The U.S. Food and Drug Administration (FDA) has approved a new cholesterol-lowering medication, enlicitide, which will be marketed under the brand name Lipfendra. Developed by Merck, the drug is expected to reach the market within weeks and offers a novel oral option for reducing low-density lipoprotein (LDL) cholesterol levels, a key factor in cardiovascular disease risk.

Lipfendra belongs to a class of medications known as PCSK9 inhibitors, which work by blocking a protein that hinders the body’s ability to clear LDL cholesterol from the bloodstream. Until now, all PCSK9 inhibitors required injections and carried a price tag of approximately $500 to $600 per month. Lipfendra, by contrast, is taken orally once daily, ideally in the morning while fasting and with water, black coffee, or plain tea. The list price is set at $315 for a 30-day supply. Its insurance coverage remains uncertain.

Clinical trials indicate that Lipfendra lowers LDL cholesterol levels as effectively as the injectable PCSK9 inhibitors, reducing LDL by 60 to 70 percent. These results place it at the higher end of cholesterol-lowering therapies, surpassing statins—which have been the standard treatment for decades and reduce LDL by 30 to 50 percent—and other oral treatments such as ezetimibe and bempedoic acid, which lower LDL by roughly 20 percent.

Statins are generally prescribed first due to their well-established safety and affordability, with generic options costing between $5 and $25 per month. However, some patients either cannot tolerate statins or do not achieve sufficient cholesterol reduction with these drugs alone, prompting consideration of additional therapies.

Experts note that PCSK9 inhibitors like Lipfendra provide an important option for patients requiring more aggressive LDL lowering. Dr. Erin Michos, associate director of preventive cardiology at Johns Hopkins University School of Medicine, highlighted the increasing emphasis on achieving lower LDL targets, especially in high-risk individuals. The American Heart Association’s recent guidelines recommend specialized LDL goals based on individual risk profiles, with targets for certain high-risk groups set below 55 mg/dL.

Besides lowering LDL, PCSK9 inhibitors have shown the ability to reduce levels of Lipoprotein(a) [Lp(a)], a cholesterol-carrying protein linked to increased cardiovascular risk that statins do not affect. Dr. Corey Bradley, a preventive cardiologist at Columbia University Irving Medical Center, emphasized that Lipfendra and similar drugs can augment existing oral treatments in patients who need more aggressive cholesterol management.

The updated guidelines recommend cholesterol screening for all adults every five years beginning at age 19. They also advise measuring Lp(a) levels at least once in adulthood and highlight the importance of managing cholesterol in those with familial hypercholesterolemia, a genetic condition that causes elevated LDL levels.

While large trials have demonstrated that PCSK9 inhibitors reduce heart attacks, strokes, and cardiovascular deaths by about 20 percent, a major study is underway to confirm whether Lipfendra's oral formulation confers similar long-term cardiovascular benefits.

With the introduction of Lipfendra, clinicians anticipate an expanded arsenal of therapies that could improve adherence and outcomes for patients needing intensive cholesterol control. However, questions remain regarding insurance coverage and real-world accessibility of the new pill relative to existing therapies.