Merck cholesterol pill matches injectables in landmark trial
Oral PCSK9 inhibitor cuts LDL by 64.6%, potentially disrupting $3bn market dominated by Amgen, Novartis
Merck's experimental oral cholesterol drug achieved efficacy comparable to injectable treatments in a pivotal Phase 3 trial, results that could reshape a multibillion-dollar market currently dominated by biologic therapies from Amgen and Novartis.
The drug, enlicitide decanoate, reduced low-density lipoprotein cholesterol (LDL-C) by 64.6% at eight weeks when added to background statin therapy, matching the performance of injected PCSK9 inhibitors like Amgen's Repatha and Novartis's Leqvio. The findings were presented Monday at the ACC.26 medical conference.
The trial's primary endpoint showed enlicitide significantly outperformed existing oral alternatives: it cut LDL-C by 56.7 percentage points more than bempedoic acid, 36 percentage points more than ezetimibe, and 28.1 percentage points more than the combination of both drugs. The compound demonstrated a clean safety profile with no serious adverse events reported among patients treated with enlicitide.
"This is the first time an oral PCSK9 inhibitor has shown antibody-like LDL-C reduction with a placebo-like safety profile," Merck stated in its press release, noting that 78.2% of patients on enlicitide achieved the goal of at least a 50% LDL-C reduction alongside an LDL-C level below 55 mg/dL.
The results represent a significant advance for patients who struggle to reach cholesterol targets with current therapies. Nearly 70% of people with atherosclerotic cardiovascular disease on lipid-lowering medications fail to achieve guideline-recommended LDL-C levels, Merck said.
Merck shares rose 1.6% in morning trading to $119.62, giving the drugmaker a market capitalization of approximately $296 billion. The stock is up 8.2% year-to-date and trades below analysts' average price target of $128.04, according to market data.
The PCSK9 inhibitor market is valued at roughly $3.2 billion in 2025 and projected to reach $3.9 billion next year, with estimates suggesting it could expand to $7.7 billion by 2030. Amgen's Repatha generated more than $3 billion in sales during 2025, growing 36%, while Novartis's Leqvio reached $335 million in fourth-quarter sales, up 46% year-over-year.
Both injectable therapies require bi-weekly or bi-monthly administration by healthcare providers, creating barriers to widespread adoption. An oral alternative with comparable efficacy could dramatically expand the addressable patient population by eliminating injection-related hesitancy and logistical burdens.
Merck's enlicitide could particularly pressure Amgen, which has relied on Repatha as a key growth driver. Amgen projected total 2026 revenue of $37 billion to $38.4 billion, with Repatha contributing to that growth despite anticipated pricing pressure. The biotechnology company has forecast mid-single-digit price declines for Repatha in 2026.
The oral PCSK9 inhibitor received a regulatory boost in December 2025 when the U.S. FDA selected enlicitide for the Commissioner's National Priority Voucher, a designation that can expedite review timelines for drugs addressing unmet medical needs.
Analysts at Morgan Stanley and Citigroup have previously identified enlicitide as one of Merck's most valuable pipeline assets, with peak sales potential estimated between $2 billion and $4 billion annually depending on pricing and uptake. The drug's ability to compete with injectables on efficacy while offering oral administration could justify premium pricing relative to generic statins but below biologic costs.
The Phase 3 CORALreef AddOn study enrolled adults with hypercholesterolemia who had either experienced major cardiovascular events or were at risk for a first event. All patients were already on statin therapy, reflecting the real-world population most likely to use additional LDL-lowering treatments.
Beyond LDL-C, enlicitide demonstrated significant improvements in other lipid markers: apolipoprotein B fell 54.6%, non-HDL-C declined 58%, and lipoprotein(a) dropped 26.2% from baseline. These secondary endpoints are increasingly recognized as important cardiovascular risk factors.
Merck, which markets the cancer immunotherapy Keytruda and COVID-19 antiviral molnupiravir among its flagship products, has been investing heavily in cardiovascular research. The company faces looming patent expirations for several major products through the late 2020s, making pipeline additions like enlicitide critical to sustaining growth.
The company plans to submit enlicitide for regulatory approval in the second half of 2026, positioning the drug for a potential launch in 2027. If approved, enlicitide would enter a market where both Amgen and Regeneron have invested heavily in patient education programs and reimbursement support to overcome initial access barriers.