Phathom Pharmaceuticals, Inc. announced that vonoprazan successfully met its primary endpoints and key secondary superiority endpoints in PHALCON-EE, a pivotal phase 3 trial evaluating vonoprazan versus lansoprazole for the treatment of erosive esophagitis. Based on the positive PHALCON-EE data, Phathom plans to submit an NDA to the U.S. Food and Drug Administration seeking the following indications: healing of all grades of EE and relief of heartburn, and maintenance of healing of all grades of EE and relief of heartburn. PHALCON-EE was a trial with two phases. In the first phase, vonoprazan 20 mg was compared to lansoprazole 30 mg in the healing of EE after up to 8 weeks of treatment (Healing Phase). In the Healing Phase, patients were assessed via endoscopy to determine complete healing following 2 weeks of treatment and, if complete healing was not achieved, a second endoscopy occurred at 8 weeks of treatment. Patients who achieved complete healing were re-randomized into the second phase of the trial, where vonoprazan 10 mg and 20 mg were compared to lansoprazole 15 mg to assess maintenance of healing via endoscopy following 24 weeks of treatment (Maintenance Phase). Heartburn symptom relief was assessed via secondary endpoints in both the Healing and Maintenance Phases of the study based on twice daily e-diary data collection. The primary endpoint of the Healing Phase was non-inferiority of vonoprazan 20 mg compared to lansoprazole 30 mg in the percentage of all patients who have complete healing of EE by Week 8. Vonoprazan met the Healing Phase primary endpoint with a healing rate of 93% compared to 85% for lansoprazole (p<0.0001). In a preplanned exploratory superiority test, the difference between vonoprazan and lansoprazole was also significant (p<0.0001). Vonoprazan met the secondary superiority endpoint of healing in patients with moderate-to-severe disease2 at Week 2, demonstrating significantly faster healing than lansoprazole (70% for vonoprazan 20 mg and 53% for lansoprazole 30 mg) (p=0.0004). Vonoprazan 20 mg was also compared to lansoprazole 30 mg in a superiority test for onset of sustained resolution of heartburn by day 3 but did not achieve statistical significance (p=0.2196). In additional secondary endpoint superiority comparisons, vonoprazan 20 mg healing rates were numerically greater than lansoprazole 30 mg in all patients at Week 2 (p=0.0174)3 and in moderate-to-severe patients2 by Week 8 (p<0.0001)3 although deemed nominally significant due to the sequential testing method. Vonoprazan met the primary and all secondary endpoints in the Maintenance Phase. The primary endpoint of the Maintenance Phase was non-inferiority of vonoprazan 10 mg and 20 mg compared to lansoprazole 15 mg in the percentage of all patients who maintained healing of EE through Week 24. Both vonoprazan doses met the Maintenance Phase primary endpoint of non-inferiority while also meeting the secondary comparison demonstrating superiority of maintenance of healing versus lansoprazole (79% for vonoprazan 10 mg, 81% for vonoprazan 20 mg compared to 72% for lansoprazole 15 mg) (p<0.0001 for both non-inferiority comparisons; p=0.0218 for vonoprazan 10 mg superiority comparison; p=0.0068 for vonoprazan 20 mg superiority comparison). Both vonoprazan doses also met the secondary endpoint of demonstrating superiority of the percentage of patients with moderate-to-severe disease4 who maintained healing of EE through Week 24 (75% vonoprazan 10 mg, 77% vonoprazan 20 mg v. 61% lansoprazole 15 mg) (p=0.0245 for vonoprazan 10 mg superiority comparison; p=0.0098 for vonoprazan 20 mg superiority comparison). Additionally, both vonoprazan doses also met the secondary endpoint of showing non-inferiority to lansoprazole 15 mg in the mean percentage of 24-hour heartburn free days over the maintenance period.