Experts have touted Vonoprazan as a potentially superior treatment for gastro-oesophageal reflux disease compared to proton pump inhibitors (PPIs). Vonoprazan is an acid-suppressing drug.

Some even claim it is ‘stronger, faster and exhibits longer-lasting acid suppression than conventional PPIs’ for reflux disease including erosive oesophagitis and non-erosive reflux disorder (NERD).

NERD is a common cause of reflux-related symptoms and some patients with NERD fail to respond adequately to PPI therapy.

We take a look at what vonoprazan is and how it works.

What is vonoprazan?

Vonoprazan belongs to a class of drugs known as potassium-competitive acid blockers (PCABs). It inhibits gastric acid secretion by acting as a reversible competitive inhibitor against potassium ions.

More specifically, PCABs block gastric H+, K+-ATPase by K+-competitive ionic binding.

How does this compare with PPIs?

Proton pump inhibitors (PPIs) irreversibly bind to and inhibit the hydrogen-potassium ATPase pump.
In contrast, PCABs interact with the potassium channel adjacent to the proton pump. They bind ionically, unlike PPIs, which bind covalently. This means that the binding action of PCABs is potentially reversible.

Researchers say PCABs’ activity is independent of food intake, and they tend not to interact with other drugs – unlike PPIs, which may interact with other drugs that are metabolised by the cytochrome P450 2C19 enzyme.

Who makes Vonoprazan?

Japanese pharmaceutical company Takeda gained approval for the blocker in 2014 and currently sells it under the brand name Takecab. Phathom Pharmaceuticals, a biopharmaceutical company specialising in gastrointestinal disease treatments, secured an exclusive licence in 2019 to develop and market Vonoprazan in the US, Canada, and Europe.

Then in October 2022, German chemical company Evonik entered into a long-term supply agreement with Phathom Pharmaceuticals to produce large-scale volumes of Vonoprazan at its FDA-inspected manufacturing sites in the US and Germany.

How effective is vonoprazan?

A 2018 study described Vonoprazan as ‘one of the most promising treatment options for patients with PPI-resistant GERD’. The study discovered that switching therapy from a PPI to Vonoprazan improved gastro-oesophageal reflux symptoms in patients with non-erosive reflux disorder (NERD) and PPI-resistant NERD.

While a 2020 study evaluating the efficacy and safety of Vonoprazan for patients with reflux oesophagitis (RE), NERD, and PPI-resistant GERD concluded that its therapy is effective for initial and maintenance therapy in all three groups. In particular, it improved heartburn and patient’s satisfaction. Interestingly, among patients whose symptoms disappeared and stopped taking the medication, 42 per cent of RE and NERD group and 30 per cent of PPI resistant group had no relapse of symptom at 24 weeks.

During the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in October 2022, Phathom presented detailed results from a trial studying Vonoprazan as a daily dosing and on-demand therapy for relief of episodic heartburn in patients with NERD.

Researchers described the results as ‘encouraging’ and demonstrated the potential for patients with non-erosive reflux disorder (NERD) to take Vonoprazan as-needed for rapid and sustained relief from episodic heartburn symptoms.

Are there any concerns about Vonoprazan?

The long-term safety of acid blockers has become a concern for general practitioners as well as gastroenterologists.

Some studies have associated gastric mucosal redness – linear or spotty red areas along the greater curvature of the gastric body – with usage of Vonoprazan. In a 2022 study, both PPI and VPZ use were identified as significant factors contributing to the development of gastric mucosal redness. However, the overall prevalence is low.

Changes in the gut microbiome and bacterial overgrowth have also been reported while increased intestine infection is expected due to the pronounced inhibition of acid secretion.

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