Is Merck building the next great cardiometabolic franchise? A closer look at WINREVAIR, enlicitide and Ohtuvayre

Merck & Co., Inc. (NYSE: MRK) appears to be engineering its next big franchise—this time not in oncology, but in cardiometabolic and cardio-pulmonary medicine. Following its Q3 2025 earnings beat and guidance upgrade, the pharmaceutical major has spotlighted three assets that could reshape its long-term growth profile: WINREVAIR (sotatercept-csrk), its approved therapy for pulmonary arterial hypertension; enlicitide, a Phase 3-stage oral PCSK9 inhibitor for cholesterol management; and Ohtuvayre (ensifentrine), a novel inhaled COPD treatment acquired through its $10 billion buyout of Verona Pharma. Each of these drugs targets a distinct but often overlapping patient population, and taken together, they form the backbone of Merck & Co., Inc.’s evolving cardiometabolic franchise.

This strategic pivot comes at a time when the company faces patent cliffs and growing price pressure in its legacy oncology business. While Keytruda remains dominant, the need for diversification is now urgent. Cardiovascular and respiratory disease offer exactly the kind of broad, long-duration markets that can support commercial momentum through the 2030s. The company’s cardiometabolic ambitions are increasingly central to how investors model its future—especially as WINREVAIR ramps commercially and enlicitide nears pivotal data readouts.

Why are WINREVAIR, enlicitide, and Ohtuvayre so important to Merck’s post-oncology growth strategy?

The launch trajectory of WINREVAIR underscores Merck & Co., Inc.’s ability to successfully bring first-in-class therapies to market in underpenetrated disease areas. Approved by the U.S. Food and Drug Administration in March 2024 for pulmonary arterial hypertension (WHO Group 1), WINREVAIR has already generated $360 million in global revenue in Q3 2025 alone. Analysts interpret this early traction as validation that Merck & Co., Inc. can execute a specialty launch outside of oncology, in a disease space where survival and quality-of-life remain significant unmet needs.

Meanwhile, enlicitide represents a potentially transformative asset in lipid-lowering therapy. As a once-weekly oral PCSK9 inhibitor currently in Phase 3 trials (CORALreef Lipids and HeFH studies), it targets hypercholesterolemia in both broad and genetic patient groups. The forthcoming late-stage data at the American Heart Association’s 2025 Scientific Sessions could mark a turning point. If enlicitide delivers, it could become the first oral therapy in a category dominated by subcutaneous biologics, and challenge both market incumbents and emerging oral small molecules. The convenience and scalability of oral delivery may unlock significantly higher patient adherence, driving long-term value across cardiology practices globally.

Ohtuvayre, acquired through Merck & Co., Inc.’s July 2025 acquisition of Verona Pharma, completes the current three-pronged cardiometabolic play. Approved by the U.S. Food and Drug Administration in June 2024, Ohtuvayre is the first new inhaled COPD mechanism in over 20 years. Its dual inhibition of PDE3 and PDE4 offers both bronchodilation and anti-inflammatory benefits. Market watchers have flagged Ohtuvayre as a meaningful addition to Merck & Co., Inc.’s respiratory pipeline, particularly because COPD frequently co-exists with cardiovascular disease. This comorbidity positioning may become a key differentiator as payers and physicians look for holistic treatment approaches.

How is the cardiometabolic strategy aligning with broader market dynamics and investor expectations?

Cardiovascular disease continues to be the leading cause of mortality worldwide. Atherosclerotic cardiovascular disease accounts for the majority of those deaths, while COPD is one of the most burdensome chronic conditions globally. Merck & Co., Inc. is targeting both with assets that offer mechanistic innovation and commercial differentiation. Analysts and institutional investors now view the company’s cardiometabolic pivot as not only necessary, but strategically compelling.

By building a diversified pipeline across both rare and prevalent indications—ranging from pulmonary hypertension to cholesterol to respiratory disease—Merck & Co., Inc. is positioning itself to de-risk its revenue profile and enter high-burden therapeutic areas with strong payer interest. WINREVAIR, enlicitide, and Ohtuvayre each bring unique pharmacologic profiles, enabling the company to address cardiovascular and respiratory disease from multiple clinical angles. Importantly, the cardiometabolic strategy is not just pipeline-driven but revenue-generating already, which gives the company real-time feedback on market acceptance and pricing dynamics.

The acquisition of Verona Pharma, while costly, was broadly seen by investors as a pre-emptive response to patent expirations in oncology. It also deepens Merck & Co., Inc.’s bench in a category where innovation had long stagnated. By combining organic pipeline growth with bolt-on acquisitions, the company is signalling that it intends to compete in cardiometabolic disease at scale—not just as a sideline to oncology.

