Merck’s Enlicitide Pill Cuts LDL Up to 60% in 2,900‑Patient Trial, Gains FDA Fast‑Track Status
Updated (2 articles)
Landmark NEJM Study Shows Dramatic LDL Reduction The New England Journal of Medicine trial enrolled more than 2,900 high‑risk patients who received daily enlicitide or placebo alongside standard therapy. After six months, participants on enlicitide experienced LDL cholesterol drops of up to 60%, far exceeding reductions from existing oral agents. The effect persisted with only a modest decline over a year and no safety differences emerged between groups [1].
Oral Therapy Matches Injectable PCSK9 Inhibitors, Addresses Statin Gaps Enlicitide lowers LDL through a pathway previously accessible only via injectable PCSK9 inhibitors, offering a convenient oral alternative for patients averse to shots. Researchers highlighted that even maximal statin doses often fail to achieve the guideline‑recommended LDL target of 70 mg/dL in high‑risk individuals, underscoring the need for additional agents like enlicitide [1].
Regulatory Momentum and Ongoing Outcome Trial Highlight Uncertain Clinical Benefits The FDA placed enlicitide in its fast‑track review program, accelerating potential market entry. Merck disclosed that a larger 14,000‑patient trial is underway to determine whether LDL reductions translate into fewer heart attacks, strokes, or deaths, a point emphasized by expert Dr. William Boden who cautioned that outcome data remain pending [1].
Timeline
2021 – A toddler in Nashik receives the first SMA gene‑therapy injection (Zolgensma), marking a milestone that demonstrates gene‑therapy delivery in ordinary neighborhoods and foreshadows later RNA‑based treatments for common diseases [2].
2025 – The U.S. Food and Drug Administration approves six siRNA gene therapies, including Inclisiran for cholesterol, making them available in major hospital pharmacies and extending approval to India, thereby expanding RNA‑based options for patients with severe hyperlipidemia [2].
2025 – Clinical data show Inclisiran lowers LDL cholesterol by roughly 50 % when added to statins, offering a potent alternative for statin‑intolerant patients and reinforcing the shift toward RNA‑mediated lipid control [2].
2025 – Zilebesiran enters trials as a single‑injection siRNA therapy that suppresses hypertension for more than six months, earning the nickname “hypertension vaccine” and illustrating the broader ambition of RNA drugs beyond cholesterol [2].
Feb 2026 – Merck’s oral enlicitide pill cuts LDL cholesterol by up to 60 % after six months in a New England Journal of Medicine trial of over 2,900 high‑risk patients, delivering a reduction greater than any existing pill and persisting with only a slight decline over a year [1].
Feb 2026 – The enlicitide trial reports safety comparable to placebo and demonstrates that the oral agent rivals injectable PCSK9 inhibitors, potentially simplifying treatment for millions who avoid shots [1].
Feb 2026 – The FDA places enlicitide in its fast‑track review program, accelerating the path toward market approval while Merck launches a 14,000‑patient outcome trial to determine whether LDL reductions translate into fewer heart attacks, strokes, or deaths, as experts caution that outcome data remain pending [1].
Feb 2026 – Dr. William Boden calls the LDL‑lowering results “compelling” but warns that the study has yet to prove reductions in heart attacks, strokes, or mortality, underscoring the need for the larger outcome study [1].