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
FLORHAM PARK, NJ, USA I April 29, 2021 I Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a late clinical-stage biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal diseases, announced today that in PHALCON-HP, its pivotal Phase 3 clinical trial for the eradication of H. pylori infection, both vonoprazan-based regimens successfully met their primary endpoints and met all secondary endpoints. The trial studied vonoprazan in combination with amoxicillin and clarithromycin (“vonoprazan triple therapy”) and vonoprazan in combination with amoxicillin (“vonoprazan dual therapy”) compared to lansoprazole in combination with amoxicillin and clarithromycin (“lansoprazole triple therapy”). PHALCON-HP is the largest Phase 3 registration trial ever conducted in H. pylori infection, randomizing 992 patients with confirmed H. pylori infection.
Phase 3 Topline Results
Primary endpoint analysis
The primary endpoints in the PHALCON-HP study were non-inferiority of the H. pylori eradication rate for each of vonoprazan triple and dual therapy compared to lansoprazole triple therapy. Based on U.S. Food and Drug Administration (FDA) feedback, the primary endpoint excluded patients with amoxicillin or clarithromycin resistant strains of H. pylori.
Both vonoprazan-based regimens successfully met their primary endpoints. In the modified intent-to-treat (mITT) population, H. pylori eradication rates were 84.7% with vonoprazan triple therapy and 78.5% for vonoprazan dual therapy compared to 78.8% with lansoprazole triple therapy (p<0.0001 and p=0.0037, respectively, for non-inferiority).
Additional efficacy analyses were conducted using the pre-specified per protocol population, a subset of the mITT population comprised of patients who were protocol compliant as defined by FDA draft Guidance for Industry1. In the per protocol population, H. pylori eradication rates were 90.4% with vonoprazan triple therapy and 81.2% with vonoprazan dual therapy compared to 82.1% with lansoprazole triple therapy (p<0.0001 and p=0.0077, respectively, for non-inferiority).
Secondary endpoint analysis
Vonoprazan triple therapy and vonoprazan dual therapy also met all secondary endpoints, demonstrating superior eradication rates versus lansoprazole triple therapy in all patients and patients with clarithromycin resistant strains of H. pylori. Patients with clarithromycin resistant strains comprised 20.3% of the PHALCON-HP study population.
Vonoprazan triple therapy
The H. pylori eradication rate of vonoprazan triple therapy was superior to that of lansoprazole triple therapy among all patients in both the mITT population (80.8% vs. 68.5%; p=0.0001) and the per protocol population (85.7% vs. 70.0%; p<0.0001).
The H. pylori eradication rate with vonoprazan triple therapy was superior to that of lansoprazole triple therapy in the subset of patients with H. pylori strains resistant to clarithromycin in both the mITT population (65.8% vs. 31.9%; p<0.0001) and the per protocol population (67.2% vs. 29.0%; p<0.0001).
Vonoprazan dual therapy
The H. pylori eradication rate of vonoprazan dual therapy was superior to that of lansoprazole triple therapy among all patients in both the mITT population (77.2% vs. 68.5%; p=0.0063) and the per protocol population (81.1% vs. 70.0%; p=0.0013).
The H. pylori eradication rate of vonoprazan dual therapy was superior to that of lansoprazole triple therapy in the subset of patients with H. pylori strains resistant to clarithromycin in both the mITT population (69.6% vs. 31.9%; p<0.0001) and the per protocol population (79.5% vs. 29.0%; p<0.0001).
“Acid suppression is a key factor in addressing shortcomings associated with currently available H. pylori treatments, especially in light of increased resistance to antibiotics, including clarithromycin,” said Professor William D. Chey, M.D., AGAF, FACG, FACP, Professor of Medicine and Director of the GI Physiology Laboratory at the University of Michigan. “I am very impressed with the results of PHALCON-HP which demonstrate that replacing a PPI with vonoprazan in H. pylori treatment regimens has the potential to meaningfully enhance eradication rates that have been declining over the last two decades. Further, the potential to limit the use of clarithromycin with a dual therapy regimen has the potential to transform clinical practice.”
