Merck's Enlicitide Decanoate: A Game-Changing Oral PCSK9 Inhibitor with Massive Growth Potential

The global hyperlipidemia market is at a crossroads. With 400 million people worldwide suffering from elevated LDL-cholesterol (LDL-C), current treatments like statins, ezetimibe, and injectable PCSK9 inhibitors have failed to meet the scale of this epidemic. Enter Merck's Enlicitide Decanoate, an oral PCSK9 inhibitor poised to redefine cardiovascular care by addressing the critical limitations of existing therapies. This drug's potential to dominate the $8 billion PCSK9 inhibitor market—and its implications for Merck's long-term growth—make it a compelling investment opportunity.

The Problem with Current PCSK9 Therapies

PCSK9 inhibitors like Amgen's Repatha (evolocumab) and Sanofi's Praluent (alirocumab) are highly effective at lowering LDL-C by up to 60%, but their injectable form has limited adoption. Only 1.5 million patients globally use these drugs, despite 30 million eligible patients in the U.S. alone. The adherence gap stems from inconvenient monthly injections, which contrast sharply with the simplicity of oral therapies. Merck's Enlicitide Decanoate, as an oral macrocyclic peptide, directly tackles this barrier.

Clinical Breakthrough: LDL-C Reduction and Safety

Data from Merck's CORALreef Phase 3 trials (HeFH and AddOn) are compelling:
- LDL-C Reduction: Enlicitide achieved a 66% reduction from baseline in some patients, outperforming ezetimibe and bempedoic acid.
- Safety Profile: No clinically meaningful adverse events were reported, aligning with the benign profile of PCSK9 inhibitors.
- Synergy with Statins: The drug works alongside statins, addressing the 30% of patients who fail to reach LDL-C targets with first-line therapies.

The mechanism is clear: Enlicitide binds to PCSK9, preventing its degradation of LDL receptors. More receptors mean faster LDL-C clearance—a process already validated in injectable PCSK9 inhibitors but now delivered via a daily pill.

Disrupting the Market: Oral vs. Injectable

The oral form's convenience could unlock the PCSK9 market's full potential. Analysts project the global market could grow to $30 billion by 2030 if adherence improves. Enlicitide's direct competitors include:
1. Lerodalcibep (LIB Therapeutics): An oral PCSK9 inhibitor in late-stage trials, but Merck's head start in Phase 3 could secure first-to-market advantage.
2. Ezetimibe (Zetia): A generic option with weaker LDL-C reduction (~20%) and no cardiovascular outcome data.
3. Gene therapies (VERVE-101/102): While innovative, their high cost and one-time use make them niche solutions.

Merck's partnership with Cyprumed to enhance oral peptide delivery adds strategic depth, ensuring Enlicitide's bioavailability remains superior to rivals.

Regulatory Catalysts: NDA Submission and Outcomes Data

While the CORALreef Outcomes trial (TIMI 77) won't conclude until 2029, its primary completion in 2025 for lipid-focused trials (HeFH and AddOn) creates a clear path to approval. Merck is likely to file an NDA by early 2026, leveraging LDL-C reduction data as a surrogate endpoint. Positive results from the 17,000-patient CORALreef program will solidify its position, while the outcomes trial will validate cardiovascular benefit—a critical differentiator for payers.

Investment Thesis: A Multi-Billion Dollar Opportunity

Enlicitide's success hinges on three pillars:
1. Market Need: 30 million U.S. patients and 400 million globally require better LDL-C management.
2. Competitive Edge: Oral delivery could capture 50–70% of the PCSK9 market, generating $2–3 billion in annual sales.
3. Pipeline Synergy: Merck's cardiovascular portfolio (e.g., CVRX's renal denervation tech) reinforces its leadership in ASCVD solutions, which account for 85% of cardiovascular deaths.

Risks include pricing pressure from payers and potential outcomes trial setbacks, but Enlicitide's early data and Merck's execution track record mitigate these concerns.

Conclusion: A Must-Watch Catalyst for Merck Investors

Enlicitide Decanoate isn't just an incremental improvement—it's a paradigm shift in hyperlipidemia treatment. With a clear path to FDA approval and a massive addressable market, this drug could fuel Merck's growth for a decade. Investors should monitor Q2 2026 NDA filing timelines and 2025 Phase 3 lipid data releases as key catalysts. For a company seeking to diversify beyond its diabetes and cancer portfolios, Enlicitide is the next frontier.

Investment Action: Consider adding Merck (MRK) to portfolios with a 12–18-month horizon, targeting a 20–30% upside if Enlicitide gains FDA approval in 2027.

Stay tuned for the next wave in cardiovascular innovation.