P0981 - A Population Pharmacokinetic Model of Vonoprazan: Evaluating the Effects of Race and Disease Status on Exposure

Carmelo Scarpignato, MD, PhD, PharmD, MPH, FACG¹, Eckhard Leifke, MD², Neila Smith, MD², Darcy J. Mulford, PhD², Gezim Lahu, PhD³, Axel Facius, PhD³, Colin W. Howden, MD, FACG^4
1United Campus of Malta, Msidia, Malta; ²Phathom Pharmaceuticals, Inc., Buffalo Grove, IL; ³thinkQ2 AG, Baar, Zug, Switzerland; ⁴University of Tennessee College of Medicine, Germantown, TN

Introduction: Vonoprazan, a potassium-competitive acid blocker, is under investigation in the US and Europe for the healing of and maintenance of healed erosive esophagitis (EE) and, in combination with antimicrobials, for the eradication of H pylori infection. Here, we report the characterization of vonoprazan population pharmacokinetics (popPK) based on a participant pool from Japanese and European clinical studies in healthy volunteers (HV) and GERD patients, focusing on the effects of race and disease status on vonoprazan exposure.

Methods: The popPK model used pooled participant data from 13 studies (5 Japanese, 8 European) in HVs and 2 studies in GERD patients (1 Japanese, 1 European). The final dataset (n=1156) was tested for accuracy by comparing simulated vs observed PK results from a recent European vonoprazan GERD study (20 mg and 40 mg QD dosing).

Results: In the final model, disease state (HV vs GERD patient), race (Asian vs non-Asian), fed state, gender, baseline body weight (BW), baseline serum creatinine and age were included as covariates. Non-Asian participants had a slower absorption rate (-30.2%) and lower peripheral volume (-12.9%) than Asian participants. GERD patients had significantly lower clearance (-38.1%), lower central volume (-38.0%) and slower rate of absorption (-55%) than HVs. These effects on the disposition of vonoprazan did not result in any meaningful difference in exposure between non-Asians and Asians, and only a small-to-moderate difference in vonoprazan exposure between GERD patients and HVs (Figure 1).

Discussion: The model adequately described vonoprazan PK and the effects of disease state, fed state, gender, age and baseline BW on its disposition; none of these variables had a clinically meaningful impact on vonoprazan exposure that would necessitate dose changes. Race (Asian vs non-Asian) did not affect the exposure of vonoprazan in a clinically meaningful way. Therefore, the large body of pre-existing clinical data related to vonoprazan (exposure/pharmacology) in Asian subjects can be applied to non-Asians.


Figure: Figure 1. Predicted plasma concentration levels over time following oral vonoprazan 20 mg in a) Asian and non-Asian populations and b) healthy volunteers and GERD patients.


*Indicates the reference for the analysis. Ribbons represent the 90% prediction intervals.


Disclosures:
Carmelo Scarpignato: Phathom Pharmaceuticals, Inc. – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Takeda – Speaker's Bureau.
Eckhard Leifke: Phathom Pharmaceuticals, Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Neila Smith: Phathom Pharmaceuticals, Inc. – Employee.
Darcy Mulford indicated no relevant financial relationships.
Gezim Lahu: Arbor Pharmaceuticals – Consultant. Avacta – Consultant. Debiopharm – Consultant. Omeros – Consultant. Sanofi – Consultant. Takeda – Consultant. Vaccibody – Consultant.
Axel Facius: Phathom Pharmaceuticals, Inc. – Consultant.
Colin Howden: Alfasigma – Consultant, Speaker's Bureau. Allakos – Consultant. Alnylam – Speaker's Bureau. Clexio – Consultant. ISOThrive – Consultant. Phathom Pharmaceuticals, Inc. – Advisory Committee/Board Member, Consultant. RedHill Biopharma – Advisory Committee/Board Member, Consultant, Speaker's Bureau.


Carmelo Scarpignato, MD, PhD, PharmD, MPH, FACG¹, Eckhard Leifke, MD², Neila Smith, MD², Darcy J. Mulford, PhD², Gezim Lahu, PhD³, Axel Facius, PhD³, Colin W. Howden, MD, FACG⁴. P0981 - A Population Pharmacokinetic Model of Vonoprazan: Evaluating the Effects of Race and Disease Status on Exposure, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.