FDA Approves Merck Oral Pill for High Cholesterol

The FDA approval of Merck's Lipfendra, the first oral PCSK9 inhibitor for hypercholesterolemia, expands treatment options beyond injectable biologics for patients who do not reach LDL cholesterol targets on statins alone. This development stand to eventually benefit Mexican patients, as cardiovascular disease remains a leading cause of mortality in the country.   

The US Food and Drug Administration (FDA) approved Lipfendra, an oral pill from Merck designed to lower cholesterol, marking the first tablet version of a drug class previously available only through injections. The approval could widen access to treatment for patients with persistent cardiac risk.

Lipfendra, also known as enlicitide, targets a protein called PCSK9, whose elevated levels contribute to higher cholesterol and cardiovascular disease. Brian Foard, Executive Vice President, Merck, says the company plans to position the pill as a complementary treatment for patients already on cholesterol-lowering therapies such as statins. "Seventy percent of patients treated with those therapies still fail to reach the goals recommended by guidelines. We believe this is where the opportunity lies," says Foard. 

The approval addresses a treatment gap that reaches far beyond the US market. High LDL cholesterol, commonly known as bad cholesterol, drives the buildup of arterial plaque and remains a leading contributor to heart attacks and strokes worldwide. According to the American Heart Association, roughly one in four adults in the US has elevated LDL cholesterol levels, a proportion that reflects a broader global pattern of underdiagnosed and undertreated dyslipidemia. 

Cardiovascular disease follows a similar trajectory in Mexico, where pharmaceutical companies are already expanding their cardiometabolic pipelines to meet rising local demand. Bristol Myers Squibb (BMS), for example, is preparing to launch a treatment for a complex inherited heart condition in Mexico this year, citing a growing base of specialists and patients equipped to diagnose and manage such disorders, MBN reported. Obesity, a major risk factor for elevated cholesterol and cardiovascular disease, affects more than one-third of Mexican adults.

Lipfendra is indicated to treat patients with hypercholesterolemia, including those with hereditary forms of the condition, as an add-on to diet and exercise. The medication will be marketed at a list price of US$10.50 per day, or approximately US$315 per month, and Merck says it will become available within weeks of the approval.  

The company built its case on two Phase 3 trials involving thousands of patients with hypercholesterolemia and elevated cardiovascular risk. In one trial, patients taking the pill saw LDL-C fall more than 55% after six months of treatment; in the second, focused on patients with hereditary high cholesterol, the reduction reached 59% compared with a placebo group, the company reported.

Until now, drugs that block PCSK9 have been sold exclusively as injectables, led by established biologics from other pharmaceutical companies that have faced adoption barriers tied to high prices, insurance restrictions, and limited prescribing by doctors. Side effects observed during trials, including dizziness and diarrhea, occurred at similar rates between patients taking Lipfendra and those receiving a placebo, according to Merck. The reduction in LDL-C achieved with the pill matched the efficacy previously reported for injectable PCSK9 therapies, positioning it as a direct alternative rather than a secondary option for prescribers.

The approval also lands as Merck works to diversify its cardiometabolic portfolio ahead of upcoming patent expirations for other flagship products, and as competing pharmaceutical companies pursue their own oral candidates targeting cholesterol and related lipid disorders. 

For health systems in Mexico and other markets grappling with rising cardiovascular mortality, an oral alternative could lower barriers tied to needle aversion, administration logistics and specialist referrals that have limited the reach of injectable PCSK9 inhibitors. Genetic research from Mexico's National Institute of Genomic Medicine (INMEGEN) has also linked hereditary variants to elevated obesity and cardiovascular risk among the Mexican population, reinforcing the relevance of expanding treatment options tailored to patients who do not respond adequately to statins alone. Whether Lipfendra reaches Mexico, and under what regulatory timeline, will depend on future filings with Mexican health authorities, which Merck has not yet detailed.