNP, revealed a more pronounced treatment effect than the original analysis, suggesting that risk-stratified approaches could enhance vericiguat’s clinical utility [4]. Additionally, Merck’s CADENCE trial of sotatercept in Cpc-PH secondary to heart failure with preserved ejection fraction (HFpEF) highlights its commitment to addressing complex, overlapping cardiovascular conditions [3]. These initiatives align with industry trends emphasizing precision medicine and patient-centric outcomes.

Financial resilience further underpins Merck’s long-term growth potential. A $21 billion investment in U.S. manufacturing and R&D facilities through 2028 ensures operational flexibility amid patent expirations and pricing pressures [2]. Analysts project 16.7% earnings growth for 2025, driven by operational efficiencies and a diversified pipeline [2]. While the VICTOR trial’s mixed results may temper short-term expectations, Merck’s focus on high-impact therapeutic areas—such as PAH and lipid-lowering therapies—positions it to offset near-term challenges and sustain revenue growth.

For biopharma investors, the key takeaway is Merck’s ability to balance scientific innovation with strategic execution. The pooled VICTOR/VICTORIA data reaffirm VERQUVO’s role in HFrEF, while the company’s cardiovascular pipeline and financial discipline signal resilience. As Merck advances WINREVAIR and enlicitide into late-stage trials, its post-Keytruda transformation could redefine its market position, offering investors a compelling long-term opportunity in a therapeutic area with enduring unmet needs.

Source:
[1] Merck Provides New Results for VERQUVO® (vericiguat) in Patients with Chronic Heart Failure and Reduced Ejection Fraction [https://www.merck.com/news/merck-provides-new-results-for-verquvo-vericiguat-in-patients-with-chronic-heart-failure-and-reduced-ejection-fraction/]
[2] Reassessing Merck's Cardiovascular Portfolio [https://www.ainvest.com/news/reassessing-merck-cardiovascular-portfolio-implications-verquvo-mixed-victor-trial-results-pooled-victoria-data-2508/]
[3] Merck Highlights Cardiovascular Innovation at ESC 2025 [https://prismmarketview.com/merck-highlights-cardiovascular-innovation-at-esc-2025-strategic-signals-for-investors/]
[4] Analysis of the VICTORIA Trial Using Novel Prognostic ... [https://www.medrxiv.org/content/10.1101/2025.04.03.25325054v1.full-text]