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according to investigators.
Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.
“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.
While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.
The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.
The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.
In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).
Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.
The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).
These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.
Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.
“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.
In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.
Proton pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD). One might ask what the reason would be to challenge this giant of the pharmacopeia with another medication for GERD.
In this important study by Laine et al, vonoprazan is expectedly efficacious in treating nonerosive GERD (NERD) but notably less so when compared with the authors’ trial for erosive GERD. This is not surprising owing to the multiple and common acid independent etiologies of NERD, such as esophageal hypersensitivity. The high placebo response supports this. Two notable results, however, merit emphasis in potential advantages over PPIs.
First, vonoprazan is effective at day 1 of therapy by eliminating the need for loading. Second, nocturnal reflux, a purer form of GERD, is better controlled with a morning dose of vonopazan mitigating against nocturnal acid breakthrough and the need for twice-daily dosing with PPIs and/or addition of an H2 antagonist. These results by no means advocate for replacement of PPIs with PCABs, but at least suggest specific populations of GERD patients who may specifically benefit from PCAB use. The study also indirectly emphasizes that careful selection of NERD patients whose GERD symptoms are predominantly caused by increased esophageal acid exposure are the most appropriate candidates. The ultimate answer as to where vonoprazan will be used in our practice is evolving.
David Katzka, MD, is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City. He has received research support from Takeda, Sanofi, and Regeneron. He is also an associate editor for GI & Hepatology News.
Proton pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD). One might ask what the reason would be to challenge this giant of the pharmacopeia with another medication for GERD.
In this important study by Laine et al, vonoprazan is expectedly efficacious in treating nonerosive GERD (NERD) but notably less so when compared with the authors’ trial for erosive GERD. This is not surprising owing to the multiple and common acid independent etiologies of NERD, such as esophageal hypersensitivity. The high placebo response supports this. Two notable results, however, merit emphasis in potential advantages over PPIs.
First, vonoprazan is effective at day 1 of therapy by eliminating the need for loading. Second, nocturnal reflux, a purer form of GERD, is better controlled with a morning dose of vonopazan mitigating against nocturnal acid breakthrough and the need for twice-daily dosing with PPIs and/or addition of an H2 antagonist. These results by no means advocate for replacement of PPIs with PCABs, but at least suggest specific populations of GERD patients who may specifically benefit from PCAB use. The study also indirectly emphasizes that careful selection of NERD patients whose GERD symptoms are predominantly caused by increased esophageal acid exposure are the most appropriate candidates. The ultimate answer as to where vonoprazan will be used in our practice is evolving.
David Katzka, MD, is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City. He has received research support from Takeda, Sanofi, and Regeneron. He is also an associate editor for GI & Hepatology News.
Proton pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD). One might ask what the reason would be to challenge this giant of the pharmacopeia with another medication for GERD.
In this important study by Laine et al, vonoprazan is expectedly efficacious in treating nonerosive GERD (NERD) but notably less so when compared with the authors’ trial for erosive GERD. This is not surprising owing to the multiple and common acid independent etiologies of NERD, such as esophageal hypersensitivity. The high placebo response supports this. Two notable results, however, merit emphasis in potential advantages over PPIs.
First, vonoprazan is effective at day 1 of therapy by eliminating the need for loading. Second, nocturnal reflux, a purer form of GERD, is better controlled with a morning dose of vonopazan mitigating against nocturnal acid breakthrough and the need for twice-daily dosing with PPIs and/or addition of an H2 antagonist. These results by no means advocate for replacement of PPIs with PCABs, but at least suggest specific populations of GERD patients who may specifically benefit from PCAB use. The study also indirectly emphasizes that careful selection of NERD patients whose GERD symptoms are predominantly caused by increased esophageal acid exposure are the most appropriate candidates. The ultimate answer as to where vonoprazan will be used in our practice is evolving.
David Katzka, MD, is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City. He has received research support from Takeda, Sanofi, and Regeneron. He is also an associate editor for GI & Hepatology News.
according to investigators.
Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.
“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.
While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.
The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.
The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.
In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).
Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.
The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).
These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.
Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.
“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.
In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.
according to investigators.
Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.
“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.
While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.
The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.
The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.
In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).
Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.
The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).
These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.
Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.
“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.
In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY