The Efficacy and Safety of Keverprazan, a Novel Potassium-competitive Acid Blocker, in Treating Erosive Oesophagitis

A Phase III, Randomised, Double-blind Multicentre Study

Songfeng Chen; Deliang Liu; Honghui Chen; Aijun Liao; Fangfang Li; Chengxia Liu; Xing Li; Shengbao Li; Yan Zhang; Yang Wang; Min Xia; Qinghong Guo; Xinpu Miao; Zhili Wen; Min Xu; Hekun Yin; Huixin Chen; Minhu Chen; Yinglian Xiao

Disclosures

Aliment Pharmacol Ther. 2022;55(12):1524-1533. 

In This Article

Abstract and Introduction

Abstract

Background: Keverprazan is a novel potassium-competitive acid blocker (P-CAB) with a strong acid-suppressive capacity that may provide clinical benefit in acid-related diseases.

Aims: This study aimed to explore the non-inferior efficacy and safety of keverprazan to lansoprazole in treating erosive oesophagitis (EO).

Methods: This was a phase III, randomised, double-blind multicentre study. Patients were randomised to receive keverprazan 20 mg once daily or lansoprazole 30 mg once daily for 4–8 weeks. EO healing rates and adverse events (AEs) were compared between the keverprazan group and the lansoprazole group.

Results: A total of 238 patients comprised the full analysis set (FAS) while 221 patients comprised the per-protocol set (PPS). For FAS analysis, the EO healing rates at week 8 were 95.8% (114/119) and 89.9% (107/119) for keverprazan and lansoprazole respectively. For PPS analysis, the EO healing rates at week 8 were 99.1% (110/111) and 92.7% (102/110) for keverprazan and lansoprazole respectively. Non-inferiority of keverprazan compared with lansoprazole according to EO healing rates at 8 weeks was demonstrated in both FAS (difference: 5.8% [95% CI: −0.6% to 12.3%]; p = 0.081) and PPS (difference: 6.1% [95% CI: 1.1%–11.2%]; p = 0.018) analysis. Drug-related AEs were reported in 34.5% (41/119) patients of the keverprazan group and 25.2% (30/119) patients of the lansoprazole group with no significant difference (p = 0.156). No severe AE happened in the keverprazan group.

Conclusions: This study demonstrated the non-inferior efficacy of keverprazan to lansoprazole in treating EO. The incidences of drug-related AEs were comparable between keverprazan and lansoprazole.

Introduction

Gastro-oesophageal reflux disease (GORD) is characterised by symptoms such as heartburn and regurgitation caused by the reflux of gastroduodenal contents entering into the oesophagus. Epidemiological studies showed that the prevalence of GORD is up to 13.3% worldwide, covering all age groups and both genders.[1] GORD not only affects patients' quality of life, brings a huge economic burden to social medical resources,[2] but also plays an important role in the occurrence of oesophageal cancer.[3]

Patients with GORD can be classified into having non-erosive gastro-oesophageal reflux disease (NERD), erosive oesophagitis (EO) or Barrett's oesophagus (BO).[4] EO and BO are more severe types of GORD. And EO is graded by the severity of mucosal breaks using the Los Angeles (LA) classification, which ranges from grade A (mild) to grade D (severe) under upper gastrointestinal endoscopy evaluation.[5] Untreated EO might be more likely to develop into oesophageal stricture, oesophageal bleeding or BO, which is the risk factor for oesophageal adenocarcinoma.[6,7]

The treatment of oesophagitis aims to heal mucosa, relieve symptoms, prevent complications and prevent disease progression. The current mainstay therapy of EO is proton pump inhibitor (PPI). However, there was an unmet need for PPI in the treatment of EO. More than 20% of EO patients could not achieve mucosal healing with PPI therapy, implying insufficient acid suppression in the higher grade of EO.[8,9] 3–5 dosages of PPI are needed to reach the maximal efficacy.[10] Furthermore, the efficacy of PPI is dependent on the polymorphism of CYP2C19.[10,11] Finally, PPI can only combine with activated proton pumps, and thus needs to be taken before meals, which may lead to poor patient compliance.[10,11]

Keverprazan (H008; previous name: carenoprazan; online resource Figure S1) is a novel, orally potassium-competitive acid blocker (P-CAB), synthesised by Jiangsu Carephar Pharmaceutical Co. Ltd. in China and is developed to be marketed in both China and outside of China. Unlike PPI, keverprazan is stable in an acid environment, water-soluble and capable to combine with both activated and inactivated proton pump. Preclinical and phase I studies have demonstrated its stability and strong acid-inhibitory ability, as well as its good safety profiles.[12–14] Our phase II study showed that keverprazan was effective and non-inferior to lansoprazole in healing duodenal ulcers at a dose of 20 mg once daily.[15] Whether patients with EO can also benefit from keverprazan remains uncertain.

The current study aimed to explore the efficacy and safety of keverprazan tablets in treating patients with endoscopically confirmed EO.

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