Keverprazan, a novel potassium-competitive acid blocker: Single ascending dose safety, tolerability, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

Zhou, Sufeng; Xie, Lijun; Zhou, Chen; Zhao, Yuqing; Wang, Lu; Ding, Sijia; Chen, Juan; Zhu, Bei; Su, Mei; Shao, Feng

doi:10.1016/j.ejps.2023.106578

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…This head-to-head study therefore demonstrated that the acid suppression effect of Keverprazan at a dose of 20 mg was more potent and stable than 30 mg of Lansoprazole. 74 Tegoprazan was also a novel P-CAB. The pharmacodynamic data showed that the 50, 100, and 200 mg doses of Tegoprazan demonstrated longer HTRs above pH >4 up to 12 h after evening dosing than the Dexlansoprazole group.…”

Section: Discussionmentioning

confidence: 99%

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis

Liu,

Gao,

Hou

2024

Therap Adv Gastroenterol

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Background: Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. Objectives: This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. Design: A systematic review and network meta-analysis. Data sources and methods: Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. Results: In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. Conclusion: This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. Trial registration: The study protocol was registered with INPLASY (registration number INPLASY2023120053).

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Section: Discussionmentioning

confidence: 99%

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis

Liu,

Gao,

Hou

2024

Therap Adv Gastroenterol

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“…Consequently, it also achieves a good acid inhibition effect. A clinical study reported that after a single dose of 20 mg keverprazan, the percentage of time with gastric pH >3, >4, and >5 exceeded 80% for 24 h, and during the night, the percentage of time with gastric pH >3, >4, and >5 exceeded 95% [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis

Ouyang,

Zou,

Cheng

et al. 2024

Pharmaceuticals

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Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without Helicobacter pylori (H. pylori) infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and H. pylori eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60–2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11–4.42). Subgroup analysis on patients with H. pylori-positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with H. pylori-positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.

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Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments

Scarpignato,

Hunt

2024

Curr Gastroenterol Rep

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Purpose of the Review Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice. Recent Findings Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Summary Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that—in the above two clinical indications—P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

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Keverprazan, a novel potassium-competitive acid blocker: Single ascending dose safety, tolerability, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

Cited by 5 publications

References 33 publications

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis

Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis

Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments

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