What are the competitive risks Merck must navigate to establish a dominant cardiometabolic franchise by 2030?

Merck & Co., Inc.’s cardiometabolic strategy, while promising, is not without risk. Competitive intensity is high across all three therapeutic areas. In lipid management, enlicitide must not only show non-inferiority or superiority to existing PCSK9 inhibitors, but also prove cost-effective and convenient enough to change prescribing behavior. Moreover, it may face competition from other oral therapies already in development.

In COPD, Ohtuvayre will need to gain traction in a crowded inhaled therapy market that includes generics, combination inhalers, and biologics. While the dual PDE mechanism is novel, formulary access and real-world effectiveness will determine whether it becomes a standard of care. Furthermore, the scale and logistics of inhaled drug manufacturing and distribution introduce operational complexity that may pressure margins in the early ramp-up phase.

WINREVAIR’s growth trajectory is currently strong, but it operates in a highly specialized market. Expansion into broader pulmonary hypertension categories, such as PH associated with heart failure with preserved ejection fraction, will be critical for its long-term commercial relevance. Regulatory risk also remains a factor across the pipeline. Positive data readouts are never guaranteed, and even approved drugs can see shifts in guideline positioning based on new evidence or safety signals.

Integration risk also looms. The Verona Pharma acquisition is expected to be dilutive to earnings per share by approximately $0.16 in the first year, which could test investor patience if topline growth from Ohtuvayre takes time to materialize.

What pipeline progress and regulatory wins shaped sentiment during the quarter?

Investor confidence in the cardiometabolic franchise was buoyed by the continued ramp-up of WINREVAIR, with new patient starts accelerating and international markets opening up. Management noted strong demand in both community and specialty settings, as physicians become more comfortable with the drug’s safety profile and long-term data.

The enlicitide program is nearing a key inflection point, with pivotal data expected to be presented in November 2025. Merck & Co., Inc. has already hinted that enrollment targets were met ahead of schedule, suggesting clinical operations have been smooth. The company’s ability to execute on Phase 3 studies at this scale, and translate that into regulatory filings by 2026, could define its leadership in the next era of cholesterol-lowering therapies.

Ohtuvayre, although a recent addition, has also made progress. In the weeks following the Verona Pharma acquisition, Merck & Co., Inc. began working on international rollout plans and guideline inclusion efforts. These steps suggest that the company is prioritizing rapid scale-up, rather than slow absorption into the broader portfolio.

How does Merck’s revised 2025 guidance shape investor positioning?

Merck & Co., Inc. raised its full-year 2025 guidance following strong Q3 performance, driven in part by contributions from WINREVAIR and vaccine revenue. The revised outlook includes anticipated near-term dilution from the Verona Pharma acquisition, but management expressed confidence that the long-term accretion will outweigh early impact.

For institutional investors, this guidance revision serves as both a reassurance and a challenge. On one hand, it signals that Merck & Co., Inc. is generating new revenue streams even as older assets face headwinds. On the other, it forces portfolio managers to re-evaluate the balance between near-term earnings drag and long-term franchise value creation.

Analysts are split between those who view the cardiometabolic strategy as a necessary hedge and those who see it as the company’s next growth pillar. Either way, it is now central to the company’s valuation model. Investor sentiment has skewed more positively since the Verona Pharma acquisition, with many framing it as a signal that Merck & Co., Inc. will continue to make bold bets beyond oncology.

What should investors watch ahead of regulatory and clinical catalysts in late 2025 and 2026?

All eyes are now on the November 2025 AHA Scientific Sessions, where enlicitide Phase 3 data is expected. A positive readout could reposition Merck & Co., Inc. at the center of the PCSK9 conversation, particularly if the therapy shows robust LDL-C reduction and safety with oral convenience.

WINREVAIR label expansion studies could open up new markets, particularly if data supports use in broader pulmonary hypertension populations or heart failure with preserved ejection fraction. The extent to which regulators, payers and guidelines align on these expansions will directly impact revenue potential into 2026 and beyond.

For Ohtuvayre, key milestones include formulary coverage decisions, global approvals, and real-world outcomes data to support differentiation. Post-approval surveillance and health-economic studies will be critical in building a case for long-term value in a notoriously cost-sensitive market.

In the aggregate, Merck & Co., Inc.’s cardiometabolic franchise may not yet rival the scale of its oncology engine, but it is clearly more than a side project. It represents the company’s most deliberate effort to shape its post-Keytruda era. Whether it becomes the “next great” franchise will depend not just on molecules, but on execution, market shaping, and the company’s ability to lead across specialties it historically played in only peripherally.