First-in-class acid blocker launched for H. pylori, erosive oesophagitis treatment
Vocinti® (vonoprazan), a first-in-class potassium-competitive acid blocker (P-CAB) is now available in Malaysia for use in Helicobacter pylori eradication therapy and erosive (reflux) oesophagitis treatment.
P-CABs suppress stomach acid production by binding proton and ion pumps in gastric parietal cells. While sharing similar chemical properties with proton pump inhibitor (PPI) lansoprazole, vonoprazan appears to remain stable and present in gastric glands for longer periods. A randomized open-label study in healthy adult males found that single-dose vonoprazan helped raise intragastric pH <4 more rapidly and for a greater sustained number of hours versus lansoprazole. [Biochem Pharmacol 2011;81(9):1145–1151; Aliment Pharmacol Ther 2015;42(6):719–730]
“Acid is a key component in both the pathogenesis and treatment of acid-related diseases such as GERD, peptic ulcer disease, H. pylori infection with or without ulcers, dyspeptic conditions, and even gastric cancer,” said Emeritus Professor Dato’ Dr Goh Khean Lee, former president of the Asia Pacific Digestive Week Federation.
Speaking at the recent launch of vonoprazan in Kuala Lumpur, Goh highlighted the need for a better acid-suppressive drug that would also enhance the action of antibiotics in H. pylori eradication therapy. He noted that the present standard 1-week triple therapy with two antibiotics and a PPI, while widely recommended by many consensus panels, yielded eradication rates of only 70 to 80 percent based on Asian and worldwide studies. [J Dig Dis 2010;11(4):244–248; Gut 2007;56(7):1021–1023]
According to Professor Akihito Nagahara, professor and chairman of the Department of Gastroenterology at Juntendo University, Japan, growing antimicrobial resistance (AMR) is the primary reason for the failure of H. pylori eradication therapy. He noted that H. pylori resistance rates to clarithromycin (6.6 to 34.5 percent) and metronidazole (70 to 85 percent) in Asian countries appeared to exceed those in Latin America and Europe. [Arq Gastroenterol 2016;53(4):215–223]
However, the substitution of PPIs with vonoprazan as the acid suppressor in the conventional 1-week triple therapy for H. pylori showed improved primary eradication rates (vonoprazan, 92.6 percent; lansoprazole, 75.9 percent) in a phase III randomized double-blind study in Japan. Vonoprazan showed a similarly higher efficacy even in the treatment of clarithromycin-resistant strains (82.0 vs 40.0 percent). [Gut 2016;65(9):1439–1446]
“There was a gradual decline in [H. pylori] eradication rates from 2001 to 2010—78.5 to 66.5 percent—using the previous 1-week PPI-amoxicillin-clarithromycin regime in clinical practice in Japan,” said Nagahara. [J Gastroenterol Hepatol 2014;29(Suppl 4):29–32]
In erosive oesophagitis treatment, vonoprazan demonstrated similar overall healing rates as lansoprazole over an 8-week period, but more rapid and effective healing for severe (grade C/D) cases in a randomized clinical trial of 409 patients. A subsequent 52-week maintenance study of patients from the same trial found that <10 percent experienced a recurrence of symptoms over a 52-week maintenance period, said Nagahara. [Aliment Pharmacol Ther 2016;43(2):240–251]
“Historically, GERD was thought to be an uncommon disease in Asia, but more recent studies with better defined study methodology have shown otherwise,” said Goh. “We are looking at prevalence of oesophagitis in many Asian countries of up to 15 percent … There is a need for a better drug as far as we are concerned. [J Gastroenterol Hepatol 2014;29(12):1969–1975]
Goh added that there had been a marked increase in oesophagitis diagnoses in Malaysia over the last few decades, noting that time trend studies conducted by his team on endoscopies between 1989 to 2010 showed a rise from 2 to 10 percent across the period. [Aliment Pharmacol Ther 2009;29(7):774–780; 2016;43(7):831–837]