Matthew Hoscheit, MD: Expanding the GERD Treatment Armamentarium with Vonoprazan

Matthew Hoscheit, MD

Credit: Cleveland Clinic

Since the approval of the first proton pump inhibitor (PPI), omeprazole (Prilosec), in 1989, PPIs have been a mainstay of treatment for gastroesophageal reflux disease (GERD), with few innovations seen in the more than 30 years since PPIs first became available.¹

Vonoprazan (Voquezna)’s US Food and Drug Administration (FDA) approval for the healing and maintenance of healing of all grades of erosive GERD as well as the relief of heartburn associated with erosive GERD in 2023 marked the first major transformation in the GERD treatment landscape since omeprazole. Now, less than a year after its approval for erosive GERD, vonoprazan has also earned FDA approval for non-erosive GERD.²

A novel, first-in-class small molecule potassium-competitive acid blocker (PCAB), vonoprazan’s FDA approvals across both erosive and non-erosive GERD add another treatment option to previously available medications and lifestyle interventions to give patients and providers more options for improving or resolving symptoms.²

For further insight into the burden of GERD and the significance of vonoprozan’s most recent approval in non-erosive GERD, the editorial team of HCPLive Gastroenterology spoke with Matthew Hoscheit, MD, a gastroenterologist at Cleveland Clinic.

HCPLive Gastroenterology: Can you describe the burden of non-erosive GERD and what symptoms patients typically present with?

Hoscheit: Distinguishing between erosive and non-erosive GERD is important when discussing the presentation and treatment of GERD. Erosive GERD refers to the formation of ulcers or strictures which can be seen during an upper endoscopy, which signals that damage has been done to the esophagus by acid reflux. Non-erosive GERD, on the other hand, refers to someone having true acid reflux, however, no signs of damage are seen during an upper endoscopy. Erosive and non-erosive disease do not necessarily reflect different severity of symptoms, just different ways GERD can present in people.

The burden of GERD is significant. In 2019, it was estimated that 800 million people worldwide were affected by GERD. This is an increase of almost 80% over the past 20 years, where it was around 440 million people worldwide. Non-erosive GERD makes up the majority of people who are affected by acid reflux. We estimate that approximately 30% of the US population is affected by non-erosive GERD, which makes it even more common than other common diseases, such as diabetes.

The “classic” symptoms of non-erosive or erosive GERD are exactly what people tend to think of when they think about acid reflux. The 2 classic symptoms include heartburn, that burning sensation in your chest, and regurgitation, which refers to fluid coming back up into the esophagus. There are less common symptoms of GERD that are still just as important to look out for. These include chest discomfort, indigestion, sore throat, asthma, chronic cough, and many others.

HCPLive Gastroenterology: What does treatment currently look like for these patients? What are some of the shortcomings of currently available therapies that justify this pipeline development with vonoprazan?

Hoscheit: Fortunately, a variety of medications and lifestyle changes have been shown to be effective for treating and preventing GERD. One of the most effective methods of doing this is with a group of medications called proton pump inhibitors (PPIs). These can be prescribed by a healthcare provider. Medications such as famotidine and calcium carbonate have been shown to be safe and effective in treating heartburn symptoms.

Several lifestyle changes have also been shown to be helpful, including sleeping position (elevating the head of the bed at night with pillows or an adjustable bed frame), sleeping on one's left side, and allowing 3-4 hours between dinner and bedtime. Limiting portion size with meals and avoiding problematic foods can be helpful as well. In certain individuals, weight loss has been shown to help improve heartburn symptoms. It’s best for patients to discuss symptoms with their healthcare providers so that the appropriate treatment can be prescribed.

Vonoprazan is a novel medication that seeks to improve GERD-type symptoms through a different mechanism of action than other medications currently used for acid reflux. While the current over-the-counter and prescription medications we typically use for treating GERD are very effective, no treatment is ever perfect. People may have allergies to these medications that prevent their use, or these medications may just not be effective enough to treat one’s reflux.

Vonoprazan has been FDA-approved recently for the treatment of erosive esophagitis, so a healthcare provider may prescribe the medication to treat individuals with GERD who have ulcers or strictures in their esophagus from their acid reflux. In some recent studies, vonoprazan has been shown to be as effective, if not more effective, than the traditional medications for treating erosive esophagitis. For those individuals with non-erosive esophagitis, however, this medication has not yet been approved for use, though research is being conducted to study its use in this population.

Editors’ note: This Q&A took place prior to the US Food and Drug Administration approval of vonoprazan (Voquenza) for the treatment of heartburn in non-erosive GERD on July 18, 2024. Vonoprazan is now approved for individuals with non-erosive GERD.

HCPLive Gastroenterology: If approved, how do you think vonoprazan could reshape treatment for these patients?

Hoscheit: Having a variety of treatment options for any condition is always an advantage for patients and providers, as people will respond differently to certain treatments. While the majority of individuals with GERD or complications of GERD respond very well to traditional medications and lifestyle changes, there is still a small subset of those who do not. Prior to the development of medications such as vonoprazan, anti-reflux surgeries were generally the remaining treatment we had available to recommend. If vonoprazan is approved by the FDA, it would be another treatment option to offer and help people improve, or even resolve their GERD-type symptoms.

HCPLive Gastroenterology: The current decision is for a daily treatment indication, but vonoprazan is also being investigated as an “as needed” treatment for episodic heartburn relief in non-erosive GERD. Pending phase 3 data confirming the safety and efficacy of such a regimen, what would be the potential benefit of having both daily and as needed dosing regimens available to patients?

Hoscheit: One of the limiting factors of using proton pump inhibitors, one of the most common reflux medications, is that they need to be taken on a daily basis, otherwise they don’t work very well. This can be difficult since it’s hard to remember to take a medication each and every day. Moreover, some people don’t have reflux symptoms on a daily basis, so taking a medication every day can be burdensome and seem unnecessary. If approved by the FDA, having vonoprazan available daily or as needed would allow patients to tailor its use to their specific needs. Of course, patients would need to consult with their healthcare providers for the recommended treatment approach.

Hoscheit has no relevant disclosures of interest.

References

1. ^{Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017;11(1):27-37. doi:10.5009/gnl15502}
2. ^{Brooks, A. Vonoprazan (Voquenza) Receives FDA Approval for Heartburn Associated with Non-Erosive GERD. HCPLive. July 18, 2024. Accessed July 18, 2024. https://www.hcplive.com/view/vonoprazan-receives-fda-approval-for-heartburn-associated-with-non-erosive-gerd}