Vonoprazan Fumarate

FLORHAM PARK, N.J., Oct. 27, 2024 (GLOBE NEWSWIRE) -- Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal (GI) diseases, today announced that the company will present data from multiple investigational studies for its first-in-class treatment VOQUEZNA® (vonoprazan) tablets at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting, being held October 25-30 in Philadelphia, PA. VOQUEZNA is approved for the relief of heartburn associated with Non-Erosive Gastroesophageal Reflux Disease (Non-Erosive GERD), for the treatment of all severities of Erosive Esophagitis, commonly referred to as Erosive GERD, and relief of related heartburn, and in combination with antibiotics for the eradication of Helicobacter pylori (H. pylori) infection.1 VOQUEZNA is the first and only U.S. Food and Drug Administration (FDA)-approved potassium-competitive acid blocker (PCAB).2 Evaluating On-Demand VOQUEZNA Treatment from the PHALCON-NERD-201 Trial3In an oral presentation being presented Monday, October 28 at ACG, 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-201 trial, will provide results from a post-hoc analysis of the Phase 2 study. This research, recognized with the ACG Outstanding Research Award in the ‘Esophagus’ category, evaluated the efficacy of As Needed (On-Demand) dosing of VOQUEZNA, compared to placebo, for relief of episodic heartburn in participants with Non-Erosive GERD following a 4-week VOQUEZNA daily dosing “run-in” period. As previously reported, the primary analysis of the study demonstrated that all three VOQUEZNA doses tested (10 mg, 20 mg and 40 mg) had higher percentages of heartburn completely relieved within three hours of dosing and sustained for 24 hours, with significant differences reported as early as one hour. Use of As Needed dosing in this population is investigational as VOQUEZNA has been neither evaluated nor approved by the FDA as an As Needed treatment for Non-Erosive GERD. To understand the practical application of As Needed dosing for VOQUEZNA, the new analysis examined daily heartburn symptom burden at baseline, during daily VOQUEZNA treatment, and upon switching to As Needed treatment after achieving symptom control during the run-in period. It also further evaluated the rate of symptom improvement upon treating new onset heartburn episodes during the As Needed dosing period.3 “As a healthcare provider, the concept of a novel As Needed dosing option for Non-Erosive GERD is highly compelling. I am pleased that ACG has recognized this data as a recipient of the ACG Outstanding Research Award, further reinforcing its importance to the GI community,” said Ronnie Fass, M.D. “The low frequency of heartburn after discontinuing daily VOQUEZNA treatment, coupled with the rapid onset of improvement following As Needed dosing, suggests that transitioning from daily dosing to As Needed treatment is a viable option for patients who previously respond well to daily therapy of VOQUEZNA. These promising results warrant further investigation in a larger and extended As Needed study period.” The double-blind, placebo-controlled PHALCON-NERD Phase 2 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 VOQUEZNA 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 VOQUEZNA, or placebo, for six weeks. Results of the study were published in Alimentary Pharmacology & Therapeutics in September 2023.4 Results:3 Patients eligible for the On-Demand period (n=207) were highly symptomatic with a reported mean of 16.1% [95% CI: (13.5%, 18.7%)] heartburn-free days during screening. Heartburn-free days increased during the run-in period to a mean of 82.9% [95% CI: (80.4%, 85.4%)] and remained well above pre-treatment levels (means 71% to 75%) throughout the six-week On-Demand period.The difference in the improvement of treated heartburn episodes between the active and placebo groups became evident within the first hour of dosing (10 mg [75.5%, p<0.0001], 20 mg [69.1%, p = 0.0010], 40 mg [75.5%, p<0.0001], placebo [57.0%]).Over 90% of heartburn episodes treated with VOQUEZNA improved within two hours. Non-Erosive GERD is the largest category of GERD and is characterized by reflux-related symptoms in the absence of esophageal mucosal erosions. An estimated 45 million U.S. adults are living with Non-Erosive GERD, and approximately 15 million are treated with a prescription medicine annually. Despite longstanding treatment options, many patients continue to suffer from heartburn symptoms. As Needed dosing is a unique and differentiated dosing regimen for which proton pump inhibitors (PPIs), a mainstay of GERD treatment, are not approved in the U.S.5 In July 2024, VOQUEZNA was approved by the FDA as a daily dosing treatment for the relief of heartburn associated with Non-Erosive GERD in adults.1 Nocturnal GERD Symptoms in Non-Erosive GERD6 In a poster presentation on Monday, October 28 at ACG, which has received ACG’s Presidential Poster Award, Dr. Catiele Antunes, M.D., Yale New Haven Hospital, will present data looking at the common, yet infrequently evaluated, nocturnal symptoms among patients with Non-Erosive GERD. The study included an exploratory analysis of a validated patient-reported outcomes scale, the Nocturnal Gastro-esophageal reflux disease Symptom Severity and Impact Questionnaire (N-GSSIQ), to determine the severity, morning impact, and concern about nocturnal GERD. “We are very pleased to continue to add to the body of clinical research evaluating the potential benefits of VOQUEZNA for GERD patients,” said Eckhard Leifke, M.D., Chief Medical Officer at Phathom. “In our study, patients who experienced nocturnal GERD symptoms prior to VOQUEZNA treatment found effective and meaningful relief with daily dosing, reinforcing its potent and durable acid suppression profile in helping to address both daytime and nighttime heartburn. While these findings are exploratory, they show promise for the many individuals suffering from nocturnal GERD symptoms.” Results:6 Among 772 subjects, the mean percentage of heartburn-free nights during the screening period was 29.6%, 25.8% and 31.1%, for patients randomized to placebo, VOQUEZNA 10 mg and 20 mg, respectively.After 4 weeks, the least-square (LS) mean percentage of heartburn-free nights was significantly better with 59.9% for VOQUEZNA 10 mg (LS mean difference=16.5%, p<0.0001 vs. placebo), and 56.4% for VOQUEZNA 20 mg (LS mean difference=13.1%, p<0.0001 vs. placebo), compared to 43.3% for placebo. The median percentage of heartburn-free nights was 70.4% for VOQUEZNA 10 mg and 71.0% for VOQUEZNA 20 mg, compared to 45.5% for placebo.N-GSSIQ scores showed significant improvement with VOQUEZNA compared to placebo in total score (LS mean difference vs. placebo of -2.9 and -1.8 for VOQUEZNA 10 mg and 20 mg, respectively; p<0.005 for both comparisons), nocturnal symptom severity (LS mean difference vs. placebo of -5.4 and -3.5 for VOQUEZNA 10 mg and 20 mg; p<0.001 for both comparisons), and concern about nocturnal GERD (LS mean difference vs. placebo of -2.0 for both VOQUEZNA 10 mg and 20 mg; p<0.0001). In addition to these data presentations, Phathom will sponsor a product theater highlighting VOQUEZNA as an approved treatment for GERD and will also have a presence on the exhibit floor at booth #757 throughout the conference. Following the conclusion of ACG 2024, the abstracts will be posted to the publications and scientific section of the Phathom company website. VOQUEZNA is marketed exclusively by Phathom Pharmaceuticals, Inc. and is currently available via prescription. Please visit voqueznapro.com to learn more about VOQUEZNA. About Non-Erosive Gastroesophageal Reflux DiseaseNon-Erosive GERD is the largest category of GERD and is characterized by reflux-related symptoms in the absence of esophageal mucosal erosions. There are over 65 million U.S. patients living with GERD, and it is estimated that approximately 70% of this population have Non-Erosive GERD. Symptoms of Non-Erosive GERD may impact overall quality of life and can include episodic heartburn, especially at night, regurgitation, problems swallowing, and chest pain.7,8 About VOQUEZNA®VOQUEZNA® (vonoprazan) tablets contain vonoprazan, an oral small molecule potassium-competitive acid blocker (PCAB). PCABs are a novel class of medicines that block acid secretion in the stomach. VOQUEZNA is approved in the U.S. for the treatment of adults with Erosive Esophagitis, also known as Erosive GERD, the relief of heartburn associated with Erosive GERD, the relief of heartburn associated with Non-Erosive GERD, and for the treatment of H. pylori infection in combination with either amoxicillin or amoxicillin and clarithromycin. Phathom in-licensed the U.S. rights to vonoprazan from Takeda, which markets the product in Japan and numerous other countries in Asia and Latin America. About Phathom Pharmaceuticals, Inc.Phathom Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel treatments for gastrointestinal diseases. Phathom has in-licensed the exclusive rights to vonoprazan, a first-in-class potassium-competitive acid blocker (PCAB) that is currently marketed in the United States as VOQUEZNA® (vonoprazan) tablets for the treatment of heartburn associated with Non-Erosive GERD in adults, the healing and maintenance of healing of Erosive GERD in adults and associated heartburn, in addition to VOQUEZNA® TRIPLE PAK® (vonoprazan tablets, amoxicillin capsules, clarithromycin tablets) and VOQUEZNA® DUAL PAK® (vonoprazan tablets, amoxicillin capsules) for the treatment of H. pylori infection in adults. For more information about Phathom, visit the company’s website at www.phathompharma.com and follow on LinkedIn and X. INDICATIONS AND USAGE VOQUEZNA® (vonoprazan) is a potassium-competitive acid blocker (PCAB) indicated in adults: for the healing of all grades of Erosive Esophagitis (Erosive Gastroesophageal Reflux Disease or Erosive GERD) and relief of heartburn associated with Erosive GERD.to maintain healing of all grades of Erosive GERD and relief of heartburn associated with Erosive GERD.for the relief of heartburn associated with Non-Erosive GERD.in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori (H. pylori) infection.in combination with amoxicillin for the treatment of H. pylori infection. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS VOQUEZNA is contraindicated in patients with a known hypersensitivity to vonoprazan or any component of VOQUEZNA, or in patients receiving rilpivirine-containing products. For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with VOQUEZNA, refer to the Contraindications section of the corresponding prescribing information. WARNINGS AND PRECAUTIONS Presence of Gastric Malignancy: In adults, symptomatic response to therapy with VOQUEZNA does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in patients who have a suboptimal response or an early symptomatic relapse after completing treatment with VOQUEZNA. In older patients, also consider endoscopy. Acute Tubulointerstitial Nephritis: Acute tubulointerstitial nephritis (TIN) has been reported with VOQUEZNA. If suspected, discontinue VOQUEZNA and evaluate patients with suspected acute TIN. Clostridioides difficile-Associated Diarrhea: Published observational studies suggest that proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridioides difficile-associated diarrhea (CDAD), especially in hospitalized patients. VOQUEZNA may also increase the risk of CDAD. Consider CDAD in patients with diarrhea that does not improve. Use the shortest duration of VOQUEZNA appropriate to the condition being treated. CDAD has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with VOQUEZNA, refer to Warnings and Precautions section of the corresponding prescribing information. Bone Fracture: Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, especially in patients receiving high dose (multiple daily doses) and long-term therapy (a year or longer). Bone fracture, including osteoporosis-related fracture, has also been reported with vonoprazan. Use the shortest duration of VOQUEZNA appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines. Severe Cutaneous Adverse Reactions (SCAR): Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with VOQUEZNA. Discontinue VOQUEZNA at the first signs or symptoms of SCAR or other signs of hypersensitivity and consider further evaluation. Vitamin B12 (Cobalamin) Deficiency: Long-term use of acid-suppressing drugs can lead to malabsorption of Vitamin B12 caused by hypo- or achlorhydria. Vitamin B12 deficiency has been reported postmarketing with vonoprazan. If clinical symptoms consistent with vitamin B12 deficiency are observed in patients treated with VOQUEZNA, consider further workup. Hypomagnesemia and Mineral Metabolism: Hypomagnesemia has been reported postmarketing with vonoprazan. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. Consider monitoring magnesium levels prior to initiation of VOQUEZNA and periodically in patients expected to be on prolonged treatment, in patients taking drugs that may have increased toxicity in the presence of hypomagnesemia or drugs that may cause hypomagnesemia. Treatment of hypomagnesemia may require magnesium replacement and discontinuation of VOQUEZNA. Consider monitoring magnesium and calcium levels prior to initiation of VOQUEZNA and periodically while on treatment in patients with a preexisting risk of hypocalcemia. Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing VOQUEZNA. 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. Temporarily discontinue VOQUEZNA treatment at least 4 weeks before assessing CgA levels and consider repeating the test if initial CgA levels are high. Fundic Gland Polyps: Use of VOQUEZNA is associated with a risk of fundic gland polyps that increases with long-term use, especially beyond one year. Fundic gland polyps have been reported with vonoprazan in clinical trials and during postmarketing use with PPIs. Most patients who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of VOQUEZNA appropriate to the condition being treated. ADVERSE REACTIONS: Healing of Erosive GERD: The most common adverse reactions (≥2% of patients in the VOQUEZNA arm) include gastritis (3%), diarrhea (2%), abdominal distention (2%), abdominal pain (2%), and nausea (2%). Maintenance of Healed Erosive GERD: The most common adverse reactions (≥3% of patients in the VOQUEZNA arm) include gastritis (6%), abdominal pain (4%), dyspepsia (4%), hypertension (3%), and urinary tract infection (3%). Relief of Heartburn Associated with Non-Erosive GERD: The most common adverse reactions (≥2% of patients in the VOQUEZNA arm) include abdominal pain (2%), constipation (2%), diarrhea (2%), nausea (2%), and urinary tract infection (2%). Treatment of H. Pylori Infection (VOQUEZNA and Amoxicillin): The most common adverse reactions (≥2% in any treatment arm) include diarrhea (5%), abdominal pain (3%), vulvovaginal candidiasis (2%), nasopharyngitis (2%), dysgeusia (1%), headache (1%), and hypertension (1%). Treatment of