NHE3

WALTHAM, Mass., July 31, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced the publication of plain language summaries of results from two clinical trials on XPHOZAH® (tenapanor), NORMALIZE and OPTIMIZE, in Current Medical Research and Opinion. The plain language summaries were developed by the authors to help adult patients with chronic kidney disease receiving dialysis, and their family members and caregivers, better understand some of the safety and efficacy data related to XPHOZAH. XPHOZAH, the first and only phosphate absorption inhibitor (PAI), is approved by the U.S. Food and Drug Administration to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. XPHOZAH offers a different mechanism of action, blocking phosphate absorption at the primary pathway and is administered as a single tablet taken twice daily. “We are proud to provide the clinical trials results for both the NORMALIZE and OPTIMIZE studies to patients in a format that is both useful and relevant to their needs. Plain language summaries, like these, help patients and their caregivers better understand their options and the potential impact XPHOZAH may have on lowering their serum phosphorus levels,” said Laura Williams, MD MPH, chief medical officer of Ardelyx. “Our entire Ardelyx team would like to express our gratitude to the patients who participated in these clinical trials, whose contributions are now helping other patients better understand the complications associated with elevated serum phosphorus and this new treatment option. We would also like to recognize the study authors who worked with our partners in the patient advocacy community to ensure that these plain language summaries could be made available to our patients.” Current Medical Research and Opinion is an international journal that publishes research focused on new and existing drugs and therapies, best practices in patient care, developments in diagnostic medicine and medical technology, and innovations in medical and scientific publishing. The first article, titled “Tenapanor improves long-term control of high phosphate concentrations in the blood in patients receiving maintenance dialysis: a plain language summary of the NORMALIZE study,” describes results from the NORMALIZE study, is available online and can be found here. The second article, titled “Effectiveness of tenapanor for treating hyperphosphatemia in patients receiving dialysis: a plain language summary of the OPTIMIZE study” provides a review of the OPTIMIZE study, is available online and can be found here. Both articles are summaries of data originally published in Kidney360. About XPHOZAH® (tenapanor)XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information. About NORMALIZE Patients completing the Phase 3 PHREEDOM trial from both the XPHOZAH arm and the sevelamer safety control arm had the option to participate in NORMALIZE, an open-label 18-month extension study. Patients entering the study from the XPHOZAH arm with serum phosphate levels in the normal range were followed with no medication changes. Patients entering the study from the XPHOZAH arm with serum phosphate greater than 4.5 mg/dL had sevelamer tablets added incrementally to achieve normal serum phosphate levels. Patients entering the study from the sevelamer safety control arm had XPHOZAH tablets added to their treatment regimen while reducing sevelamer tablets based on their serum phosphate value to achieve normal serum phosphate levels. The primary objective of the study was to evaluate the ability of XPHOZAH alone or in combination with sevelamer to achieve serum phosphate levels within the normal range (2.5 to 4.5 mg/dL) in patients with CKD on maintenance dialysis whose serum phosphate levels were greater than 6.0 mg/dL at baseline. About OPTIMIZEOPTIMIZE was a randomized, open label study, which included 330 patients with chronic kidney disease (CKD) on dialysis with hyperphosphatemia. The study was designed to evaluate different methods of initiating XPHOZAH to optimize phosphorus management in both binder-naïve and binder-treated patients. The objective was to evaluate the ability of XPHOZAH, with its novel blocking mechanism, administered as core therapy for the treatment of hyperphosphatemia in adult patients with chronic kidney disease (CKD) on dialysis, alone or in combination with phosphate binders, to achieve target serum phosphorus (s-P) levels ≤5.5 mg/dL. The study enrolled patients with s-P >5.5 and ≤10.0 mg/dL during stable phosphate binder treatment which were randomized in a 1:1 ratio to two different treatment cohorts, as well as patients who were phosphate binder naïve with s-P >4.5 and ≤10.0 mg/dL in a third cohort. About HyperphosphatemiaHyperphosphatemia is a serious condition, defined as elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONSXPHOZAH is contraindicated in: Pediatric patients under 6 years of agePatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSDiarrhea Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea. MOST COMMON ADVERSE REACTIONS Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials. INDICATION XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. For additional safety information, please see full Prescribing Information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com

