PCSK9 inhibitors are some of the most effective LDL-lowering drugs out there, but they’ve all required injection, and some even refrigeration. That just changed, however, with the FDA’s approval of Merck’s Lipfendra (enlicitide), the first ever oral PCSK9i.
- Despite their overall efficacy, PCSK9is have struggled to gain widespread adoption, in some cases due to cost, and in others, payor logistics and convenience.
- Lipfendra comes as a once daily 20mg tablet, making it a convenient alternative to injectables that need dosing every 2-4 weeks or every three months by a professional.
- The approval comes with indications for adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH).
Budding from the CORALreef trial series, including the Lipids and HeFH readouts, Lipfendra’s approval rests on a solid body of data that shows its robust LDL-C reduction ability.
- In CORALreef Lipids, LDL-C fell 57.1% in patients on Lipfendra versus a 3.0% increase with placebo at 24 weeks.
- That’s an adjusted between-group difference of 55.8%.
- Meanwhile, In CORALreef HeFH, the between-group LDL reduction was 59.4%.
- Both studies supported Lipfendra’s safety, though the HeFH group did face numerically higher but non-significant rates of diarrhea (7% vs. 2%) and dizziness (9% vs. 4%).
But a key piece of evidence is still missing. The trials to date establish Lipfendra’s LDL-lowering abilities, not cardiovascular event reduction.
- We still have to wait for the CORALreef Outcomes trial, to know whether Lipfendra actually reduces heart attacks and strokes.
That distinction is important, because it’s what’s actually going to move the needle for Merck as being seen as the go-to for most patients rather than an oral alternative.
- For example, the GLP-1 race taught us that while oral GLP-1s are more convenient, in many cases, some patients prefer the weekly injectables due to better results.
- That said, one study found that people are ambivalent about injections versus pills for their drug regimen.
And of course, pricing, insurance coverage, and payor opinions will factor heavily into whether or not a daily-oral formulation overtakes injectables.
The Takeaway
Being the first to an oral formulation can be its own way to win, and Merck achieved just that with Lipfendra’s approval. Now we just need the data from CORALreef Outcomes to know if it’s as good as its injectable peers.
