Merck’s Enlicitide: A Paradigm Shift in Lipid Management and the $40B Market Opportunity

Merck’s investigational oral PCSK9 inhibitor, enlicitide decanoate, has emerged as a transformative candidate in the $40 billion lipid management market, with three successful Phase 3 trials demonstrating its potential to redefine cholesterol-lowering therapy. The CORALreef HeFH, CORALreef AddOn, and CORALreef Lipids studies collectively showed statistically significant and clinically meaningful reductions in LDL-C, non-HDL-C, apolipoprotein B, and lipoprotein(a) [1]. These results, achieved at Week 24, were accompanied by a favorable safety profile, with adverse event rates comparable to placebo [2]. If approved, enlicitide could become the first oral PCSK9 inhibitor, addressing critical gaps in current treatment paradigms dominated by injectable therapies like Amgen’s Repatha and Novartis’ Leqvio [3].

The lipid management sector is at an inflection point. While statins remain the cornerstone of therapy, they fail to achieve LDL-C targets in high-risk patients, particularly those with familial hypercholesterolemia (FH) or statin intolerance [4]. This unmet need has fueled the rise of PCSK9 inhibitors, a class projected to grow from $2.91 billion in 2025 to $12.4 billion by 2032, driven by a 21.2% CAGR [5]. Enlicitide’s oral formulation directly addresses logistical and compliance barriers associated with injectables, offering a daily pill that could expand access in both developed and emerging markets [6].

Competitive dynamics further underscore enlicitide’s disruptive potential. AstraZeneca’s AZD0780, another oral PCSK9 inhibitor, demonstrated a 50.7% LDL-C reduction in combination with statins, but enlicitide’s broader lipid-lowering effects (including Lp(a) reduction) position it as a more comprehensive solution [7]. Meanwhile, siRNA-based therapies like inclisiran (Pfizer’s Leqvio) require biannual injections, leaving a niche for daily oral alternatives [8]. Merck’s pipeline, combined with its regulatory engagement, suggests a strategic push to capture market share ahead of competitors like LIB Therapeutics, whose once-monthly injectable LIB003 is still in late-stage trials [9].

Key adoption drivers include the growing prevalence of hyperlipidemia—projected to affect over 1.2 billion people globally by 2030—and the increasing emphasis on LDL-C as a cardiovascular risk factor [10]. Enlicitide’s ability to lower LDL-C by up to 50% in Phase 3 trials [11], coupled with its macrocyclic peptide mechanism, could also open avenues for combination therapies and expanded indications, such as non-alcoholic fatty liver disease (NAFLD) [12].

However, challenges remain. High pricing relative to generic statins and the need for robust post-marketing data on cardiovascular outcomes could slow adoption. Regulatory hurdles, though, appear manageable given the drug’s consistent safety profile across trials [13]. Merck’s proactive engagement with regulators and plans to present data at scientific congresses signal confidence in navigating these hurdles [14].

For investors, enlicitide represents a high-conviction opportunity. With a $40 billion lipid management market and a projected $12.4 billion PCSK9 segment by 2032, Merck’s first-mover advantage in oral PCSK9 inhibition could translate into blockbuster sales. The drug’s potential to improve adherence, reduce healthcare costs, and address unmet needs in FH and statin-intolerant patients aligns with broader industry trends toward patient-centric care [15].

Source:
[1] Merck's Investigational Oral PCSK9 Inhibitor Enlicitide Decanoate Met All Primary and Key Secondary Endpoints in Adults with Hypercholesterolemia in Pivotal CORALreef Lipids Study [https://www.merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/]
[2] Merck Announces Positive Topline Results From the First Two Phase 3 CORALreef Trials Evaluating Enlicitide Decanoate for the Treatment of Adults with Hyperlipidemia [https://www.merck.com/news/merck-announces-positive-topline-results-from-the-first-two-phase-3-coralreef-trials-evaluating-enlicitide-decanoate-for-the-treatment-of-adults-with-hyperlipidemia/]
[3] PCSK9 Inhibitors Market Outlook 2034 – Clinical Trials [https://www.barchart.com/story/news/34297655/pcsk9-inhibitors-market-outlook-2034-clinical-trials-market-size-medication-prevalence-companies-by-delveinsight]
[4] Merck's oral PCSK9 makes waves with 3rd phase 3 win [https://www.fiercebiotech.com/biotech/merck-dives-regulatory-talks-after-oral-pcsk9-surfaces-third-phase-3-win]
[5] PCSK9 Inhibitors Market Report | Global Forecast From ... [https://dataintelo.com/report/global-pcsk9-inhibitors-market]
[6] Merck's Investigational Oral PCSK9 Inhibitor Enlicitide Demonstrates Statistically Significant and Clinically Meaningful LDL-C Reductions in Phase 3 Trial [https://www.merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/]
[7] PCSK9 Inhibitors Market Anticipate to Accelerate in the Coming 10 Years Owing to the Increasing Demand for Innovative Cholesterol Lowering Drugs DelveInsight [https://aqurbiosciences.com/2025/02/18/pcsk9-inhibitors-market-anticipate-to-accelerate-in-the-coming-10-years-owing-to-the-increasing-demand-for-innovative-cholesterol-lowering-drugs-delveinsight/]
[8] PCSK9 Inhibitors Market Landscape: Clinical Pipeline [https://www.theglobeandmail.com/investing/markets/markets-news/GetNews/34316838/pcsk9-inhibitors-market-landscape-clinical-pipeline-competitive-strategies-and-growth-drivers-analysis-by-delveinsight-astrazeneca-amgen-regeneron-sanofi-novartis-merck-lib-therapeutics/]
[9] Merck & Co.'s oral PCSK9 contender clears third late-stage trial [https://firstwordpharma.com/story/5993725]
[10] a bibliometric and visual analysis spanning 2007 to 2023 [https://pmc.ncbi.nlm.nih.gov/articles/PMC11621103/]
[11] Merck reports positive Phase III results for oral PCSK9 inhibitor [https://druganddeviceworld.com/2025/06/10/merck-reports-positive-phase-iii-results-for-oral-pcsk9-inhibitor/]
[12] PCSK9 Inhibitors Market Outlook 2034 – Clinical Trials [https://www.barchart.com/story/news/34297655/pcsk9-inhibitors-market-outlook-2034-clinical-trials-market-size-medication-prevalence-companies-by-delveinsight]
[13] Merck's Investigational Oral PCSK9 Inhibitor Enlicitide..., [https://www.merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/]
[14] Merck's oral PCSK9 makes waves with 3rd phase 3 win [https://www.fiercebiotech.com/biotech/merck-dives-regulatory-talks-after-oral-pcsk9-surfaces-third-phase-3-win]
[15] Merck's (MRK) New Therapy Shows Promise in Cholesterol Treatment [https://www.gurufocus.com/news/3089918/mercks-mrk-new-therapy-shows-promise-in-cholesterol-treatment]