Ibsrela (tenapanor) / Ardelyx, Kyowa Kirin, Fosun Pharma, Knight Therap - LARVOL DELTA

Ardelyx Announces Three Abstracts Accepted for Poster Presentations at Digestive Disease Week 2025 Conference (GlobeNewswire) - "Ardelyx, Inc...today announced that the company will present data supporting the company’s first-in-class retainagogue, IBSRELA (tenapanor), as well as results from the IBS in America 2024 supplemental survey, at the upcoming Digestive Disease Week Conference (DDW), to be held May 3-6, 2025, in San Diego. IBSRELA is approved by the U.S. Food and Drug Administration to treat irritable bowel syndrome with constipation (IBS-C) in adults."

Clinical data • Constipation • Gastrointestinal Disorder

Effect of Tenapanor on Serum Phosphorus (Pi), Creatinine (Cre), and Body Weight (BW) Gain in Hemodialysis Patients (ERA 2025) - No abstract available

Clinical • Renal Disease

Tenapanor administration combined with phosphate binders provides synergistic phosphate lowering effect (ERA 2025) - No abstract available

An update on investigation and management of renal bone disease. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "New pathways for phosphate control are continually being investigated, changing practice patterns and quality of life for patients. Further research is needed in the safety and efficacy of antiresorptive and stimulatory bone agents to target the variety of mechanisms of osteoporosis; however, small studies appear promising and could change the way these patient populations are treated."

Journal • Cardiovascular • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Orthopedics • Osteoporosis • Renal Disease • Rheumatology

Impact of Xphozah on phosphorus in an adult male on hemodialysis (NKF-SCM 2025) - "PO4 levels decreased when the patient was adherent to both Xphozah and PO4 binder with no changes in dietary habits.Conclusion This case demonstrates that Xphozah was an effective intervention in reducing PO4 levels in an adult on HD when other extensive interventions with diet, nutritional counseling, and titration of various PO4 binders were ineffective. These findings are of value to renal dietitians as this is a new medication that is not yet widely utilized and may be an appropriate treatment option for patients with chronically high PO4 levels when other nutritional and medication interventions have failed."

Clinical • Chronic Kidney Disease • Nephrology • Renal Disease

Tenapanor-Treated Patients Using Over-the-Counter Antidiarrheal Agents Saw Decreased Stool Frequency and Improved Stool Consistency (NKF-SCM 2025) - "In the frequent BM subgroup, the mean (SD) AWSF decreased from 16.9 (5.3) to 13.6 (6.6). In the soft stool subgroup, average weekly stool consistency score improved from a mean (SD) of 6.6 (0.3) to 6.0 (0.9).Conclusion Loperamide is a treatment option to ameliorate diarrhea emergent with tenapanor treatment."

Clinical • Chronic Kidney Disease

Management of serum phosphorus over six months in hemodialysis patients: a comparison of sucroferric oxyhydroxide (SO) monotherapy and tenapanor with other non-SO phosphate binders (NKF-SCM 2025) - "However, the SO group had fewer pills (4.7 pills for SO vs 9.7 pills for +TN group at M6), and less diarrhea during fup (20.4% at bl, 23.9% at fup, p=0.19 for SO group; 21.9% at bl, 33.9% at fup, p=0.01 for +TN group).Conclusion For HD pts with sP > 7 mg/dL despite treatment with non-SO monotherapy, switching to SO monotherapy or adding TN resulted in comparable sP reductions, over 6 months. However, pts on SO monotherapy had less than half the PB pill burden, and lower % of diarrhea, compared to those adding TN."

Clinical • Monotherapy • Metabolic Disorders • Nephrology • Renal Disease

Efficacy and Safety of Phosphate-Lowering Agents for Adult Patients with Chronic Kidney Disease Requiring Dialysis: A Network Meta-Analysis. (PubMed, Clin J Am Soc Nephrol) - "Compared with calcium-based agents, sevelamer was associated with lower all-cause mortality, and sucroferric oxyhydroxide and lanthanum were associated with slower progression of CACS. Potential benefits and harms should be considered when selecting phosphate-lowering agents (PROSPERO: CRD42022328388)."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Gastrointestinal Disorder • Musculoskeletal Diseases • Nephrology • Renal Disease

NEITHER TENAPANOR NOR ITS MAJOR METABOLITE WERE DETECTED IN THE BREAST MILK OF HEALTHY LACTATING FEMALES AFTER 4 DAYS OF DOSING: A PHASE 1, OPEN-LABEL, PHARMACOKINETIC STUDY (DDW 2025) - No abstract available

Clinical • P1 data • PK/PD data • Gastrointestinal Disorder

SAFETY AND TOLERABILITY OF TENAPANOR IN PEDIATRIC PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION: AN ANALYSIS OF BLINDED SAFETY DATA FROM A PHASE 3 STUDY AND ITS OPEN-LABEL EXTENSION (DDW 2025) - No abstract available

Clinical • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

Novel gut-restricted bivalent agonists targeting mucosal 5-HT4R: Design, synthesis, and biological evaluation. (PubMed, Eur J Med Chem) - "Herein, we report for the first time the rational design and synthesis of gut-restricted bivalent agonists targeting mucosal 5-HT4R by integrating pharmacophores of prucalopride and tenapanor. Preclinical studies demonstrated that compound 4 significantly enhanced whole-gut and colonic transit, increased fecal output and water content, while maintaining minimal systemic absorption, confirming its gut-restricted nature. These findings underscore the feasibility of gut-restricted 5-HT4R agonists as a novel therapeutic strategy for CIC and provide valuable insights into the development of safer, more effective treatments for gastrointestinal disorders."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Ardelyx Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "U.S. net product sales revenue for IBSRELA in 2024 was $158.3 million, including $53.8 million in net product sales revenue in the fourth quarter, approximately 32% growth compared to the third quarter of 2024. Ardelyx currently expects full year 2025 U.S. net product sales revenue for IBSRELA to be between $240 and $250 million...U.S. net product sales revenue for the first full calendar year of commercialization of XPHOZAH was $160.9 million, including $57.2 million in net product sales revenue during the fourth quarter of 2024. At peak, Ardelyx currently expects XPHOZAH to achieve $750 million in annual U.S. net product sales revenue before patent term expiration."

