Potassium-competitive Acid Blocker Research Articles

Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates.

Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H2RAs, PPIs and P-CABs. By literature search, we identified studies of H2RAs, PPIs or P-CABs that reported mean pH >4 HTRs at steady state (days 5-8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non-linear, mixed-effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P-CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P-CABs, 17.3% for PPIs and 0% for H2RAs. P-CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.

Efficacy of Potassium-competitive Acid Blockers versus Proton Pump Inhibitors in First- and Second-line Eradication Regimens for Helicobacter pylori in Egyptian Patients

Efficacy of Potassium-competitive Acid Blockers versus Proton Pump Inhibitors in First- and Second-line Eradication Regimens for <i>Helicobacter pylori</i> in Egyptian Patients

Vonoprazan vs. Proton Pump Inhibitors for Treatment and Prevention of Gastric and/or Duodenal Ulcers: A Systematic Review with Meta-Analysis.

Although Vonoprazan, a potassium-competitive acid blocker, is superior to proton pump inhibitors (PPIs) in treating Helicobacter pylori and erosive esophagitis, its efficacy for treating gastric and/or duodenal ulcers remains controversial. This meta-analysis summarizes the efficacy and safety of Vonoprazan vs. PPI for treating and preventing gastric and/or duodenal ulcers. Only randomized controlled trials randomizing gastric and/or duodenal ulcer patients, regardless of etiology, into Vonoprazan or any PPI and indexed in Embase, Medline, and CENTRAL until March 2, 2024 were searched. Primary outcomes were ulcer healing rates at Weeks 2, 4, 6, and 8 and recurrence rates at Week 24. Other outcomes included shrinkage rates, any adverse events (AEs), serious AEs (SAEs), and risks of delayed bleeding and perforation. The overall risk ratio (RR) and mean difference were pooled using the random-effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) Tool. Fifteen studies comprising 43 reports were included in the analysis. Healing rates of gastric and/or duodenal ulcers were similar in both Vonoprazan and PPI groups at all weeks (Week 2 RR 1.02 [95%CI 0.89-1.16]; Week 4 0.99 [95% CI 0.95-1.04]; Week 6 1.00 [95% CI 0.96-1.03]; Week 8 0.99 [95% CI 0.95-1.03]). The recurrence prevention of peptic ulcers was not different in Vonoprazan 10mg (RR 0.48; 95% CI 0.18-1.27) or 20mg (0.60; 95% CI 0.28-1.30) to PPI. Shrinkage rates, any AEs, SAEs, and risks of delayed bleeding and perforation were similar in both groups. Vonoprazan is not significantly better than PPI in treating and preventing gastric and/or duodenal ulcers.

Population pharmacokinetic analysis of zastaprazan (JP-1366), a novel potassium-competitive acid blocker, in patients and healthy volunteers.

Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. We aimed to establish a population pharmacokinetic (PK) model of zastaprazan, thereby characterizing the PK of zastaprazan in patients with gastroesophageal reflux disease (GERD) as well as evaluating the impact of various covariates, including CYP2C19 phenotypes, on zastaprazan PK. This population PK analysis included zastaprazan plasma concentration-time data from 92 patients with erosive GERD and 68 healthy volunteers without any gastrointestinal disorders and was performed using nonlinear mixed-effect modeling. Simulations were conducted to predict zastaprazan PK under various dosing regimens in patients with GERD. The plasma PK of zastaprazan was adequately described by a two-compartment model with Erlang-type absorption (six sequential compartments) and first-order elimination. CYP2C19 phenotypes had no significant effect on zastaprazan PK. The disease status was identified as a significant covariate on apparent clearance of zastaprazan, showing lower values in patients with GERD compared to healthy volunteers. However, the model-based simulation indicated that the impact of disease status on zastaprazan exposure was not clinically meaningful. Overall, the current population PK model successfully characterized the observed zastaprazan PK in both patients with GERD and healthy volunteers.