Lawsuit challenges CMS’s statutory overreach in its determination to include oral-only phosphate-lowering therapies in the End-Stage Renal Disease Prospective Payment System Inclusion of oral-only phosphate lowering therapies within the ESRD PPS limits patient choice and timely access to important innovations and treatment options for unmet needs WALTHAM, Mass., July 17, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced that, in partnership with the American Association of Kidney Patients (AAKP), the nation’s largest independent kidney patient organization, and the National Minority Quality Forum (NMQF), the nation's largest minority healthcare research, education and advocacy organization, it has filed a lawsuit against the U.S. Department of Health and Human Services and the Centers for Medicare and Medicaid Services (CMS), claiming that CMS’s plan to include XPHOZAH® (tenapanor), along with all other oral-only phosphate lowering therapies (PLTs), in the End-Stage Renal Disease Prospective Payment System (ESRD PPS) will significantly and negatively impact patient choice of and timely access to important medications. The lawsuit claims that CMS has violated its statutory and regulatory authority under the Medicare Improvements for Patients and Providers Act (MIPPA), which established the ESRD PPS bundled payment system for dialysis services in 2008. Specifically, the lawsuit claims that CMS’s plan to move XPHOZAH, along with all oral-only PLTs, into the ESRD PPS is inconsistent with MIPPA’s statutory provision, and contradicts CMS’s own regulations. XPHOZAH and other PLTs, which are currently available to patients under outpatient pharmacy benefit plans such as Medicare Part D, are not administered by dialysis providers and cannot be taken during the delivery of maintenance dialysis. The plaintiffs seek relief under the Administrative Procedure Act to enjoin CMS from proceeding with its plan to include XPHOZAH in the ESRD PPS and eliminate coverage under Medicare Part D beginning on January 1, 2025. “It is abundantly clear that moving XPHOZAH and other PLTs into the ESRD PPS will result in the imposition of severe care choice and timely access restrictions for all dialysis patients. The planned move by CMS will continue to create disincentives for the development of new and important medicines that can improve patient health and address unmet needs in an already underserved therapeautic area,” said Mike Raab, president and chief executive officer of Ardelyx. “In the eight months that our first-in-class phosphate absorption inhibitor, XPHOZAH, has been in clinical use, many patients have now been able to achieve and maintain phosphorus levels within the target range. Patients with elevated phosphorus have few options to improve their condition and are now at risk of losing choice and timely access to a brand new, FDA-approved therapy that is providing them a meaningful clinical benefit. This lawsuit attempts to stop CMS’s continued harmful statutory overreach and better protect dialysis patients’ choice and timely access to important new therapies.” XPHOZAH was approved by the U.S. Food and Drug Administration in October 2023 to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. Eighty percent of patients with CKD on dialysis require prescription therapy to lower elevated levels of serum phosphorus. Phosphate binders are not sufficient for a majority of patients to achieve and maintain phosphorus levels within target range. XPHOZAH is a single tablet taken twice daily that offers a first-in-class mechanism of action that blocks phosphate absorption through its primary pathway. About XPHOZAH® (tenapanor)XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information. About HyperphosphatemiaHyperphosphatemia is a serious condition, defined as elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL). IMPORTANT SAFETY INFORMATION (XPHOZAH) CONTRAINDICATIONS XPHOZAH is contraindicated in: Pediatric patients under 6 years of agePatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSDiarrhea Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea. MOST COMMON ADVERSE REACTIONS Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials. INDICATION XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. For additional safety information, please see full Prescribing Information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. About the American Association of Kidney Patients (AAKP) Since 1969, AAKP has been a patient-led organization driving policy discussions on kidney patient care choice and medical innovations to improve patient lives and prevent avoidable illness and death. AAKP advocates played a central role in the Congressional authorization of the modern ESRD program and coverage for dialysis and transplantation. Over the past decade, AAKP patient advocates have helped advance lifetime transplant drug coverage for kidney transplant recipients (2020); the presidential Executive Order on Advancing American Kidney Health (2019); new job protections for living organ donors under the Family Medical Leave Act (FMLA) via the U.S. Department of Labor (2018); and Congressional legislation allowing HIV-positive organ transplants for HIV-positive patients (2013). Follow AAKP on social media at @kidneypatient on Facebook, @kidneypatients on Twitter, and @kidneypatients on Instagram, and visit http://www.aakp.org for more information. About National Minority Quality ForumThe National Minority Quality Forum (NMQF) is a 501(c)(3) not-for-profit research and advocacy organization based in Washington, DC. The mission of NMQF is to reduce patient risk by assuring optimal care for all. NMQF’s vision is an American health services research, delivery and financing system whose operating principle is to reduce patient risk for amenable morbidity and mortality while improving quality of life. For more information, please visit www.nmqf.org. Forward Looking Statements To the extent that statements contained in this press release are not descriptions of historical facts regarding Ardelyx, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor of the Private Securities Reform Act of 1995, including the impact that moving XPHOZAH and PLTs into the ESRD PPS will have on patient access and the clinical benefit of XPHOZAH. Such forward-looking statements involve substantial risks and uncertainties that could cause Ardelyx's future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, uncertainties associated with the development of, regulatory process for, and commercialization of drugs in the U.S. and internationally. Ardelyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ardelyx's business in general, please refer to Ardelyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 2, 2024, and its future current and periodic reports to be filed with the Securities and Exchange Commission. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com