Sales • Sales projection • Chronic Kidney Disease • Constipation • Gastroenterology • Gastrointestinal Disorder • Renal Disease

High-salt diets provoke phosphorus absorption from the small intestine in mice. (PubMed, Clin Exp Hypertens) - "Recent studies indicate that tenapanor, an inhibitor of sodium/proton exchanger-3 (NHE3), diminishes intestinal phosphorus (Pi) absorption...HSD disrupts Pi metabolism by enhancing urinary Pi excretion and altering hormonal levels. The decrease in fecal Pi excretion, coupled with the upregulation of intestinal Pi transporter expression, suggests that HSD promotes intestinal Pi absorption in mice."

Journal • Preclinical • Anesthesia • FGF23

Tenapanor Approved in China for Hyperphosphatemia (GlobeNewswire) - "Ardelyx, Inc...today announced the approval of a New Drug Application (NDA) by China’s Center for Drug Evaluation of the National Medical Products Administration for tenapanor to control serum phosphorus levels in dialysis patients with chronic kidney disease (CKD) who have an inadequate response or are intolerant to phosphorus binders. This approval triggers a $5 million milestone payment to Ardelyx under the terms of the license agreement between Ardelyx...Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. (Fosun Pharma). Under the terms of its agreement, Ardelyx is eligible to receive additional developmental and commercialization milestones of up to $100 million and tiered royalty payments on net sales ranging from the mid-teens to 20 percent...The NDA in China was supported by data from two studies undertaken by Fosun Pharma, a single pharmacokinetic study and a single pivotal trial in patients with CKD on dialysis, in addition to Ardelyx clinical studies."

China approval • Financing • Chronic Kidney Disease

Tenapanor in Synucleinopathy-Related Constipation (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Cedar Valley Digestive Health Center | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Comparison chart: Safety of drugs for IBS in pregnancy and lactation. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Gastrointestinal Disorder

Drugs for irritable bowel syndrome. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Figure 1: Treatments for irritable bowel syndrome (IBS) in adults. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Comparison chart: Some drugs for irritable bowel syndrome with constipation (IBS-C). (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Assessing Tenapanor As a Treatment of CF-related Constipation. (clinicaltrials.gov) - P3 | N=25 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P3 trial • Constipation • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Combination Oxylanthanum Carbonate and Tenapanor Lowers Urinary Phosphate Excretion in Rats. (PubMed, Kidney360) - "In summary, we demonstrated sizeable reductions in urinary phosphate excretion in response to OLC monotherapy and the most pronounced reductions in urinary phosphate excretion when using OLC in combination with tenapanor."

Journal • Preclinical

Tenapanor: A novel therapeutic agent for dialysis patients with hyperphosphatemia. (PubMed, Ther Apher Dial) - "Four phase 3 studies of tenapanor have been performed in Japan and have demonstrated its efficacy and safety as a single-agent drug, add-on effects to PBs for patients with refractory hyperphosphatemia that cannot be improved with PBs alone, and reduction of the pill burden associated with PBs. This review provides an overview of the characteristics and previous clinical studies of tenapanor and describes the clinical benefits of tenapanor over current therapy in patients on dialysis."

Journal • Review • Cardiovascular • Metabolic Disorders • Nephrology • Renal Disease

Single-Center Experience with Concomitant Use of Novel and Off-Label Prescriptions for Chronic Constipation (ACG 2024) - "Charts were reviewed for prescriptions of at least 1 of 8 pharmacotherapies: linaclotide, lubiprostone , plecanatide , prucalopride, tenapanor , tegaserod, pyridostigmine, and colchicine. 405 patients were evaluated for chronic constipation, of which 138 (34%) received one or more prescription-based therapies. The most common diagnoses supporting these prescriptions are listed in Table 1. 110 patients (79.7%) were prescribed monotherapy, 23 (16.67%) given dual therapy simultaneously, 4 (2.8%) given three agents simultaneously, and only 1 (0.7%) given four agents simultaneously."

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

Efficacy and safety of tenapanor vs placebo in treating CKD patients on dialysis and with hyperphosphatemia: a systematic review and meta-analysis of 2251 patients. (PubMed, Int Urol Nephrol) - "Based on our meta-analysis, tenapanor can effectively reduce serum phosphate, iPTH, and sodium. Additionally, it improves bowel movement frequency and stool consistency. However, it is associated with a higher risk of GIT symptoms that should be considered and managed during treatment. We recommend conducting further RCTs to perform head-to-head comparisons against other active comparators such as phosphate binders."

Journal • Retrospective data • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Effectivity and safety profile of tenapanor, a sodium-hydrogen exchanger isoform 3 inhibitor, as an innovative treatment for hyperphosphatemia in chronic kidney disease: A systematic review of clinical studies. (PubMed, Nefrologia (Engl Ed)) - "Tenapanor is an effective and safe option for hyperphosphatemia management in CKD."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease • FGF23