Positive topline data were announced from a phase 3 trial evaluating vonoprazan for eradication of Helicobacter pylori (H. pylori) infection.
Vonoprazan is an oral small molecule potassium-competitive acid blocker that has been shown to have rapid and durable anti-secretory effects. The PHALCON-HP trial (N=992) (ClinicalTrials.gov: NCT04167670) compared 2 vonoprazan-based regimens (dual therapy with amoxicillin and triple therapy with amoxicillin and clarithromycin) with lansoprazole in combination with amoxicillin and clarithromycin. Each treatment regimen was administered for 14 days.
Results showed that in the modified intent-to-treat (mITT) population, H. pylori eradication rates were 78.5% and 84.7% with vonoprazan dual and triple therapy, respectively, compared with 78.8% with lansoprazole triple therapy (P <.0001 and P =.0037 for non-inferiority [primary endpoint]). In the per protocol population (n=822), H. pylori eradication rates were 81.2% and 90.4% with vonoprazan dual and triple therapy, respectively, compared with 82.1% with lansoprazole triple therapy (P <.0001 and P =.0077 for non-inferiority).
In the subset of patients with H. pylori strains resistant to clarithromycin, both vonoprazan-based regimens were found to be superior to lansoprazole triple therapy.
- Vonoprazan dual therapy vs lansoprazole triple therapy:
- mITT: 69.6% vs 31.9%; P <.0001
- per protocol: 79.5% vs 29.0%; P <.0001
- Vonoprazan triple therapy vs lansoprazole triple therapy:
- mITT: 65.8% vs 31.9%; P <.0001
- per protocol: 67.2% vs 29.0%; P <.0001.
As for safety, the most commonly reported adverse events in the vonoprazan dual and triple therapy arms compared with the lansoprazole triple therapy arm included diarrhea (5.2%, 4.0% vs 9.6%), dysgeusia (0.6%, 4.3%, vs 6.1%), nausea (1.7%, 1.7% vs 2.6%), headache (1.4%, 2.6% vs 1.4%) and vaginal infections (0.9%, 2.3% vs 0.3%). Rates of discontinuation were 0.9% for vonoprazan dual therapy, 2.3% for vonoprazan triple therapy, and 1.4% for lansoprazole triple therapy.
“We believe the topline results of our PHALCON-HP study support the potential of vonoprazan-based therapies to change H. pylori treatment,” said Terrie Curran, Phathom’s President and Chief Executive Officer. “We plan to submit NDAs with the FDA for vonoprazan dual and triple therapy in H. pylori before the end of the year.”
Phathom Pharmaceuticals announces positive topline results from pivotal phase 3 trial of vonoprazan in Helicobacter pylori (H. pylori) infection; study met all primary and secondary endpoints. [press release]. Florham Park, NJ: Phathom Pharmaceuticals; April 29, 2021.