On Thursday, the FDA gave Merck & Co Inc. (Merck (MRK)) a big green light for Lipfendra (enlicitide), the first oral PCSK9 inhibitor approved in the U.S. It's a once-daily pill designed to lower low-density lipoprotein cholesterol (LDL-C) — the so-called "bad" cholesterol — in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH), a genetic condition that causes sky-high cholesterol levels.
For context, PCSK9 inhibitors have been around for a while, but they've always been injectable drugs. Lipfendra is the first one you can just swallow. That convenience could be a game-changer for patients who'd rather not deal with needles.
The approval came on the back of two pivotal Phase 3 trials in Merck's CORALreef clinical program, and the numbers are pretty striking.
Phase 3 Trials Show Significant LDL-C Reductions
In the CORALreef Lipids study, patients on Lipfendra saw their LDL-C drop by 56% compared to placebo at week 24. When Merck applied revised post-hoc data handling rules that excluded biologically impossible baseline values, that reduction jumped to 60%. Meanwhile, placebo patients actually saw a 3% increase from baseline. The drug also knocked down other lipid measures tied to cardiovascular risk: non-HDL cholesterol fell by 54%, and apolipoprotein B declined by 50%.
CORALreef HeFH Results Support Approval
The second trial, CORALreef HeFH, focused on adults with the genetic form of high cholesterol. Here, Lipfendra reduced LDL-C by 59% compared to placebo at week 24. From baseline, the treatment group saw a 58% decline, while placebo patients again crept up by 3%. Non-HDL cholesterol dropped 52%, and apolipoprotein B fell 48% relative to placebo.
Merck is also running an ongoing clinical trial to see whether Lipfendra can actually reduce cardiovascular morbidity and mortality — meaning heart attacks, strokes, and deaths. The company was careful to note that it hasn't yet been established whether the drug lowers the risk of cardiovascular events or death. That's a key question, because lowering cholesterol is one thing; preventing bad outcomes is the real prize.
Investors seemed pleased. Merck shares were up 3.61% at $128.07 at the time of publication, trading near their 52-week high of $130.29. The market clearly sees Lipfendra as a valuable addition to Merck's portfolio, especially as the company looks to diversify beyond its blockbuster cancer drug Keytruda.
For patients, the arrival of an oral PCSK9 inhibitor means more options and less hassle. Whether it translates into better long-term outcomes remains to be seen, but the early data is certainly encouraging.
