Things went well this week for Merck, as on July 16, 2026, it was able to receive FDA approval of its drug LIPFENDRA [enlicitide] 20 mg as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol [LDL-C] in adults with hypercholesterolemia. This drug is a novel macrocyclic peptide that has been approved for these patients. In terms of this big pharma achieving a first, it is the first oral PCSK9 inhibitor that has been approved to reduce LDL-C [bad cholesterol].

What exactly makes this FDA approval of LIPFENDRA for these hypercholesterolemia patients a landmark one? It is because it has been approved specifically as an oral once-daily PCSK9 inhibitor. The point about this is that there have been injectable PCSK9 inhibitors approved to treat these patients.

These would be REPATHA from Amgen and then PRALUENT from Sanofi and Regeneron Pharmaceuticals. The problem initially for these was the high list price, which stunted growth. Even in the face of this problem, both drugs were still able to achieve substantial revenues. Although, this was achieved by cutting prices by as much as 60%.

Still, even with these drugs finding some kind of legs, there was new competition looming. This would be small interfering RNA [siRNA] LEQVIO [inclisiran]. This particular drug, from Novartis, is responsible for targeting the messenger RNA [mRNA] that’s responsible for producing the PCSK9 protein that leads to disease.

What makes this a formidable competing drug to assist patients in lowering their LDL-C who need additional lowering is that it is only given twice yearly as an injectable. The hope for Merck now is that its oral PCSK9 LIPFENDRA pill might be able to do better. Not just on pricing, but also in terms of an easier route of administration as a once-daily oral pill.

Hypercholesterolemia is characterized as high amounts of low-density lipoprotein [LDL-C] or bad cholesterol in the blood. The importance of bringing this down to normal or near normal levels is so that a person can avoid the risk of having a heart attack and/or stroke. Specifically, another problem with hypercholesterolemia is that it can also lead to atherosclerotic cardiovascular disease [ASCVD]. What this entails is cholesterol depositing in artery walls as plaque. In turn, this leads to a narrowing of the arteries and ultimately a heart attack or stroke.

The ability for Merck to file for FDA approval was based on two studies, which were CORALreef Lipids and CORALreef HeFH. In both of these studies, patients treated with LIPFENDRA achieved a statistically significant reduction of LDL-C with placebo-adjusted values of 56% and 59%, respectively

Speaking of CORALreef HeFH, the point of this study was to target what is known as Heterozygous Familial Hypercholesterolemia [HeFH]. It is an inherited genetic disorder from only one parent that causes high levels of bad cholesterol. That’s all it takes for a person to have the inability for their liver to remove LDL-C from the bloodstream. Having said that, LIPFENDRA was also approved for this genetic hypercholesterolemia patient population as well.

The point of this drug is that it is not set to act as a competing drug against statins. Patients are still going to be receiving statins, but it is being added as an additional therapy to help patients achieve guideline LDL-C goals. As a matter of fact, 70% of such cardiovascular patients don’t reach their recommended guideline goal. Analysts believe that peak sales of LIPFENDRA could reach $5 billion.

There might be a way for the company to further prove that such an oral PCSK9 therapy as this might be ideal for helping these hypercholesterolemia patients. Why is that? That’s because it is currently evaluating this drug in the ongoing CORALreef Outcomes trial. The purpose of this study is to see a correlation. That is, if lowering LDL-C ends up resulting in preventing major adverse cardiovascular events [MACE] like a heart attack or stroke.