In an oral plenary session during ACG, detailed results from the Phase 2 PHALCON-NERD trial studying vonoprazan as a daily dosing and on-demand therapy for relief of episodic heartburn in patients with NERD will be presented by Ronnie Fass, M.D., director of the Division of Gastroenterology and Hepatology and medical director of the Digestive Health Center at MetroHealth in Cleveland, Ohio and lead investigator of the PHALCON-NERD trial. This presentation is the first release of secondary and exploratory endpoint analyses since Phathom shared topline data from the study in February 2022. The double-blind, placebo-controlled PHALCON-NERD study randomized 207 patients who were eligible for on-demand (“as needed”) treatment following a 4-week daily dosing run-in period in which patients received vonoprazan 20 mg once-daily. Patients without heartburn in the last seven days of the run-in period were evenly randomized to receive 10 mg, 20 mg or 40 mg of vonoprazan or placebo for six weeks. The primary endpoint was met for all three doses of vonoprazan, demonstrating complete and sustained relief in 56% (10 mg), 60.6% (20 mg) and 70% (40 mg) of heartburn episodes was achieved within three hours with no further heartburn reported for 24 hours in the on-demand period, compared to placebo (27.3%, p In exploratory endpoints, the onset of complete and sustained relief of heartburn episodes was also evaluated at intervals of 30 minutes, 1 hour, 1.5 hours, 2 hours, and 3 hours after taking vonoprazan to determine the earliest point of complete symptom relief. Significant differences in complete and sustained relief occurred across all doses of vonoprazan in as early as one hour after dosing in the on-demand period and was maintained for over 24 hours. In the on-demand period, vonoprazan had no treatment-emergent adverse events (AEs) reported by >1 patient per treatment group. Additionally, 16.3%, 18.4%, and 16.7% of patients treated with vonoprazan 10, 20, and 40 mg, respectively reported a treatment-emergent adverse event (TEAE) compared to 21.3% of patients receiving placebo. “These results from the Phase 2 PHALCON-NERD study are very encouraging and demonstrate the potential of vonoprazan to be taken as-needed by patients with NERD who experience episodic heartburn symptoms and require rapid and sustained relief,” said Ronnie Fass, M.D. “NERD is a common cause of reflux-related symptoms and some patients with NERD fail to respond adequately to PPI therapy. This study suggests that the rapid suppression of gastric acid by vonoprazan translates into clinical benefits for patients with NERD when taken on demand.” In addition, Phathom is actively conducting a Phase 3 PHALCON-NERD Daily Dosing trial to evaluate vonoprazan as a daily dosing treatment of heartburn associated with NERD. Topline data for the primary endpoint are expected in early 2023, with full results expected in late 2023. “The data being presented at this year’s ACG further highlights Phathom’s commitment to its mission to transform treatment for patients with gastrointestinal diseases and disorders,” said Azmi Nabulsi, M.D., Chief Operating Officer at Phathom. “We are excited to share more detailed results of our Phase 2 on-demand trial and look forward to generating additional insights about vonoprazan as a potential daily preventative therapy in patients with NERD in our ongoing Phase 3 trial. Our continued research program demonstrates the promise of a new mechanism of action to provide more effective acid control with the potential to address unmet needs in the treatment of NERD and other acid-related GI conditions.” Also during ACG, Dr. Carmelo Scarpignato, Professor of Medicine & Clinical Pharmacology at the United Campus of Malta, and General Secretary, World Organization for Esophageal Diseases (OESO), will present a poster (Presentation #: E0193) on a pharmacokinetics (PK) and pharmacodynamics (PD) study. Pooled data from five Phase 1 studies were used to develop a PK/PD model to investigate the relationship between vonoprazan treatment and pH HTR. The pooled data included pH measurements for 245 participants from Japan and Western countries. Simulations showed that vonoprazan 20 mg once-daily (QD) and 20 mg twice-daily (BID) are predicted to give pH>4 HTRs of 89.7% and 98.1%, respectively, by Day 7. HTRs for pH>6 were 53.1% for vonoprazan 20 mg QD and 75.3% for BID. Following the conclusion of ACG 2022, the abstracts will be posted to Phathom’s publications and scientific section of the company website. NERD is the largest subcategory of gastroesophageal reflux disease (GERD) and is characterized by reflux-related symptoms in the absence of esophageal mucosal erosions.1,2 There are estimated to be over 65 million individuals with GERD in the U.S., and it is estimated that seventy percent (70%) of this population have NERD. Symptoms of NERD impact overall quality of life and can include episodic heartburn, especially at night, regurgitation, problems swallowing, and chest pain.3,4 To reduce the development of drug-resistant bacteria and maintain the effectiveness of VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK, and other antibacterial drugs, both products should be used only to treat or prevent infections that are proven or strongly suspected of being caused by bacteria. VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK are contraindicated in patients with known hypersensitivity to vonoprazan or amoxicillin, any other components of the formulation, any other beta-lactams, or in patients receiving rilpivirine-containing products. Hypersensitivity Reactions: Serious and occasionally fatal reactions (e.g., anaphylaxis) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If hypersensitivity reactions occur, discontinue use and institute immediate therapy (e.g., anaphylaxis management). Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Assess CgA levels at least 14 days after VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK treatment and consider repeating the test if initial CgA levels are high. VOQUEZNA TRIPLE PAK Warnings or Precautions Due to the Clarithromycin Component: Hepatotoxicity: Discontinue use of VOQUEZNA TRIPLE PAK if signs and symptoms of hepatitis occur. Embryo-Fetal Toxicity: VOQUEZNA TRIPLE PAK is not recommended for use in pregnancy as clarithromycin may cause fetal harm. Components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK have the potential for clinically important drug interactions. See full Prescribing Information for important drug interactions.
USE IN SPECIFIC POPULATIONS
Lactation: Breastfeeding not recommended during treatment, but a lactating woman can pump and discard breast milk during treatment and for 2 days after VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK administration.
Geriatrics: VOQUEZNA TRIPLE PAK increased risk of torsades de pointes due to clarithromycin. You are encouraged to report suspected adverse reactions by contacting Phathom Pharmaceuticals at 1-888-775-PHAT (7428) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see full Prescribing Information for VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK.
Phathom cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company’s current beliefs and expectations. The inclusion of forward-looking statements should not be regarded as a representation by Phathom that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Phathom’s business, including, without limitation: the inherent risks of clinical development of vonoprazan; Phathom’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; regulatory developments in the United States and foreign countries; Phathom’s ability to successfully launch and commercialize vonoprazan; unexpected adverse side effects or inadequate efficacy of vonoprazan that may limit its development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; Phathom’s ability to obtain and maintain intellectual property protection for vonoprazan; Phathom’s ability to comply with its license agreement with Takeda; Phathom’s ability to maintain undisrupted business operations due to the ongoing impact of the COVID-19 coronavirus, including delaying or otherwise disrupting its clinical trials, manufacturing and supply chain and launch and commercialization efforts; Phathom’s ability to achieve and maintain adequate levels of coverage and reimbursement for vonoprazan; Phathom’s ability to access additional capital under its term loan facility is subject to certain conditions, and other risks described in the Company’s prior press releases and the Company’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Phathom undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. INVESTOR AND MEDIA CONTACT
___________________________
1 Chen CL, Hsu PI. Current advances in the diagnosis and treatment of nonerosive reflux disease. Gastroenterol Res Pract. 2013;2013:653989. 4 Modlin IM, Hunt RH, Malfertheiner P, Moayyedi P, Quigley EM, Tytgat GN, et al; Vevey NERD Consensus Group. Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group. Digestion. 2009;80(2):74-88.