Fexuprazan brings relief in erosive esophagitis, noninferior to esomeprazole

The novel potassium-competitive acid blocker fexuprazan shows comparable safety and efficacy to the proton pump inhibitor esomeprazole in the treatment of Chinese patients with erosive esophagitis, as shown in the results of a phase III study presented at DDW 2023.

In the per-protocol analysis, the primary endpoint of the cumulative healing rate after 8 weeks of treatment was 97.3 percent with fexuprazan vs 97.9 percent with esomeprazole. The difference of –0.7 percent (95 percent confidence interval [CI], –4.2 to 2.7) established the noninferiority of fexuprazan. [DDW 2023, abstract 1303]

Notably, the proportion of patients with healed erosive esophagitis at week 4 was slightly higher in the fexuprazan group than in the esomeprazole group (84.6 percent vs 80.8 percent).

With regard to heartburn and acid regurgitation, the proportion of patients and the number of days without these symptoms were not significantly different between fexuprazan and esomeprazole groups (p>0.05).

The most common adverse drug reactions were hyperuricaemia and liver dysfunction (3 percent), and the frequency of drug-related treatment-emergent adverse events was similar in the two treatment groups.

The phase III study included 332 adult patients with endoscopically confirmed erosive esophagitis (LA Grades A to D). They were randomly assigned to receive either fexuprazan 40 mg or esomeprazole 40 mg once daily.

Meal timing not necessary for optimal action

“Fexuprazan … is developed for the treatment of acid-related disorders, [and the drug’s] pharmacokinetic and pharmacodynamic properties … are independent of the food effect,” according to Dr In-Kyung Sung of the School of Medicine at Konkuk University, Seoul, Republic of Korea, who presented a separate study at DDW 2023.

Sung and colleagues conducted a double-blind, multicentre study involving 186 patients with endoscopically confirmed erosive esophagitis who were randomly assigned to receive fexuprazan 40 mg once daily, 30 minutes before (n=92) or after a meal (n=92). Of these patients, 157 completed the treatment after 2 or 4 weeks when healing was endoscopically confirmed (80 and 77 patients, respectively).

The primary endpoint of healing rate at week 4 did not differ by dosing timing: 98.77 percent in the before-meal group and 100.00 percent in the after-meal group (difference, 0.01 percent, 95 percent CI, –0.01 percent to 0.04 percent). [DDW 2023, abstract 1311]

The same was true for the 2-week healing rate, being 95.77 percent in the before-meal group and 97.14-percent in the after-meal group (difference, 0.01 percent, 95 percent CI, –0.05 percent to 0.07 percent).

Treatment-emergent adverse events were 9.78 percent and 8.70 percent in the before-meal and after- meal groups, respectively. The corresponding frequencies of adverse drug reactions were 4.35 percent and 5.43 percent.

“Proton pump inhibitors are considered the most effective medical therapy for gastroesophageal reflux disease, but they should be taken no more than 30 minutes prior to the first meal of the day,” Sung said.

The present data confirm that fexuprazan is safe and efficacious for healing erosive esophagitis regardless of the timing of dosing, he added.

“Therefore, fexuprazan 40 mg could be a good alternative to proton pump inhibitors and also improve patient compliance,” Sung concluded.