The US Food and Drug Administration has approved enlicitide, the first oral medication that blocks the PCSK9 protein to lower low-density lipoprotein cholesterol. In two phase 3 trials involving 3,207 adults already on lipid-lowering therapy, the once-daily pill reduced LDL levels by 56 to 60 percent when added to statins, an effect comparable to existing injectable PCSK9 inhibitors. The approval, granted to Merck under the brand name Lipfendra, introduces a tablet-based option for adults with heterozygous familial hypercholesterolaemia or established cardiovascular disease who require additional LDL reduction beyond diet and statins.

The drug inhibits PCSK9, a liver protein that normally degrades LDL receptors, thereby allowing the liver to clear more LDL from the bloodstream. The trials, which ran for 24 weeks, showed that patients with cardiovascular disease or high risk achieved a mean LDL reduction of 56 percent, while those with the inherited form saw a 59 percent drop. The safety profile was broadly similar to placebo, with diarrhoea and dizziness the most commonly reported side effects; discontinuation rates due to adverse events were comparable between groups.

Viewed from Buenos Aires, the president of the Argentine Lipid Society, Augusto Lavalle Cobo, described the approval as a key pharmacological advance in cardiovascular prevention, noting that a significant proportion of adults in Argentina maintain elevated cholesterol levels. In the United States, cardiologists unaffiliated with Merck welcomed the pricing. The manufacturer set a list price of $315 for a 30-day supply, well below the $500 to $600 monthly cost of injectable alternatives. Christopher Cannon, a cardiologist at Brigham and Women’s Hospital in Boston, said the lower cost and oral formulation “would make a big difference” compared with injectables, while David Maron, a preventive cardiologist at Stanford, highlighted the potential to reach far more patients. Only about 1 percent of the estimated six million eligible US patients currently use injectable PCSK9 inhibitors, partly because of cost and reluctance to take injections.

A large cardiovascular outcomes trial is under way to determine whether enlicitide also reduces heart attacks, strokes and cardiovascular deaths. Results are expected in 2029. Until then, the approval rests on LDL reduction as a surrogate marker, a standard regulatory pathway for lipid-lowering therapies. Merck’s head of research, Dean Li, expressed confidence that the outcomes data will mirror the 20 percent risk reduction seen with injectable PCSK9 inhibitors, but the definitive evidence remains several years away.