Pitfalls of Physician-Directed Treatment of Helicobacter pylori: Results from Two Phase 3 Clinical Trials and Real-World Prescribing Data

Abstract

Background: Helicobacter pylori (H. pylori) infects ~ 35% of Americans and can lead to serious sequelae if left untreated. Growing evidence indicates that clarithromycin-based therapies (CBT) are becoming increasingly ineffective for treating H. pylori infection. RHB-105 was approved by the US Food and Drug Administration in 2019 for the treatment of H. pylori infection in adults.

Aims: The primary aim of this study was to assess prescribing patterns and associated cure rates of physician-directed therapy for subjects with persistent H. pylori infection after participation in one of two Phase 3 clinical trials (ERADICATE Hp and ERADICATE Hp2).

Methods: We reviewed study reports to identify specific physician-directed regimens selected for subjects whose H. pylori infection was not eradicated. We also conducted a CYP2C19 genotype analysis of subjects who were prescribed CBT. Finally, we analyzed real-world H. pylori retail prescription data and compared these with to the physician-directed therapies in the clinical trials studies.

Results: Following ERADICATE Hp, CBT was prescribed for 27/31 (87%) subjects achieving a 59.3% cure rate. Following ERADICATE Hp2, CBT was prescribed for 48/94 (51%) subjects achieving a 60.4% cure rate. Rapid CYP2C19 metabolizers (2/11) had a cure rate of 18.2% with CBT. Real-world prescription data from IQVIA showed more than 80% of prescriptions for H. pylori infection were for CBT.

Conclusions: Rates of CBT use persist despite sub-optimal eradication rates. Since RHB-105 does not contain clarithromycin, it can be prescribed first-line without concerns about clarithromycin resistance or CYP2C19 status. NCT03198507 & NCT01980095.

Keywords: CYP2C19; Clarithromycin; Helicobacter pylori; RHB-105; Rifabutin; Stomach; Talicia.

Conflict of interest statement

Dr. CH is a Professor Emeritus, Department of Medicine, University of Tennessee College of Medicine, Memphis, TN. He serves as a consultant to RedHill Biopharma, Phathom, Allakos, Ironwood, EndoStim. Speaker for RedHill Biopharma, Alnylam, Sanofi / Genzyme. Stockholder of Antibe Therapeutics. Dr. WC is a Nostrant Professor of Gastroenterology & Nutrition Sciences, Director of the GI Physiology Laboratory, Director of the Digestive Disorders Nutrition & Lifestyle Program, and Co-Director of the Michigan Bowel Control Program. He serves as a Board Member for the American College of Gastroenterology, International Foundation of GI Disorders, Rome Foundation. He serves as a consultant to Abbvie, Allakos, Alnylam, Arena, Biomerica, Gemelli, Ironwood, Nestle, QOL Medical, Phathom, Progenity, Redhill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant. His research is supported by the NIH, FDA, Biomerica, Commonwealth Diagnostics, QOL Medical, and Salix. He is a shareholder of GI on Demand and Modify Health. Drs. KS and JA are employees of RedHill Biopharma, Inc., Raleigh, NC USA and are stockholders of RedHill Biopharma. Dr. Howden is a consultant for RedHill Biopharma, Phathom Pharmaceuticals, Ironwood, Clexio, Allakos, and Alfasigma. He is a speaker for RedHill Biopharma, Alfasigma, and Alnylam. He owns stock in Antibe Therapeutics. Dr. Sheldon is an employee of RedHill Biopharma, Inc., 8045 Arco Corporate Drive, Suite 200, Raleigh, NC 27617, USA. Dr. Almenoff is an employee of RedHill Biopharma, Inc., 8045 Arco Corporate Drive, Suite 200, Raleigh, NC 27617, USA. Dr. Chey, Board member: American College of Gastroenterology, GI on Demand, International Foundation of Functional GI Disorders, Rome Foundation; Consultant: AbbVie, Alfasigma, Allakos, Alnylam, Bayer, Biomerica, Cosmo, IM Health, Ironwood, QOL Medical, Phathom, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, Vibrant; Grant/Research Support: Bioamerica, Commonwealth Diagnostics International, QOL Medical, Salix; Stock/Stock options: GI on Demand, Modify Health.

© 2021. The Author(s).

Figures

Fig. 1

Percent of total prescribed H. pylori regimens containing clarithromycin by subspecialty