Safety profile
Both vonoprazan-based regimens were generally well tolerated with a safety profile comparable to lansoprazole triple therapy. The most common adverse events (>2.0%) reported in the vonoprazan triple therapy, vonoprazan dual therapy, and lansoprazole triple therapy arms, respectively, were diarrhea (4.0%, 5.2%, and 9.6%), dysgeusia (4.3%, 0.6%, and 6.1%), nausea (1.7%, 1.7% and 2.6%), headache (2.6%, 1.4%, 1.4%) and vaginal infections (2.3%, 0.9%, 0.3%). Overall rates of discontinuation due to adverse events were 2.3% for vonoprazan triple therapy-treated patients, 0.9% for vonoprazan dual therapy-treated patients, and 1.4% for lansoprazole triple therapy-treated patients.
Full results from the PHALCON-HP study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.
About Helicobacter pylori (H. pylori) infection
H. pylori is a bacterial pathogen that is estimated to infect over 200 million individuals in the United States and Europe. Approximately 50% of the world and 36% of the US population are infected with the bacterium.2 In many cases, H. pylori is acquired in childhood and through intrafamilial transmission.3 As a result of the chronic inflammation induced by H. pylori infection, infected patients develop a range of pathologies including dyspepsia, peptic ulcer disease, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma.4 Studies have found that roughly 1 in 5 patients treated for H. pylori will fail first line therapy when using standard clarithromycin triple therapy.2,5
About PHALCON-HP
PHALCON-HP was a randomized, multicenter, Phase 3 trial that enrolled 1046 patients of which 992 patients with a confirmed H. pylori infection were randomized to one of three arms: vonoprazan 20 mg administered twice a day (BID) and amoxicillin 1g administered three times a day (TID) (n=324); vonoprazan 20 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID (n=338); and lansoprazole 30 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID (n=330). Each treatment regimen was administered for 14 days. Diagnoses of infection and test of cure were confirmed by 13C-urea breath test. Additional efficacy analyses were conducted using the pre-specified per protocol population (n=822), a subset of the mITT population comprised of patients who were protocol compliant.
About Vonoprazan
Vonoprazan is an investigational, oral small molecule potassium-competitive acid blocker (P-CAB). P-CABs are a novel class of medicines that block acid secretion in the stomach. Vonoprazan has shown the potential to have rapid, potent, and durable anti-secretory effects as a single agent in the treatment of gastroesophageal reflux disease (GERD) and in combination with antibiotics for the treatment of Helicobacter pylori (H. pylori) infection. The FDA has awarded Fast Track designation to vonoprazan in combination with both amoxicillin and clarithromycin and with amoxicillin alone for the treatment of H. pylori infection. Phathom in-licensed the U.S., European, and Canadian rights to vonoprazan from Takeda, which completed 19 Phase 3 trials for vonoprazan and received marketing approval in Japan and numerous other countries in Asia and Latin America.
About Phathom
Phathom Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel treatments for gastrointestinal diseases and disorders. Phathom has in-licensed the exclusive rights in the United States, Europe, and Canada to vonoprazan, a novel potassium competitive acid blocker (P-CAB) in late-stage development for the treatment of acid-related disorders. For more information about Phathom, visit the Company’s website at www.phathompharma.com or follow the Company on social media: LinkedIn at www.linkedin.com/company/phathompharma and Twitter @PhathomPharma.
1https://www.fda.gov/regulatory-information/search-fda-guidance-documents/helicobacter-pylori-associated-duodenal-ulcer-disease-adults-developing-drugs-treatment
2 Hooi et al. Gastroenterology. 2017;153:420.
3 Chey et al. Am J Gastroenterol.2017;112:212.
4 Malfertheiner et al. Gut. 2017;66:6.
5 Alsamman et al. Dig Dis Sci. 2019;64:2893.
SOURCE: Phathom Pharma
Published on Friday, 30 April 2021
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