Phathom Pharmaceuticals Announces FDA Acceptance for Filing of VOQUEZNA® (vonoprazan) Tablets New Drug Application for the Treatment of Heartburn Associated with Non-Erosive GERD
- New drug application (NDA) seeks U.S. Food and Drug Administration (FDA) approval for VOQUEZNA® as a daily treatment for heartburn associated with Non-Erosive GERD, the largest subcategory of GERD
- July 19, 2024 PDUFA target action date assigned by the FDA
FLORHAM PARK, N.J., Dec. 06, 2023 (GLOBE NEWSWIRE) -- Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal diseases, announced today the FDA has accepted for review the company’s NDA for VOQUEZNA (vonoprazan) as a daily treatment of heartburn associated with Non-Erosive gastroesophageal reflux disease (GERD) in adults. The FDA has assigned the application a standard 10-month review with a Prescription Drug User Fee Act (PDUFA) target action date of July 19, 2024.
"Today marks an important step forward for Phathom Pharmaceuticals as we announce the FDA's acceptance for filing of our New Drug Application for VOQUEZNA as a daily treatment of heartburn for patients with Non-Erosive GERD,” said Azmi Nabulsi, M.D., Chief Operating Officer at Phathom. “Non-Erosive GERD represents a substantial segment of the U.S. GERD population, affecting millions of individuals and impacting their quality of life. The supportive data in our regulatory application include the positive Phase 3 results from the investigational PHALCON-NERD-301 trial, along with a safety profile consistent with prior studies. We look forward to working closely with the FDA throughout the review process and if approved, expect to launch VOQUEZNA for this new indication in the third quarter of 2024.”
Non-Erosive GERD is the largest subcategory of GERD and is characterized by reflux-related symptoms in the absence of esophageal mucosal erosions. There are an estimated 38 million U.S. adults living with Non-Erosive GERD, of these approximately 15 million are diagnosed and treated with a prescription medicine annually. Symptoms impact overall quality of life and can include episodic heartburn, especially at night, regurgitation, problems swallowing, and chest pain.
Phathom is also finalizing its plans to initiate an additional Phase 3 study in 2024 evaluating VOQUEZNA as an investigational As Needed treatment for episodic heartburn relief in adults with Non-Erosive GERD, a novel dosing treatment regimen for which proton pump inhibitors (PPIs) are not approved in the U.S.
INDICATIONS AND USAGE
VOQUEZNA® (vonoprazan) is a potassium-competitive acid blocker (PCAB) indicated:
- for the healing of all grades of Erosive Esophagitis (Erosive Gastroesophageal Reflux Disease or Erosive GERD) and relief of heartburn associated with Erosive GERD in adults.
- for the maintenance of healing of all grades of Erosive GERD and relief of heartburn associated with Erosive GERD in adults.
IMPORTANT SAFETY INFORMATION
VOQUEZNA is contraindicated in patients with a known hypersensitivity to vonoprazan or any component of VOQUEZNA, or in patients receiving rilpivirine-containing products.
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.
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 14 days 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.
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%).
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.
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).
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).
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.
PHALCON-NERD-301 was a randomized, placebo-controlled, double-blind, multicenter Phase 3 study that enrolled 772 adult patients with symptomatic Non-Erosive GERD in the U.S. The trial evaluated the efficacy of VOQUEZNA 10 mg and 20 mg as a daily dosing (QD) treatment, as compared to placebo (QD), in the relief of heartburn over four weeks in participants with symptomatic Non-Erosive GERD. The trial also included a 20-week blinded long-term extension period to further evaluate the safety and efficacy of both doses of VOQUEZNA after six months of continuous use.
VOQUEZNA® (vonoprazan) tablets contain vonoprazan, an oral small molecule potassium-competitive acid blocker (PCAB), approved in the U.S. for the treatment of adults with Erosive Esophagitis, also known as Erosive GERD, and the relief of heartburn associated with Erosive GERD. PCABs are a novel class of medicines that block acid secretion in the stomach. Phathom in-licensed the U.S., European, and Canadian 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 in the U.S., Europe, and Canada to vonoprazan, a first-in-class potassium-competitive acid blocker (PCAB). For more information about Phathom, visit the Company’s website at www.phathompharma.com and follow the Company on LinkedIn and X (formerly Twitter).
This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the timing of regulatory approval and launch of VOQUEZNA for the treatment of heartburn associated with Non-Erosive GERD, initiation of a Phase 3 trial evaluating VOQUEZNA as an As Needed treatment of heartburn associated with Non-Erosive GERD, and the size of the Non-Erosive GERD patient population. 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: we may not be able to successfully commercialize VOQUEZNA which will depend on a number of factors including coverage and reimbursement levels from governmental authorities and health insurers as well as market acceptance by healthcare providers; future data generated from our stability program may be different from the data submitted to the FDA to date and may not demonstrate that our mitigation efforts will continue to maintain the level of the nitrosamine impurity below the acceptable intake (AI) level throughout the shelf life of products containing vonoprazan, which could result in market action or shelf life reduction; risks associated with product manufacturing or formulation changes required to be made in connection with achieving the AI; 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 access additional capital under its term loan facility and royalty interest finance agreements is subject to certain conditions; Phathom’s ability to obtain and maintain intellectual property protection for vonoprazan; Phathom’s ability to comply with its license agreement with Takeda; 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.
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