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

Constipation-predominant irritable bowel syndrome treatment options Linaclotide, Lubiprostone, plecanatide, and Tenapanor: analysis of the FDA adverse event reporting system (FAERS) database. (PubMed, Expert Opin Drug Saf) - "This post-marketing analysis of the FAERS database revealed diarrhea, abdominal pain, bloating, and nausea/vomiting were the most frequently reported AEs across all medications. Novel findings include the potential for clinically significant dehydration from Linaclotide-induced diarrhea and Lubiprostone-associated dyspnea and chest pain."

Adverse events • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Pulmonary Disease

Effect of Tenapanor on Serum Phosphorus (Pi), Creatinine (Cre), and Body Weight (BW) Gain in Hemodialysis Patients (ERA 2025) - "In HD patients, TENAP administration has been confirmed to stably lower serum Pi for a relatively long period. The decrease in Pi and the change in BW by TENAP administration have been suggested to be related to the inhibition of Na absorption by NHE3 in the gastrointestinal tract. It is also suggested that a decrease in Cre may occur in conjunction with a decrease in Pi, although the cause remains unknown."

Clinical • Chronic Kidney Disease • Constipation • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease

Tenapanor administration combined with phosphate binders provides synergistic phosphate lowering effect (ERA 2025) - "Six types of P binders had been used in Group Ad (sevelamer hydrochloride, bixalomer, calcium carbonate, ferric citrate, sucroferric oxyhydroxide hydrate and lanthanum carbonate hydrate). Oral administration of tenapanor significantly reduced P adsorption and improved serum P level in patients undergoing HD either when it was administrated alone or adding on P binders. This P absorption reduction effect of tenapanor was greatly enhanced when it was added on P binders. The mechanism of this synergistic effect would be an important research question."

Metabolic Disorders • Nephrology • Renal Disease

The Safety of Pharmacotherapy for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. (PubMed, Am J Gastroenterol) - "Among pharmacotherapies for IBS, tricyclics (especially at elevated doses), tenapanor, and alosetron have the highest absolute risk of discontinuation due to an AE when compared to rifaximin, the safest pharmacotherapy studied."

Journal • Retrospective data • Gastrointestinal Disorder

EVALUATING THE SAFETY OF PHARMACOTHERAPY FOR IRRITABLE BOWEL SYNDROME: A META-ANALYSIS (DDW 2025) - "AEs were more varied for tricyclics (indicated for IBS global symptoms); for example, compared to placebo the three most common AEs with associated risk increases were drowsiness (14%), dry mouth (12%), and weight gain (9%) for amitriptyline, dry mouth (22%), flushing (18%), and constipation (17%) for desipramine, and fatigue (15%), dry mouth (3%) and blurry vision (1.5%) for doxepin...The NNH for linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor (indicated for IBS-C) was 27 (p < 0.01), 53 (p = 0.59), 58 (p < 0.01), 59 (p = 0.03), and 17 (p <0.01) respectively. The NNH for alosetron and eluxadoline (indicated for IBS-D) was 16 (p < 0.01) and 32 (p < 0.01). Ramosetron and rifaximin (indicated for IBS-D) had a negative risk difference, with the rate of withdrawal due to AEs higher in the placebo arm, so NNH was a negative, although statistically insignificant, value... Tricyclics, alosetron, and tenapanor are associated with a higher..."

Retrospective data • Constipation • Fatigue • Gastrointestinal Disorder • Xerostomia

IBS-C PATIENT EXPERIENCES WITH PHARMACOLOGIC THERAPIES: QUALITATIVE ANALYSIS OF ONLINE POSTS FROM (TWITTER) AND E-HEALTH FORUMS (DDW 2025) - "To find relevant posts from IBS-specific subforums, we applied filters targeting FDA-approved IBS-C medications (linaclotide, lubiprostone, plecanatide, tegaserod, tenapanor). Discussions : Our study highlights the diverse real-world experiences of IBS-C patients with FDA-approved therapies, revealing variability in both efficacy and the biopsychosocial impacts associated with each medication. These findings highlight the importance of shared decision making in selecting an IBS-C treatment, including evaluating the need to switch medications or classes, as well as addressing barriers such as cost and side effects to improve adherence and patient outcomes."

Clinical • CNS Disorders • Constipation • Gastrointestinal Disorder • Mood Disorders • Psychiatry

Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management. (PubMed, Nutrients) - "Recently, tenapanor, an agent that blocks paracellular absorption of phosphate via inhibition of enteric sodium-hydrogen exchanger-3 (NHE3) was approved for the treatment of hyperphosphatemia in KF...Conceivably, deleterious effects associated with hyperphosphatemia could be attributable to disruptions in phosphorus-sensing mechanisms and hormonal imbalance thereof. Further exploration of mechanisms that precisely control phosphorus sensing and regulation may facilitate development of strategies to diminish the deleterious effects of phosphorus load and improve overall outcomes in KF."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Gastrointestinal Disorder • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease • FGF23

A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk. (clinicaltrials.gov) - P4 | N=10 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Nephrology • Renal Calculi

Assessing Tenapanor as a Treatment of CF-related Constipation. (clinicaltrials.gov) - P3 | N=25 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Initiation date: Feb 2025 ➔ Jun 2025

Trial initiation date • Constipation • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Dexamethasone disrupts intracellular pH homeostasis to delay coronavirus infectious bronchitis virus cell entry via sodium hydrogen exchanger 3 activation. (PubMed, J Virol) - "Also, Dex antiviral effects are relieved by the glucocorticoid receptor (GR) antagonist RU486 and the NHE3 selective inhibitor tenapanor. Dex activates NHE3, leading to an increase in intracellular pH and blocking the initiation of negative-stranded genomic RNA synthesis of coronavirus IBV. In this study, we identified the mechanism by which glucocorticoids counteract coronaviruses in cell models, laying the foundation for the development of novel antiviral drugs."

Journal • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

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) - "Tenapanor's efficacy and safety are currently being investigated in the R-ALLY study in pediatric patients with IBS-C. Preliminary safety results of this blinded study and its open-label safety extension are consistent with those from previous studies of tenapanor in adult patients with IBS-C. Diarrhea was the only adverse event related to study drug, which is consistent with tenapanor's mechanism of action."

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

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) - "Conclusions This study showed that tenapanor was not present at detectable levels in the breast milk of healthy lactating females after repeated oral administration. The safety profile of tenapanor was similar to that seen in previous clinical trials of healthy volunteers."

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

Pharmacologic Treatment of Irritable Bowel Syndrome with Predominant Constipation (PubMed, Korean J Gastroenterol) - "Guanylate cyclase-C agonists (linaclotide and plecanatide) enhance intestinal fluid secretion and motility, normalize bowel movements, and reduce abdominal pain. Na+/H+ exchanger inhibitors (e.g., tenapanor) decrease sodium absorption, increase fluid secretion, and alleviate visceral pain. Lubiprostone activates the chloride channels to facilitate bowel movements, while polyethylene glycol laxatives regulate osmotic pressure to improve stool consistency and ease defecation. Highly selective 5-HT4 agonists, such as prucalopride, accelerate gastrointestinal and colonic transit and improve stool frequency and consistency without increasing the cardiovascular risks raised in earlier agents such as tegaserod...These pharmacology agents have shown efficacy and safety in clinical studies, but drug availability, adverse effects, and variable patient responses are still challenging. Effective strategies to manage IBS-C require a personalized approach, considering the..."

Journal • Review • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Pain

MVP-LCN2 axis triggers evasion of ferroptosis to drive hepatocarcinogenesis and sorafenib resistance. (PubMed, Drug Resist Updat) - "Notably, tenapanor, a potent pharmacological inhibitor of MVP, effectively disrupts the interaction between MVP and LCN2 mRNA and enhances ferroptosis and sorafenib sensitivity. Collectively, these findings underscore the central role of MVP in hepatocarcinogenesis and offer promising avenues to improve HCC treatment."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • MVP • STAT3

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

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

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