FDA approves two vonoprazan treatment regimens for H. pylori infection
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Phathom Pharmaceuticals Inc. has announced FDA approval for its Voquezna Triple and Dual Paks for the treatment of Helicobacter pylori infection in adults.
According to a press release, the new drug applications for Voquenza Triple Pak (vonoprazan tablets, amoxicillin capsules, clarithromycin tablets; Phathom Pharmaceuticals) and Voquenza Dual Pak (vonoprazan tablets, amoxicillin capsules; Phathom Pharmaceuticals) were given priority review designation by the FDA after previous classification as qualified infectious disease products. Both regimens contain vonoprazan, an innovative potassium-competitive acid blocker, and are supplied in blister packs to promote compliance.
“These new regimens usher in the next generation of H. pylori treatment,” William D. Chey, MD, AGAF, FACG, FACP, professor of medicine and chief of gastroenterology and hepatology at the University of Michigan, told Healio. “Vonoprazan provides more profound and durable gastric acid suppression than traditional [proton pump inhibitors (PPIs)] that, when used empirically, translate into higher eradication rates than PPI-based triple therapy.”
In the pivotal phase 3 PHALCON-HP trial, which randomized 1,046 patients with H. pylori to one of the vonoprazan treatment regimens or lansoprazole triple therapy, the two regimens demonstrated noninferiority compared with lansoprazole triple therapy in patients without a clarithromycin or amoxicillin resistant H. pylori strain. Vonoprazan also showed superior eradication rates vs. PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in all patients, including those with clarithromycin-resistant strains of H. pylori.
In the overall study population, the H. pylori eradication rate was 80.8% with the Voquenza Triple Pak vs. 68.5% with lansoprazole triple therapy; similarly, the eradication rate was 77.2% with the Voquenza Dual Pak vs. 68.5% with lansoprazole triple therapy.
Phathom Pharmaceuticals expects to launch the vonoprazan treatment regimens in the United States in the third quarter of 2022.
Perspective
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Adrienna Jirik, MD
The development of new non-PPI therapy regimens to treat H. pylori is a welcome addition to the current arsenal of therapeutics, especially given the concerning rise in refractory infections. What is immediately noticeable with the new regimens is that they are very familiar — a variation on the amoxicillin/clarithromycin recipe, dressed up with an alternative potent acid suppressor, vonoprazan.
Along with microbial resistance, host genetics have also been implicated in H pylori treatment failures for PPI-based therapies due to variations in intragastric pH, the control of which is key for H. pylori eradication. Metabolism enhancing phenotypes of CYP2C19 (a cytochrome P450 pathway responsible for the most commonly used PPIs), which are noted to be prevalent in Hispanic, Black and white populations, have been associated with treatment failures using PPIs.
Vonoprazan is a potassium-competitive acid inhibitor (PCAB) which reversibly inhibits the secretion of gastric acid by competing for potassium on the H+/K+ATpase pump of parietal cells in the gastric lumen. Unlike PPIs, which takes at least 72 hours for optimal acid suppression, PCABs work immediately to increase gastric pH, with bioavailability not affected by oral intake. This makes vonoprazan an especially powerful tool: It not only markedly enhances the half-lives of the antibiotics (amoxicillin in particular), but it also increases and maintains the ideal pH for H. pylori replication (between 6-8), which makes them much more susceptible to antibiotics.
The study results are very encouraging, and it will be interesting to evaluate efficacy of PCABs with other available antibiotic regimens for H. pylori.
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