404. REAL-WORLD TREATMENT PATTERN OF EOSINOPHILIC ESOPHAGITIS IN JAPAN

Abstract Background Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration in the esophageal epithelium that causes esophageal dysfunction-related symptoms. The treatment for EoE includes acid suppressants (proton pump inhibitors (PPIs) or potassium competitive acid blocker (P-CAB)), topical corticosteroid (TCS), and diet therapy. In addition, biologics (i.e. dupilumab) have been recently approved for EoE in the US. However, the appropriate initial and maintenance therapy for EoE have not been established yet. Therefore, the aim of the study was to investigate the treatment pattern of EoE and its association with fibrostenosis in Japan. Methods We investigated prescription pattern for EoE analyzing an employer-based health insurance claim database from 2005 to 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. The initial treatment of interest for EoE included PPIs, P-CAB, and TCS (swallowed inhaled CS). The initial treatment for EoE was defined as these drugs prescribed within two months from the index date of EoE diagnosis. The discontinuation rates of initial PPIs or P-CAB were analyzed using Kaplan-Meier method. The discontinuation of treatment was defined as no treatment following within 90 days from the prescription of the previous treatment. Results Overall, 984 EoE patients (45 years old [38-52], male 747 [75.9%]) were ultimately analyzed. Most of the initial treatment for EoE was acid suppressants (PPIs [323 54.9%], P-CAB [241, 41%]), followed by TCS (13, 2.2%) and combination therapy of PPIs or P-CAB and TCS (11, 1.9%). PPIs or P-CAB discontinued in approximately 50% and 70% of the cases at approximately 150 days and 720 days respectively from the start of the initial therapy. The switching to the second-line therapy from the initial PPIs or P-CAB rarely happened. During the observation period, no EoE patients developed esophageal stenosis. Conclusion PPIs or P-CAB were most prescribed as the initial treatment for EoE in Japan. In addition, more than half of EoE patients discontinued such initial therapy within 2 years without fibrostenotic complication. These findings indicate that EoE that can respond to initial acid suppressants therapy does not necessarily require the maintenance therapy to prevent esophageal fibrostenosis.

The efficacy of Keverprazan based quadruple therapy for Helicobacter pylori eradication:a phase III, randomized, double-blind, multicenter trial

IntroductionKeverprazan is a novel potassium-competitive acid blocker, whose advantages as a potent acid suppressor in Helicobacter pylori (H. pylori) eradication has not yet been demonstrated. This study aimed to evaluate the efficacy of Keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. MethodsAdult patients with H. pylori infection were enrolled and randomized to take Keverprazan (KEV group) or Esomeprazole (ESO group)-quadruple therapy (regimen contains Keverprazan 20 mg or Esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, bismuth potassium citrate 240 mg) twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. ResultsFull analysis set showed the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for KEV group and ESO group, respectively (difference: 5.29%; 95% CI: -0.55% to 11.18%). Superiority of Keverprazan over Esomeprazole in terms of eradication rate was observed in the per-protocol set (P=0.0382). The eradication rates for patients resistant or not resistant to clarithromycin were both numerically higher in KEV group than ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 96.67 vs. 93.38% for clarithromycin-nonresistance). The incidence of adverse events was similar in KEV and ESO group (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity and leading to no deaths. ConclusionsKeverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy provided effective H. pylori eradication and was non-inferior to Esomeprazole-based regimen.

Optimized reversed phase liquid chromatography methodology for the determination of vonoprazan fumarate impurities: Towards Six Sigma quality standards and sustainability assessment

Vonoprazan fumarate (VPZ), a potent potassium-competitive acid blocker, holds great promise as a therapeutic option for addressing acid-related disorders. This study introduces a refined reversed phase liquid chromatography methodology tailored for the comprehensive analysis of eight related substances, including starting materials, byproducts, and degradants within VPZ. Our approach integrates response surface methodology and tolerance analysis to achieve six sigma quality standards in chromatographic performance. By embedding specifications into the optimization process, we ensure robustness during method development. Chromatographic separation was executed using an XSelect CSH Phenyl-Hexyl column under stepped gradient conditions, employing a mobile phase comprising 0.1 % trifluoroacetic acid aqueous solution and acetonitrile. The flow rate was maintained at 1.3 mL/min, with UV absorbance at 252 nm, and a column temperature set at 25 °C. To evaluate the stability indicating ability of the method, forced degradation studies were conducted. Importantly, identified degradants did not interfere with the accurate quantification of VPZ and its associated impurities. Validation of the method was achieved through accuracy profiles. A greenness assessment was conducted using National Environmental Methods Index (NEMI), carbon footprint analysis, Analytical Greenness Calculator (AGREE), and Complementary Green Analytical Procedure Index (Complex GAPI). Additionally, blueness and whiteness assessments were conducted using the Blue Applicability Grade Index (BAGI) and Red-Green-Blue 12 (RGB 12) algorithms, respectively. The proposed method exhibited a green profile in NEMI and Complex GAPI. The carbon footprint was calculated at 0.055 kg CO2 equivalent per sample. The AGREE score was 0.67, BAGI was 80.0, and the whiteness score from the RGB12 algorithm was 83.5.This methodological framework holds promise for utilization in process development and quality assurance of VPZ in bulk drug manufacturing, particularly in the absence of official monographs within recognized compendia.

Analysis of immune checkpoint inhibitors for advanced non-small cell lung cancer in patients receiving antacids

BackgroundProton pump inhibitors (PPIs) are reported to decrease the efficacy of immune checkpoint inhibitors (ICIs), but there are few reports on the association between ICI efficacy and antacids other than PPIs, and simultaneous examination of the effects of antacids, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) on ICI therapy. MethodsWe conducted a retrospective study of 381 patients with non-small cell lung cancer who received ICI therapy from January 1, 2016 to December 31, 2022. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Antacids included histamine type 2 receptor antagonists (H2RAs), PPIs, and potassium-competitive acid blockers (P-CABs). ResultsAntacids were administered to 218 patients, including 168 with PPIs, 37 with P-CABs, and 13 with H2RAs. Patients with antacids had worse median PFS and OS than those without antacids (PFS, 2.9 vs. 6.2 months; OS, 12.3 vs. 24.0 months), and those with PPIs, P-CABs, or H2RAs had similar results. However, there were no significant differences between patients with and without antacids when stratified by corticosteroid and NSAID use. Multivariate analyses showed that corticosteroids and NSAIDs administered for cancer-associated symptoms were related to poor prognosis, but antacids including PPIs, P-CABs, or H2RAs were not related. ConclusionsAntacids were not related to ICI efficacy when NSAIDs or corticosteroids were taken into consideration. This may be because the most frequent reason for administering NSAIDs and corticosteroids was cancer-associated symptoms, which are a poor prognostic factor, and most of the patients treated with these medications also received antacids.

Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial.

Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1month. Each parameter significantly improved after 4 and 8weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

Vonoprazan as a Long-Term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-Label Study

Background & AimsAcid secretion inhibitors are associated with hypergastrinemia, which can lead to gastric mucosal changes. Potassium-competitive acid blockers, such as vonoprazan, are more potent than proton pump inhibitors, but long-term safety data are lacking. MethodsIn this phase 4, randomized trial, patients with erosive esophagitis (EE) received induction therapy (once-daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once-daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). The primary endpoint was the proportion of patients with malignant epithelial cell alterations, parietal cell hyperplasia, foveolar hyperplasia, enterochromaffin-like (ECL) cell hyperplasia, and G-cell hyperplasia. ResultsOverall, 202/208 patients (vonoprazan n=139; lansoprazole n=69) achieved healed EE and received maintenance therapy. No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was one adenoma in each group. At week 260, more patients taking vonoprazan versus lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%); proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar. Median serum gastrin levels were higher with vonoprazan treatment versus lansoprazole (625 pg/mL vs 200 pg/mL). Incidences of adverse events were comparable for both treatments. ConclusionsThe exploratory VISION study assessed the safety profile of vonoprazan and lansoprazole over 5 years in Japanese patients with healed EE. While gastrin concentration, parietal cell hyperplasia and foveolar hyperplasia were higher in the vonoprazan group, there was no increased risk of malignant epithelial cell alterations and gastric NETs. (ClinicalTrials.gov, NCT02679508.)

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis: A Meta-analysis Based on Randomized Controlled Trials.

This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.

Long-term follow-up of patients developing gastric mucosal lesions after initiating the potassium-competitive acid blocker vonoprazan.

Long-term follow-up of patients developing gastric mucosal lesions after initiating the potassium-competitive acid blocker vonoprazan.

Efficacy and Safety of Potassium-Competitive Acid Blockers vs Proton Pump Inhibitors for Peptic Ulcer Disease or Postprocedural Artificial Ulcers: A Systematic Review and Meta-analysis.

Peptic ulcer disease (PUD) and postprocedural artificial ulcers are common ulcer disease. For them, proton pump inhibitor (PPI) and potassium-competitive acid blocker (P-CAB) are commonly used in clinical practice. PPI requires acid, time, and multiple doses, but P-CAB has fewer limitations. We compared the efficacy, safety, and prevention of PPI and P-CAB in PUD or artificial ulcer. We searched PubMed, ClinicalTrials.gov , Embase, Cochrane Library, and Web of Science databases for all studies. All eligible randomized controlled trials up to August 5, 2023, were included. Healing rates, shrinking rates, treatment-emergent adverse events rates, and recurrence rates were measured. Risk of bias, sensitivity analyses, and heterogeneity were also performed. Twenty researches that were selected from 926 screening studies and in total 6,551 participants were included. The risk ratio (RR) of healing rate with P-CABs vs PPIs of PUD at 4 weeks was RR 1.01 (95% confidence interval 0.98-1.04). In addition, the healing rate distinction of artificial peptic ulcer was RR 1.04 (0.89-1.22), and the shrinking rate was mean difference 0.10 (-1.30-1.51). The result of treatment-emergent adverse event rate of PUD was RR 1.11 (0.91-1.35), and the delayed bleeding rate of artificial ulcer was RR 0.35 (0.16-0.80). The RR for recurrence rate of drug-related ulcers was 0.45 (0.25-0.81). P-CAB is noninferior in healing artificial ulcer and PUD, also the incidence of treatment-emergent adverse events. But, there may be a statistical advantage in holding back delayed bleeding and preventing drug-induced ulcers. More standardized experiments are needed for further applications and more precise conclusions.

A Comprehensive Comparative Study of Potassium-Competitive Acid Blockers Is Necessary.

A Comprehensive Comparative Study of Potassium-Competitive Acid Blockers Is Necessary.

Efficacy of fexuprazan compared with rebamipide in Korean patients with gastritis: A matching-adjusted indirect comparison.

Gastritis is one of the most frequently diagnosed diseases requiring medical treatment in South Korea. Fexuprazan, a novel potassium-competitive acid blocker, has been approved for treating gastritis and erosive esophagitis. Meanwhile, rebamipide is the most commonly used mucoprotective agent for acute and chronic gastritis in real-world settings in South Korea. However, there have been no studies comparing the efficacy of these two drugs yet. To compare the efficacy of fexuprazan with that of rebamipide for acute and chronic gastritis. This was a matching-adjusted indirect comparison. Individual patient data from a phase III study of fexuprazan (10 mg BID) were compared with cumulative data from two matching studies of rebamipide (100 mg TID). Erosion improvement and healing rates were compared between two weeks of fexurapan, two weeks of rebamipide, and four weeks of rebamipide. The two main outcome variables were presented as percentages, and the risk differences (RD) and 95% confidence intervals (CI) were calculated for the relative treatment effects. In the primary analysis, the erosion improvement and healing rates after a two-week treatment with fexuprazan were 64.5% and 53.2%, respectively, while a two-week treatment with rebamipide resulted in erosion improvement and healing rates of 43.6% (RD: 21.0%; 95%CI: 9.6-32.3; P < 0.01) and 35.6% (RD: 17.6%; 95%CI: 6.1-29.2; P = 0.003), respectively. In the additional analysis, the erosion improvement and healing rates for the two-week fexuprazan treatment (64.2% and 51.2%, respectively) were similar to those obtained during a four-week treatment with rebamipide (60.6%; RD: 3.6%; 95%CI: -9.8, 17.0; P = 0.600 and 53.5%; RD: -2.3%; 95%CI: -16.1, 11.5; P = 0.744, respectively). The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the four-week rebamipide treatment for patients with gastritis.

Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis.

Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE). A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points included the healing rate at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) ( P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments, and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the 2 groups ( P = 0.047), but both decreased after treatment. An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Vonoprazan: a promising advancement in proton pump inhibitor therapy

Vonoprazan, a potent potassium-competitive acid blocker (P-CAB), has emerged as a potential therapeutic option for acid-related disorders, particularly gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD). This comprehensive review aims to provide an overview of the efficacy, safety profile, and clinical implications of vonoprazan based on current literature. Efficacy studies have demonstrated vonoprazan's superiority over proton pump inhibitors (PPIs) in achieving effective acid suppression, rapid symptom relief, and promoting mucosal healing in patients with GERD and PUD. Moreover, its long-lasting acid suppression properties offer protection against Helicobacter pylori (H. pylori) infection, presenting it as a potential alternative to traditional triple H. pylori eradication regimens. Safety evaluations reveal a favourable tolerability profile with minimal adverse effects and a lower risk of drug interactions compared to PPIs. However, concerns regarding long-term safety, such as hypomagnesemia and the potential for rebound acid hypersecretion, necessitate further investigation. Additionally, the role of vonoprazan in special populations, such as the elderly and those with renal impairment, warrants exploration. Overall, vonoprazan represents a promising advancement in acid suppression therapy, offering efficacy, safety, and potential advantages over traditional agents.

Zastaprazan: First Approval.

Zastaprazan (JAQBO®) is a next-generation potassium-competitive acid blocker being developed by Onconic Therapeutics, a subsidiary of Jeil Pharmaceutical, for the treatment of acid-related diseases. Zastaprazan binds directly to proton pumps in a competitive manner to reduce gastric acid secretion, allowing for a quick onset of action. On 24 April 2024, zastaprazan received approval in South Korea for the treatment of erosive gastroesophageal reflux disease (GERD). Zastaprazan is also undergoing phaseIII development for the treatment of gastric ulcer and for the prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer. This article summarizes the milestones in the development of zastaprazan leading to this first approval for erosive GERD.

Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.