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A look at the data behind the FDA approval
Vonoprazan, a potassium-competitive acid blocker, appears to be superior to standard proton pump inhibitor–based therapy in clarithromycin-resistant Helicobacter pylori strains, as well as noninferior to standard care in nonresistant infections, according to a recent study that supported a Food and Drug Administration approval of vonoprazan dual and triple therapies in May 2022.
For decades, H. pylori has been mostly treated by proton pump inhibitor–based triple therapy, which includes a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. However, eradication rates have dropped below 80% in the United States and Europe, according to the authors, mainly because of rising rates of clarithromycin resistance.
Since H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma, better eradication methods should be highlighted, researchers led by William Chey, MD, professor of medicine and director of the GI Physiology Laboratory at Michigan Medicine in Ann Arbor, wrote in Gastroenterology.
In a multicenter, randomized, controlled, phase 3 trial, the research team studied 1,046 treatment-naive adults with H. pylori infection at 103 sites in the U.S., the U.K., Bulgaria, the Czech Republic, Hungary, and Poland between December 2019 and January 2021.
The patients were randomized to receive open-label vonoprazan dual therapy or a double-blind triple therapy twice a day for 14 days. The vonoprazan dual therapy consisted of 20 mg of vonoprazan twice daily and 1 gram of amoxicillin three times per day. The triple therapy consisted of 20 mg of vonoprazan or 30 mg of lansoprazole (standard care), each given with 1 gram of amoxicillin and 500 mg of clarithromycin.
The primary outcome assessed noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains, with a noninferiority margin of 10%. Secondary outcomes assessed the superiority in eradication rates in clarithromycin-resistant infections, as well as in all patients.
Eradication rates for nonresistant strains were 84.7% for vonoprazan triple therapy and 78.5% for vonoprazan dual therapy, compared with 78.8% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered noninferior to standard therapy.
The eradication rates in clarithromycin-resistant infections were 65.8% for vonoprazan triple therapy and 69.6% in vonoprazan dual therapy, compared with 31.9% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior to standard therapy, with a difference of 33.9 percentage points for triple therapy and 37.7 percentage points for dual therapy.
In all patients, the eradication rates were 80.8% for vonoprazan triple therapy and 77.2% for vonoprazan dual therapy, compared with 68.5% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior, with a difference of 12.3 percentage points for triple therapy and 8.7 percentage points for dual therapy.
Treatment-emergent adverse events were reported in 34.1% of patients in the vonoprazan triple therapy group and 29.9% of patients in the vonoprazan dual therapy group, compared with 34.5% in the lansoprazole triple-therapy group. Most adverse events were mild to moderate.
Serious adverse events occurred in 1.3% of the overall study population, including 1.7% of the vonoprazan triple therapy group, 1.4% of the vonoprazan dual therapy group, and 0.9% of the lansoprazole triple therapy group. None were considered related to the study drugs.
Vonoprazan was approved for the treatment of H. pylori infections by the FDA in May 2022, and had already been approved for treatment of H. pylori infections and other acid-related diseases in several other countries. It decreases intragastric pH and maintains it to a greater degree than that of proton pump inhibitors, which has been associated with higher eradication rates, the authors wrote.
“Optimizing current regimens offers the potential to increase eradication rates and reduce additional antibiotic usage, thereby promoting and improving antimicrobial stewardship,” the study authors wrote.
The study was funded by Phathom Pharmaceuticals, which contributed to the design and conduct of the trial, collection and interpretation of the data, preparation and review of the manuscript, and the decision to submit the manuscript for publication. The study authors declared various conflicts of interest, including some who have received compensation as a consultant, advisory committee member, or employee for Phathom Pharmaceuticals.
Gastric acid inhibition plays a fundamental role for H. pylori eradication. Proton pump inhibitors (PPIs) are generally used, combined with antibiotics, in this scenario. More recently, vonoprazan, a potassium-competitive acid blocker, has been suggested to enhance H. pylori therapy by optimizing gastric acid suppression. However, clinical experience with vonoprazan has been limited to East Asian countries. The study by Chey et al. reports data from the first clinical trial from the United States and Europe, concluding that vonoprazan triple (together with amoxicillin and clarithromycin) and dual (together with amoxicillin) therapies were superior to PPI-based triple therapy, especially in clarithromycin-resistant strains.
However, some aspects deserve to be taken into consideration. The first one is that the cure rate with the standard triple therapy (with lansoprazole) was as low as 68%, underlining what has been known for a long time: This regimen should no longer be considered standard treatment in Europe or the United States and that it should not be recommended in areas with high (>15%) clarithromycin resistance, such as the United States and most European countries.
Secondly, the overall efficacy considering all patients (both with clarithromycin-susceptible and -resistant strains) with vonoprazan dual and triple regimens were of only 77% and 81%, not reaching the recommended target (≥ 90%) for first-line treatment. Therefore, the fair conclusion of the present article should have been not only that vonoprazan regimens are more effective than PPI ones, but also that all of them are insufficiently effective.
Finally, eradication rates in clarithromycin-resistant infections with the vonoprazan regimens (≤ 70%), although superior to those with lansoprazole (32%), were still clearly suboptimal, emphasizing that both PPI and vonoprazan based treatments would be inadequate if used in high-clarithromycin resistance regions.
Javier P. Gisbert, MD, PhD, is with the Hospital Universitario de La Princesa and the Universidad Autónoma de Madrid, both in Madrid. Dr. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.
A look at the data behind the FDA approval
A look at the data behind the FDA approval
Gastric acid inhibition plays a fundamental role for H. pylori eradication. Proton pump inhibitors (PPIs) are generally used, combined with antibiotics, in this scenario. More recently, vonoprazan, a potassium-competitive acid blocker, has been suggested to enhance H. pylori therapy by optimizing gastric acid suppression. However, clinical experience with vonoprazan has been limited to East Asian countries. The study by Chey et al. reports data from the first clinical trial from the United States and Europe, concluding that vonoprazan triple (together with amoxicillin and clarithromycin) and dual (together with amoxicillin) therapies were superior to PPI-based triple therapy, especially in clarithromycin-resistant strains.
However, some aspects deserve to be taken into consideration. The first one is that the cure rate with the standard triple therapy (with lansoprazole) was as low as 68%, underlining what has been known for a long time: This regimen should no longer be considered standard treatment in Europe or the United States and that it should not be recommended in areas with high (>15%) clarithromycin resistance, such as the United States and most European countries.
Secondly, the overall efficacy considering all patients (both with clarithromycin-susceptible and -resistant strains) with vonoprazan dual and triple regimens were of only 77% and 81%, not reaching the recommended target (≥ 90%) for first-line treatment. Therefore, the fair conclusion of the present article should have been not only that vonoprazan regimens are more effective than PPI ones, but also that all of them are insufficiently effective.
Finally, eradication rates in clarithromycin-resistant infections with the vonoprazan regimens (≤ 70%), although superior to those with lansoprazole (32%), were still clearly suboptimal, emphasizing that both PPI and vonoprazan based treatments would be inadequate if used in high-clarithromycin resistance regions.
Javier P. Gisbert, MD, PhD, is with the Hospital Universitario de La Princesa and the Universidad Autónoma de Madrid, both in Madrid. Dr. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.
Gastric acid inhibition plays a fundamental role for H. pylori eradication. Proton pump inhibitors (PPIs) are generally used, combined with antibiotics, in this scenario. More recently, vonoprazan, a potassium-competitive acid blocker, has been suggested to enhance H. pylori therapy by optimizing gastric acid suppression. However, clinical experience with vonoprazan has been limited to East Asian countries. The study by Chey et al. reports data from the first clinical trial from the United States and Europe, concluding that vonoprazan triple (together with amoxicillin and clarithromycin) and dual (together with amoxicillin) therapies were superior to PPI-based triple therapy, especially in clarithromycin-resistant strains.
However, some aspects deserve to be taken into consideration. The first one is that the cure rate with the standard triple therapy (with lansoprazole) was as low as 68%, underlining what has been known for a long time: This regimen should no longer be considered standard treatment in Europe or the United States and that it should not be recommended in areas with high (>15%) clarithromycin resistance, such as the United States and most European countries.
Secondly, the overall efficacy considering all patients (both with clarithromycin-susceptible and -resistant strains) with vonoprazan dual and triple regimens were of only 77% and 81%, not reaching the recommended target (≥ 90%) for first-line treatment. Therefore, the fair conclusion of the present article should have been not only that vonoprazan regimens are more effective than PPI ones, but also that all of them are insufficiently effective.
Finally, eradication rates in clarithromycin-resistant infections with the vonoprazan regimens (≤ 70%), although superior to those with lansoprazole (32%), were still clearly suboptimal, emphasizing that both PPI and vonoprazan based treatments would be inadequate if used in high-clarithromycin resistance regions.
Javier P. Gisbert, MD, PhD, is with the Hospital Universitario de La Princesa and the Universidad Autónoma de Madrid, both in Madrid. Dr. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.
Vonoprazan, a potassium-competitive acid blocker, appears to be superior to standard proton pump inhibitor–based therapy in clarithromycin-resistant Helicobacter pylori strains, as well as noninferior to standard care in nonresistant infections, according to a recent study that supported a Food and Drug Administration approval of vonoprazan dual and triple therapies in May 2022.
For decades, H. pylori has been mostly treated by proton pump inhibitor–based triple therapy, which includes a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. However, eradication rates have dropped below 80% in the United States and Europe, according to the authors, mainly because of rising rates of clarithromycin resistance.
Since H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma, better eradication methods should be highlighted, researchers led by William Chey, MD, professor of medicine and director of the GI Physiology Laboratory at Michigan Medicine in Ann Arbor, wrote in Gastroenterology.
In a multicenter, randomized, controlled, phase 3 trial, the research team studied 1,046 treatment-naive adults with H. pylori infection at 103 sites in the U.S., the U.K., Bulgaria, the Czech Republic, Hungary, and Poland between December 2019 and January 2021.
The patients were randomized to receive open-label vonoprazan dual therapy or a double-blind triple therapy twice a day for 14 days. The vonoprazan dual therapy consisted of 20 mg of vonoprazan twice daily and 1 gram of amoxicillin three times per day. The triple therapy consisted of 20 mg of vonoprazan or 30 mg of lansoprazole (standard care), each given with 1 gram of amoxicillin and 500 mg of clarithromycin.
The primary outcome assessed noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains, with a noninferiority margin of 10%. Secondary outcomes assessed the superiority in eradication rates in clarithromycin-resistant infections, as well as in all patients.
Eradication rates for nonresistant strains were 84.7% for vonoprazan triple therapy and 78.5% for vonoprazan dual therapy, compared with 78.8% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered noninferior to standard therapy.
The eradication rates in clarithromycin-resistant infections were 65.8% for vonoprazan triple therapy and 69.6% in vonoprazan dual therapy, compared with 31.9% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior to standard therapy, with a difference of 33.9 percentage points for triple therapy and 37.7 percentage points for dual therapy.
In all patients, the eradication rates were 80.8% for vonoprazan triple therapy and 77.2% for vonoprazan dual therapy, compared with 68.5% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior, with a difference of 12.3 percentage points for triple therapy and 8.7 percentage points for dual therapy.
Treatment-emergent adverse events were reported in 34.1% of patients in the vonoprazan triple therapy group and 29.9% of patients in the vonoprazan dual therapy group, compared with 34.5% in the lansoprazole triple-therapy group. Most adverse events were mild to moderate.
Serious adverse events occurred in 1.3% of the overall study population, including 1.7% of the vonoprazan triple therapy group, 1.4% of the vonoprazan dual therapy group, and 0.9% of the lansoprazole triple therapy group. None were considered related to the study drugs.
Vonoprazan was approved for the treatment of H. pylori infections by the FDA in May 2022, and had already been approved for treatment of H. pylori infections and other acid-related diseases in several other countries. It decreases intragastric pH and maintains it to a greater degree than that of proton pump inhibitors, which has been associated with higher eradication rates, the authors wrote.
“Optimizing current regimens offers the potential to increase eradication rates and reduce additional antibiotic usage, thereby promoting and improving antimicrobial stewardship,” the study authors wrote.
The study was funded by Phathom Pharmaceuticals, which contributed to the design and conduct of the trial, collection and interpretation of the data, preparation and review of the manuscript, and the decision to submit the manuscript for publication. The study authors declared various conflicts of interest, including some who have received compensation as a consultant, advisory committee member, or employee for Phathom Pharmaceuticals.
Vonoprazan, a potassium-competitive acid blocker, appears to be superior to standard proton pump inhibitor–based therapy in clarithromycin-resistant Helicobacter pylori strains, as well as noninferior to standard care in nonresistant infections, according to a recent study that supported a Food and Drug Administration approval of vonoprazan dual and triple therapies in May 2022.
For decades, H. pylori has been mostly treated by proton pump inhibitor–based triple therapy, which includes a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. However, eradication rates have dropped below 80% in the United States and Europe, according to the authors, mainly because of rising rates of clarithromycin resistance.
Since H. pylori is a leading cause of peptic ulcer, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma, better eradication methods should be highlighted, researchers led by William Chey, MD, professor of medicine and director of the GI Physiology Laboratory at Michigan Medicine in Ann Arbor, wrote in Gastroenterology.
In a multicenter, randomized, controlled, phase 3 trial, the research team studied 1,046 treatment-naive adults with H. pylori infection at 103 sites in the U.S., the U.K., Bulgaria, the Czech Republic, Hungary, and Poland between December 2019 and January 2021.
The patients were randomized to receive open-label vonoprazan dual therapy or a double-blind triple therapy twice a day for 14 days. The vonoprazan dual therapy consisted of 20 mg of vonoprazan twice daily and 1 gram of amoxicillin three times per day. The triple therapy consisted of 20 mg of vonoprazan or 30 mg of lansoprazole (standard care), each given with 1 gram of amoxicillin and 500 mg of clarithromycin.
The primary outcome assessed noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains, with a noninferiority margin of 10%. Secondary outcomes assessed the superiority in eradication rates in clarithromycin-resistant infections, as well as in all patients.
Eradication rates for nonresistant strains were 84.7% for vonoprazan triple therapy and 78.5% for vonoprazan dual therapy, compared with 78.8% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered noninferior to standard therapy.
The eradication rates in clarithromycin-resistant infections were 65.8% for vonoprazan triple therapy and 69.6% in vonoprazan dual therapy, compared with 31.9% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior to standard therapy, with a difference of 33.9 percentage points for triple therapy and 37.7 percentage points for dual therapy.
In all patients, the eradication rates were 80.8% for vonoprazan triple therapy and 77.2% for vonoprazan dual therapy, compared with 68.5% for lansoprazole triple therapy. The rates for both vonoprazan therapies were considered superior, with a difference of 12.3 percentage points for triple therapy and 8.7 percentage points for dual therapy.
Treatment-emergent adverse events were reported in 34.1% of patients in the vonoprazan triple therapy group and 29.9% of patients in the vonoprazan dual therapy group, compared with 34.5% in the lansoprazole triple-therapy group. Most adverse events were mild to moderate.
Serious adverse events occurred in 1.3% of the overall study population, including 1.7% of the vonoprazan triple therapy group, 1.4% of the vonoprazan dual therapy group, and 0.9% of the lansoprazole triple therapy group. None were considered related to the study drugs.
Vonoprazan was approved for the treatment of H. pylori infections by the FDA in May 2022, and had already been approved for treatment of H. pylori infections and other acid-related diseases in several other countries. It decreases intragastric pH and maintains it to a greater degree than that of proton pump inhibitors, which has been associated with higher eradication rates, the authors wrote.
“Optimizing current regimens offers the potential to increase eradication rates and reduce additional antibiotic usage, thereby promoting and improving antimicrobial stewardship,” the study authors wrote.
The study was funded by Phathom Pharmaceuticals, which contributed to the design and conduct of the trial, collection and interpretation of the data, preparation and review of the manuscript, and the decision to submit the manuscript for publication. The study authors declared various conflicts of interest, including some who have received compensation as a consultant, advisory committee member, or employee for Phathom Pharmaceuticals.
FROM GASTROENTEROLOGY
