Kidney Week

Abstract: TH-PO0817

Renal Impairment Does Not Have a Clinically Meaningful Effect on the Pharmacokinetics of the Oral PCSK9 Inhibitor Enlicitide

Session Information

• Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Johns, Douglas, Merck & Co Inc, Rahway, New Jersey, United States

Douglas Johns, PhD

• Bajwa, Ednan, Merck & Co Inc, Rahway, New Jersey, United States

Ednan Bajwa, MD, MPH

• Banka, Puja, Merck & Co Inc, Rahway, New Jersey, United States

Puja Banka, MD

• Butterfield, Kristin, Merck & Co Inc, Rahway, New Jersey, United States

Kristin Butterfield, MS

• Gheyas, Ferdous, Merck & Co Inc, Rahway, New Jersey, United States

Ferdous Gheyas, PhD

• Skataric, Maja, Merck & Co Inc, Rahway, New Jersey, United States

Maja Skataric, PhD

• Younis, Islam Rasem, Merck & Co Inc, Rahway, New Jersey, United States

Islam Rasem Younis, MSc, PhD

• Zhou, Zexun, Merck & Co Inc, Rahway, New Jersey, United States

Zexun Zhou, PhD

Background

Enlicitide decanoate is a novel, oral macrocyclic peptide proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and the first oral PCSK9 inhibitor to complete phase 3 studies, with robust LDL-C reduction (~60%) in participants with hypercholesteremia. Non-clinical and human ADME study results indicate that enlicitide is primarily eliminated intact through passive renal excretion.

Methods

The effect of renal impairment (RI) on enlicitide pharmacokinetics (PK) was evaluated using data from non-compartmental analysis and an integrated population pharmacokinetics (popPK) analysis using phase 1, 2, and 3 studies. Clinical studies with participants with renal impairment (RI) include: A single-dose 20-mg enlicitide phase 1 study in participants with moderate and severe RI, and participants with end stage renal disease (ESRD) on hemodialysis (HD); A 28-day multiple-dose 20-mg enlicitide once-daily (qd) phase 1 study in participants with severe RI; And phase 2, and phase 3 studies (CoralReef Lipids, and CoralReef HeFH) that included participants with mild and moderate RI.

Results

Following enlicitide 20-mg qd dose, the steady-state enlicitide exposures (AUC_0-24) in phase 3 participants with mild (n=844) and moderate (n=191) RI were 5% and 11% higher, respectively, compared with participants with normal renal function. PopPK analysis predicts that following enlicitide 20-mg qd dose, patients with severe RI may have a ~ 26% higher steady-state enlicitide exposure compared with patients with normal renal function. In the phase 1 single-dose study, enlicitide exposure (AUC_0-inf) was 17% higher in participants with ESRD, compared with healthy participants, when enlicitide was administered before HD.

Conclusion

The increase in enlicitide exposure in participants with RI is not clinically meaningful based on the established safety profile of enlicitide (up to 300-mg single dose and 120-mg qd multiple dose). Therefore, enlicitide can be administered to patients with hypercholesterolemia and RI with no dose adjustment needed.

Acknowledgment

The authors thank the participants and their families and all investigators and site personnel who participated in these studies. The authors would like to thank John Facciponte, PhD, for writing assistance and Sheila Erespe, MS for preparing the abstract for logistical support (both are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA). Medical writing assistance funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

• Commercial Support – Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA