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

Tenapanor: An Update on Evidence of Effectiveness and Guidance on Practical Use. (PubMed, Am J Kidney Dis) - "Tenapanor, a novel therapy that targets intestinal phosphate absorption, has shown promise in reducing serum phosphate both as monotherapy and in combination with binders, though gastrointestinal side effects may occur. Herein, we review the available information about the clinical use of Tenapanor, including its safety profile, and we provide some clinical suggestions for its practical use."

Journal • Metabolic Disorders • Nephrology • Renal Disease

FDA-approved drugs as potential covalent inhibitors of key SARS-CoV-2 proteins: an in silico approach. (PubMed, Turk J Biol) - "Several promising drug repurposing candidates were identified: bremelanotide, lanreotide, histrelin, and leuprolide as potential RdRp inhibitors; azlocillin, cefiderocol, and sultamicillin for Mpro inhibition; tenapanor, isavuconazonium, and ivosidenib targeting TMPRSS2; and cefiderocol, cefoperazone, and ceftolozane as potential ACE2 inhibitors. This study provides valuable insights into repurposing existing drugs as potential COVID-19 therapeutics by targeting crucial viral proteins. However, further experimental validation and preclinical studies are necessary to confirm the efficacy and safety of these compounds before consideration for clinical application."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: a systematic review and meta-analysis of short term randomized control trails. (PubMed, Am J Nephrol) - "In summary, the results indicate that tenapanor effectively lowers serum phosphate levels in haemodialysis patients and facilitates achievement of target levels, although drug-related side effects were common. However, these findings are based exclusively on short-term trials (4-8 weeks). Further long-term studies are needed to confirm the sustained efficacy and safety of tenapanor."

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

YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer in mice. (PubMed, Nat Commun) - "Either myeloid-specific conditional knockout of YY1 or a treatment with tenapanor for decreasing the YY1-NUSAP1-HIF-1α interaction impairs subcutaneous PCa tumor formation in mouse prostate tumor models. Lastly, a first-generation tetrahedral DNA nanostructure based on the proteolysis targeting chimera technique, termed YY1-DcTAC, allows targeting and degrading YY1 in tumor-associated macrophages for inducing antitumor effects and CD8+ T cell tumor infiltration in mouse tumor models. In summary, our findings underscore the pivotal role of YY1 in the hypoxia/HIF-1α pathway in tumor-associated macrophages and support the targeting of YY1 for treating PCa."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • CD8 • HIF1A • NUSAP1 • YY1

The Positive Impact of Patient Education on Tenapanor Adherence in the OPTIMIZE Study. (PubMed, Nephrol Nurs J) - "In all studies, most diarrhea episodes (88.7% to 91.9%) were mild/moderate; the majority (75.7% to 79.6%) occurred within weeks 1 and 2. Patient education may help improve tenapanor adherence and reduce the incidence of bothersome loose stools."

Journal • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease

Efficacy of tenapanor in managing hyperphosphatemia and constipation in hemodialysis patients: A randomized controlled trial. (PubMed, PLoS One) - "Tenapanor improves stool consistency, reduces laxative use, and provides effective phosphorus control in hemodialysis patients and represents a promising alternative to conventional phosphate binders."

Clinical • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease

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

Enrollment open • Constipation • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

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