H. Pylori Infection (VOQUEZNA, Amoxicillin and Clarithromycin): The most common adverse reactions (≥2% in any treatment arm) include dysgeusia (5%), diarrhea (4%), vulvovaginal candidiasis (3%), headache (3%), abdominal pain (2%), hypertension (2%), and nasopharyngitis (<1%). For more information on adverse reactions and laboratory changes with amoxicillin or clarithromycin, refer to Adverse Reactions section of the corresponding prescribing information. DRUG INTERACTIONS VOQUEZNA has the potential for clinically important drug interactions, including interactions with drugs dependent on gastric pH for absorption, drugs that are substrates for certain CYP enzymes, and some diagnostic tests. Avoid concomitant use of VOQUEZNA with atazanavir or nelfinavir. See full Prescribing Information for more details about important drug interactions. Consult the labeling of concomitantly used drugs to obtain further information about interactions with vonoprazan. For information about drug interactions, contraindications, and warnings and precautions of antibacterial agents (amoxicillin or clarithromycin) indicated in combination with VOQUEZNA, refer to their corresponding prescribing information. USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding is not recommended during treatment. Because of the potential risk of adverse liver effects shown in animal studies with vonoprazan, advise patients not to breastfeed during treatment with VOQUEZNA. Renal Impairment: For the healing of Erosive GERD, dosage reduction is recommended in patients with severe renal impairment (eGFR < 30 mL/min). Use of VOQUEZNA is not recommended for the treatment of H. pylori infection in patients with severe renal impairment. Hepatic Impairment: For the healing of Erosive GERD, dosage reduction is recommended in patients with moderate to severe hepatic impairment (Child-Pugh Class B and C). Use of VOQUEZNA is not recommended for the treatment of H. pylori infection in patients with moderate to severe hepatic impairment. 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. Forward-Looking StatementsThis press release contains forward-looking statements. Words such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or continue” and similar expressions, are intended to identify forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the ability of vonoprazan to relieve symptoms of GERD following As Needed dosing and to suppress nocturnal symptoms among patients with Non-Erosive GERD. 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: additional data related to vonoprazan to relieve symptoms of GERD following As Needed dosing may be inconsistent with the data produced as of the date hereof, and further analysis of existing data and analysis of new data may lead to conclusions different from those established as of the date hereof; 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; 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 and non-patent regulatory exclusivity for vonoprazan; Phathom’s estimates regarding patient population and commercial coverage could prove to be inaccurate; 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 most recent 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. References VOQUEZNA. Prescribing Information. Phathom Pharmaceuticals; 2024.Data on file. Phathom Pharmaceuticals, Inc. Florham Park, NJFass R, et al. Heartburn Frequency and Symptom Improvement Rates of Treated Episodes when Switching From Daily to On-Demand Vonoprazan Treatment for Non-Erosive Reflux Disease; American College of Gastroenterology (ACG) 2024 abstract; October 25-30, Philadelphia, PA.Fass R, Vaezi M, Sharma P, et al. Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease. Accessed September 17, 2024. Available at: https://doi-org.libproxy1.nus.edu.sg/10.1111/apt.17728Antunes C, Aleem A, Curtis SA. Gastroesophageal reflux disease. NCBI Bookshelf. Accessed January 21, 2024. Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/books/NBK441938/?report=printableAntunes C, et al. Vonoprazan Improves Nocturnal Gastroesophageal Reflux Symptoms in Non-Erosive Reflux Disease; American College of Gastroenterology (ACG) 2024 abstract; October 25-30, Philadelphia, PA.Machiacado JD, Greer JB, Yadav D. (2021) Epidemiology of Gastrointestinal Diseases. In: Pitchumoni CS, Dharmarajan T, (eds). Geriatric Gastroenterology. Springer, Cham. https://doi-org.libproxy1.nus.edu.sg/10.1007/978-3-030-30192-7_7Antunes C, Aleem A, Curtis SA. Gastroesophageal reflux disease. NCBI Bookshelf. Accessed January 21, 2024. Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/books/NBK441938/?report=printable MEDIA CONTACTNick Benedetto1-877-742-8466media@phathompharma.com INVESTOR CONTACTEric Sciorilli1-877-742-8466ir@phathompharma.com © 2024 Phathom Pharmaceuticals. All rights reserved.VOQUEZNA, VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK, Phathom Pharmaceuticals, and their respective logos are registered trademarks of Phathom Pharmaceuticals, Inc. 10/24US-VPZ-24-0557