First Oral PCSK9 Inhibitor Approved for Hypercholesterolemia
On July 15, 2026, the US Food and Drug Administration (FDA) approved Merck’s Lipfendra® (enlicitide) as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults who have hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Lipfendra is a novel macrocyclic peptide that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9) and inhibits its interaction with LDL receptors, resulting in reduced LDL-C levels. Lipfendra is the first FDA-approved oral PCSK9 inhibitor. The recommended dose is 20mg orally once daily. It should be taken once daily on an empty stomach in the morning and swallowed whole. Patients should wait at least 30 minutes after administration before consuming food or beverages other than water, black coffee, or plain tea. The approval occurred sooner than many industry observers anticipated and follows a rapid FDA review under the FDA Commissioner’s National Priority Voucher program. Lipfendra will launch in the coming weeks and Merck plans to introduce a direct-to-consumer program. The wholesale acquisition cost (WAC) is approximately $315 per 30-day supply. Full prescribing information can be found here.
At a Glance
- Brand Drug: Lipfendra® (enlicitide)
- Manufacturer: Merck
- Date Approved: July 15, 2026
- Indication: As an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including HeFH.
- Dosage Forms Available: 20mg film coated tablets
- Launch Date: In the coming weeks
- Estimated Annual Cost: $3,833
- FDA Designation: Priority Review. Commissioner’s National Priority Voucher.
- According to the American Heart Association, one in four US adults, 65 million Americans, have high LDL cholesterol, a major risk factor for atherosclerotic cardiovascular disease (ASCVD), including heart attack and stroke.
- The cholesterol market represents one of the largest primary care therapeutic areas. There are about 50 million Americans on statins; however, almost 70% still have LDL above goal thresholds.
- Standard of care includes statins for primary and secondary prevention. Ezetimibe is often added to statins when LDL goals are not achieved, followed by PCSK9 inhibitors, which until now have been available only as injectable therapies.
- Approval was supported by two phase III trials showing Lipfendra reduced LDL-C by 56% in adults with hypercholesterolemia and 59% in those with HeFH, versus placebo. Treatment also reduced non-high density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB), additional markers associated with ASCVD risk.
- The most common adverse reactions occurring more frequently with treatment than with placebo were dizziness (9% vs. 4%) and diarrhea (7% vs. 2%).
- A cardiovascular outcomes trial (CORALreef Outcomes) is ongoing to evaluate the impact of Lipfendra on cardiovascular morbidity and mortality.
- Lipfendra is the first oral PCSK9 inhibitor approved, providing a daily oral alternative to injectable PCSK9 inhibitors such as Repatha® (evolocumab – Amgen), Praluent® (alirocumab – Regeneron/Sanofi), and Leqvio® (inclisiran – Novartis).
- AstraZeneca is also developing an oral PCSK9 inhibitor, laroprovstat, with approval possible in 2027.