Phathom's old Takeda drug bests Prevacid in a PhIII GI trial. Next stop? The FDA

2021-10-18

There’s no time for rest in biopharma — at least not at Phathom Pharmaceuticals. Just over a month after submitting two NDAs for its lead acid-fighter vonoprazan, the biotech is already lining up a third, and collecting an extra $50 million to push things along. Vonoprazan met its primary non-inferiority endpoints in a Phase III study comparing it to standard-of-care Prevacid in a type of gastroesophageal reflux disease (GERD) called erosive esophagitis (EE). It also proved superior to the popular heartburn drug by multiple measures, including healing rate and maintenance of healing. “The results further solidify vonoprazan’s potential to be the first major innovation in the U.S. and European GERD market in more than 30 years,” CEO Terrie Curran said in a statement. Phathom Pharmaceuticals has come a long way since it was spun out of Takeda, with the help of Frazier, two years ago to handle the ex-Japan development of vonoprazan. Vonoprazan, discovered by Takeda, is a P-CAB: a class of drugs that blocks the potassium-binding site of gastric hydrogen potassium ATPase (also known as the proton pump), which is the enzyme largely responsible for acidification of the stomach. It’s already approved in Japan to treat a variety of acid-related conditions, including EE. The Phase III Phalcon-EE trial enrolled just over 1,000 EE patients in the US and Europe, who were treated with a 20 mg dose of vonoprazan in a healing phase and one of two doses (10 mg or 20 mg) in a maintenance phase. In the healing phase, vonoprazan proved non-inferior to Prevacid in terms of patients who achieved complete healing by Week 8, with a healing rate of 93% in the vonoprazan arm compared to 85% in the Prevacid arm (p<0.0001). It also passed an exploratory superiority test, with a p-value of 0.0001. Patients on vonoprazan saw significantly faster healing in this phase. However, a superiority test comparing a 20 mg dose of vonoprazan to a 30 mg dose of Prevacid for sustained resolution of heartburn by Day 3 did not turn up statistically significant (p=0.2196). Vonoprazan met the primary and all secondary endpoints in the maintenance phase, though, demonstrating superiority in maintenance of healing (79% for vonoprazan 10 mg, 81% for vonoprazan 20 mg, and 72% for Prevacid). The p-values there were less than 0.0001 for both non-inferiority comparisons, 0.0218 for the 10 mg superiority test and 0.0068 for the 20 mg superiority test. Both vonoprazan doses also achieved superiority in the percentage of patients with moderate-to-severe disease who maintained healing of EE through Week 24 (75% for vonoprazan 10 mg, 77% for vonoprazan 20 mg, and 61% for Prevacid). The frequency of serious adverse events were roughly the same in the 20 mg vonoprazan and Prevacid arms of the healing phase, but about twice as high in the 20 mg vonoprazan arm of the maintenance phase, according to Phathom. However, that does include five patients in the 20 mg arm who got Covid-19, which was unrelated to the treatment. The new data will allow Phathom to submit an NDA in the first half of next year, and triggers an extra $50 million from its term loan facility with Hercules Capital. It’s also good news for Catalent, which inked a deal to manufacture the drug just a few weeks ago.

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