Vonoprazan Fumarate Tablets (Voquezna)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California San Francisco.

The U.S. Food and Drug Administration (FDA) has approved vonoprazan for the treatment of all grades of erosive esophagitis. Vonoprazan is a potassium-competitive acid blocker that originally was approved in 2022 for use in combination with amoxicillin or with amoxicillin and clarithromycin for the treatment of Helicobactor pylori infection. It is marketed by Phathom Pharmaceuticals Inc. as Voquezna.

INDICATIONS

Vonoprazan is indicated for healing and to maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.¹

DOSAGE

The recommended dose for healing of erosive esophagitis is 20 mg daily for eight weeks.¹ The dose is reduced to 10 mg once daily in those with glomerular filtration rate (GFR) < 30 mL/min. For the maintenance of healed erosive esophagitis, the recommended dose is 10 mg once daily for up to six months. Vonoprazan is available as 10 mg and 20 mg tablets.

POTENTIAL ADVANTAGES

A potassium-competitive acid blocker provides more rapid and potent inhibition of gastric acid than proton pump inhibitors (PPIs) as it binds to active and inactive proton pumps while PPIs only inhibit active proton pumps.² Vonoprazan produced a higher proportion of a 24-hour period with intragastric pH > 4 than lansoprazole on day 1 (62.4% vs. 22.6%) and 87.8% vs. 42.3% on day 7.² Vonoprazan has a long elimination half-life (approximately eight hours) and does not require formulation to protect against gastric acid (i.e., enteric coating, delayed release formulation or as a prodrug). Vonoprazan can be administrated without regard to meals while PPIs should be administered 30 to 60 minutes prior to meals. There are no differences in pharmacokinetics of vonoprazan based on CYP2C19 metabolizer status, a primary metabolic pathway for PPIs.¹

POTENTIAL DISADVANTAGES

Vonoprazan carries similar warnings and precautions as PPIs, including Clostridioides difficle-associated diarrhea, bone fracture and osteoporosis-related fracture, vitamin B12 deficiency, and fundic gland polyps. Vonoprazan causes greater increase in serum gastrin compared to lansoprazole (mean 158 [144] pg/mL vs. 64 [69] pg/mL). Hypergastrinemia may be associated with enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumor, gastric cancer, and Barrett’s related esophageal adenocarcinoma.³

COMMENTS

The efficacy of vonoprazan was evaluated in a randomized, active-controlled, double-blind, eight-week study in adult participants with H. pylori-negative, endoscopically confirmed erosive esophagitis.^1,4 Those with Barrett’s esophagitis and/or dysplastic changes in the esophagus at baseline were excluded. The majority were white (90%) and 54% were female. Two-thirds had mild erosive esophagitis (Los Angeles [LA] Classification A or B) and about one-third had moderate to severe disease (grades C and D). Participants were randomized to vonoprazan 20 mg (n = 514) or lansoprazole 30 mg (n = 510). Participants who achieved healing were re-randomized for 24 weeks for assessing maintenance of healing. The primary endpoint for the healing phase was the percent with healing at week 2 or 8 and the primary endpoint for the maintenance phase was the percentage who maintained healing after 24 weeks. Healing of all LA grades of erosive esophagitis were 93% for vonoprazan vs. 85% for lansoprazole, demonstrating noninferiority to lansoprazole. There was no difference in median 24-hour heartburn-free days (81% vs. 78%). In a subgroup analysis, healing for LA grade A/B was comparable at week 8 (93.5% vs. 91.2%). However, healing at week 2 superiority was demonstrated in those with LA grade C or D disease (70% vs. 53%). In the maintenance phase, participants were randomized to vonoprazan 20 mg, 10 mg, or lansoprazole 15 mg. Percentage healing maintained were 80.7%, 79.2%, and 72%, respectively. Percentage healing maintained for LA grade C/D was 77.2%, 74.7%, and 61.5%, respectively, showing both doses superior to lansoprazole but no additional benefit with the higher dose of vonoprazan. The median of 24-hour heartburn-free days through week 24 was 95% vs. 89%.

CLINICAL IMPLICATIONS

Gastroesophageal reflux disease is a common gastrointestinal disorder with a prevalence of 21%.⁴ About one-fourth to one-half of cases develop erosive esophagitis. PPIs are the mainstay of therapy for erosive esophagitis;⁵ however, up to 40% of patients do not respond adequately to PPI therapy.⁶ The findings from this comparative trial are limited to lansoprazole and may not be completely generalizable to the PPIs as a class as relative potencies of standard-dose differ. With omeprazole as the reference (potency = 1), lansoprazole has a potency of 0.90 while esomeprazole has a comparative potency of 1.60, and rabeprazole is at 1.82.⁷ The percentage of time vonoprazan 10 mg maintains gastric pH above 4 over a 24-hours period (approximatley 60%) is equivalent to omeprazole 60 mg once daily and vonoprazan 20 mg is equivalent to omeprazole 60 mg twice daily.Studies to date with vonoprazan mainly have been in Asian participants. More studies in Western subjects as well as with more potent PPIs would determine if vonoprazan can be a viable option in in patients with severe erosive esophagitis (i.e., LA Class C/D), PPI-refractory patients, as well as extensive CYP2C19 metabolizers. Cost will also be a factor, as vonoprazan costs $650 for 30 tablets while PPIs are available as generic as well as over-the-counter for as little as $10 for 30 pills.

REFERENCES

1. Voquezna Prescribing Information. Phathom Pharmaceuticals Inc. November 2023. https://voqueznapro.com/erosive-gerd?gclid=Cj0KCQiAsburBhCIARIsAExmsu7LyAsN-BzLZ4ZA0iizDjcD5m8AIGQMXZisCTOOHWviU5I49I19YskaAtsvEALw_wcB&gclsrc=aw.ds
2. Laine L, Sharma P, Mulford DJ, et al. Pharmacodynamics and pharmacokinetics of the potassium-competitive acid blocker vonoprazan and the proton pump inhibitor lansoprazole in US subjects. Am J Gastroenterol 2022;117:1158-1161.
3. Lundell L, Vieth M, Gibson F, et al. Systematic review: The effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology. Aliment Pharmacol Ther 2015;42:649-663.
4. Laine L, DeVault K, Katz P, et al. Vonoprazan versus lansoprazole for healing and maintenance of healing of erosive esophagitis: A randomized trial. Gastroenterol 2023;164:61-71.
5. Katz PO, Dunbar KB, Schnoll-Sussman F, et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022;117:27-56.
6. Rettura F, Bronzini F, Campigotto M, et al. Refractory gastroesophageal reflux disease: A management update. Front Med (Lausanne) 2021; Nov 1:8:765061. doi: 10.3389/fmed.2021.765061.
7. Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 2018;16:800-808.e7.