Ardelyx continues support for bipartisan legislation that would extend the exclusion of oral-only medications from entering the CMS Prospective Payment System Conference call scheduled for 8:00 AM Eastern Time WALTHAM, Mass., July 02, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced that, in an effort to preserve patient access to its phosphate absorption inhibitor XPHOZAH® (tenapanor), the Company has chosen not to apply to include XPHOZAH in the Centers for Medicare & Medicaid Services (CMS) End-Stage Renal Disease (ESRD) Prospective Payment System (PPS) Transitional Drug Add-on Payment Adjustment (TDAPA). Ardelyx’s analysis of the CMS policy to include oral-only medicines in the PPS and the Calendar Year 2025 ESRD PPS Proposed Rule released on June 27, 2024, revealed that the policy and the manner in which CMS intends to implement it are likely to cause significant restrictions on the use of XPHOZAH for all patients, irrespective of insurance coverage, because it interferes with the essential and appropriate shared decision-making between healthcare professionals and their patients. “At Ardelyx, we recognize that the only way innovative medicines like XPHOZAH can deliver their proven benefits to patients is by ensuring that those prescribed our medicines have access to them. XPHOZAH is the only therapy approved for patients who have an inadequate response to phosphate binder therapy and during the eight months it has been utilized in clinical practice, it is clear that patients are benefitting from and need continued access to this therapeutic option to reduce elevated serum phosphorus,” said Mike Raab, president and CEO of Ardelyx. “We have carefully and thoughtfully considered the potential impact of CMS’s decision to add XPHOZAH into the Medicare PPS and have determined that even during the TDAPA period, the restrictions placed on XPHOZAH would be such that patient access to this novel therapy would be effectively eliminated for all patients. We believe that the proposed bipartisan legislation extending the exclusion of oral-only medications from the Medicare ESRD PPS is the best option to ensure continued patient access, and we call on Congress to pass the bill. Our decision not to apply for TDAPA reflects our steadfast commitment to preserving patients’ access to our medicines and provides the best optionality for us to continue to explore alternatives to protect all patients.” XPHOZAH was approved by the U.S. Food and Drug Administration in October 2023 to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. Eighty percent of patients with CKD on dialysis require prescription therapy to lower elevated levels of serum phosphorus. Phosphate binders are not sufficient for a majority of patients to achieve and maintain phosphorus levels within target range. XPHOZAH is a single tablet taken twice daily that offers a first-in-class mechanism of action that blocks phosphate absorption through its primary pathway. Conference Call DetailsThe company will host a conference call today, July 2, 2024, at 8:00 am ET to discuss today's announcement. To participate in the conference call, please dial (844) 481-2838 (domestic) or (412) 317-1858 (international) and ask to be joined into the Ardelyx call. A webcast of the call can also be accessed by visiting the Investor page of the company's website, https://ardelyx.com/, and will be available on the website for 30 days following the call. About XPHOZAH® (tenapanor)XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information. About HyperphosphatemiaHyperphosphatemia is a serious condition, defined as resulting in elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL). IMPORTANT SAFETY INFORMATION (XPHOZAH) CONTRAINDICATIONS XPHOZAH is contraindicated in: Pediatric patients under 6 years of agePatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSDiarrhea Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea. MOST COMMON ADVERSE REACTIONS Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials. INDICATION XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. For additional safety information, please see full Prescribing Information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. Forward Looking StatementsTo the extent that statements contained in this press release are not descriptions of historical facts regarding Ardelyx, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor of the Private Securities Reform Act of 1995, including the impact of the TDAPA period and the ESRD PPS policy on access to XPHOZAH and our current belief that not applying for TDAPA provides the best optionality to explore options to provide access to all patients. Such forward-looking statements involve substantial risks and uncertainties that could cause Ardelyx's future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, uncertainties associated with the development of, regulatory process for, and commercialization of drugs in the U.S. and internationally. Ardelyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ardelyx's business in general, please refer to Ardelyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 2, 2024, and its future current and periodic reports to be filed with the Securities and Exchange Commission. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com