Chamil Codipilly, MD: Vonoprazan and PCABs for GERD

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Strategic Alliance Partnership | <b>Mayo Clinic Gastroenterology and Hepatology</b>

The potassium-competitive acid blocker drug class is coming to US digestive disease management. How does it fare to standard antacids and PPIs for GERD?

Gastroesophageal reflux disease (GERD) is a highly common inflammatory condition that impacts the digestive system of millions of Americans. Frequently diagnosed and managed by both proven over-the-counter and prescription agents, its status as a health threat is minimal, and its pharmaceutical advancements are practically dormant.

Until potentially very soon.

In an interview with HCPLive, Chamil Codipilly, MD, a gastroenterologist with the Mayo Clinic, discussed the history of GERD pharmaceutical management.

“It’s a huge market out there—as you can probably imagine if you go to your local pharmacy, there’s plenty of medications out there trying to treat this disease,” Codipilly said. “However, I would say that in the last 20-30 years there hasn’t been much in terms of advancements. “

Standard care often calls for over-the-counter antacids like calcium carbonate (Tums) to treat the symptoms of GERD, as well as histamine receptor antagonists designed to help reduce stomach acid. However, they’re limited by waning efficacy associated with continued daily use, Codipilly said.

“I would say probably the game-changer for the management of GERD was in the late 1980s, early 1990s, with the introduction of proton pump inhibitors (PPIs),” he said. “These medications specifically target the pumps in the stomach that secrete the acid and are very effective—probably the most effective medication that we have for management of symptomatic GERD.”

These are overall very effective medications—however, they are limited in relation to the varying metabolization observed among patients with GERD, as well as the challenge of optimal timing associated with best outcomes for each available drug class. Codipilly additionally noted some risk of adverse events with available therapies as well, including absorption issues.

Cue the entry of potassium-competitive acid blockers (PCABs) including Phathom Pharmaceuticals’ vonoprazan, that which the US Food and Drug Administration (FDA) is slated to review as a potential drug for erosive GERD by mid-November.

The agent is designed to resolve the limitation of GERD treatment timing, working on both active and inactive stomach pumps—thereby not requiring patients take it immediately before eating.

“They’re also a little bit quicker in terms of acting,” Codipilly said. “And while they’re newer than the PPIs and we don’t have great long-term safety data, they’ve been used in several Asian countries for a few years now and seem to be very safe.”

PCABs are already in use for the treatment of H. Pylori in the US, which contribute to the safety data. Codipilly additionally referenced recent clinical data showing noninferiority to available PPIs with vonoprazan, including secondary analyses showing potential superiority to the older drug class in more severe cases of GERD.

Codipilly anticipates vonoprazan and the PCAB drug class will eventually be further assessed for treating peptic strictures, as well as for the prevention of progression to cancer among patients with Barrett’s esophagus. What’s more, it may be critical to advance understanding of the drug class as it fares specifically in Americans, who generally follow distinctly different diets and lifestyles than Asian patients.

“We need to get some baseline data to understand how well and how effective this medication is,” Codipilly said. “I think the next steps are going to be refining truly whether it’s something that can be taken as an as-needed basis…and I think another question is going to be the dosage.”