Merck's oral PCSK9 inhibitor shows 59% LDL-C reduction in HeFH trial

Merck announced compelling Phase 3 results for its investigational once-daily oral PCSK9 inhibitor, enlicitide decanoate, demonstrating a 59.4% reduction in LDL cholesterol at 24 weeks and 61.5% at 52 weeks in adults with heterozygous familial hypercholesterolemia, alongside a comparable safety profile to placebo. If approved, this drug would be the first oral PCSK9 inhibitor, offering a significant alternative to current injectable treatments. This clinical success, coupled with Merck's recent strong Q3 2025 financial performance and strategic pipeline advancements in oncology, underscores the company's robust growth trajectory and strengthens its market position.

Analysis

Merck (MRK) announced compelling Phase 3 CORALreef HeFH trial results for its investigational oral PCSK9 inhibitor, enlicitide decanoate, showing a 59.4% reduction in LDL cholesterol at 24 weeks and 61.5% at 52 weeks versus placebo. This efficacy, with a comparable safety profile, positions enlicitide as a potential first-in-class oral treatment, addressing a significant unmet need and offering an alternative to injectable PCSK9 inhibitors.

These clinical advancements coincide with Merck's robust financial performance, highlighted by stronger-than-expected Q3 2025 results with EPS of $2.58 and revenue of $17.28 billion, both surpassing forecasts. The company maintains a "GREAT" financial health score and an attractive P/E ratio of 11.35 relative to growth prospects, suggesting it is currently undervalued by InvestingPro Fair Value estimates.

Merck is also strategically expanding its portfolio, securing $700 million from Blackstone Life Sciences (BX) for the cancer drug sacituzumab tirumotecan and acquiring full global rights for MK-8690 for $150 million upfront. These proactive investments in R&D and M&A, alongside promising clinical data, reinforce Merck's commitment to diversifying its pipeline and strengthening its long-term competitive position.

Key Decisions for Investors

• Consider Merck (MRK) for long-term portfolio allocation, given its robust clinical pipeline, strong financial performance, and attractive valuation metrics.
• Monitor regulatory approval timelines for enlicitide decanoate, as its potential as the first oral PCSK9 inhibitor could be a significant near-term catalyst for market share expansion.
• Evaluate the long-term revenue potential from new pipeline assets like sacituzumab tirumotecan and MK-8690, considering the royalty structures and milestone payments associated with these strategic deals.