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

First Reported Case of MRI Performed on a Patient With Multiple Vibrant Vibrating Capsules In Situ (ACG 2026) - "She experienced ineffective responses or side-effects to multiple pharmacologic therapies including polyethylene glycol, senna, bisacodyl (oral and rectal), glycerin suppositories, magnesium salts, linaclotide, plecanatide, lubiprostone, prucalopride, and tenapanor. This report also highlights the need for improved screening for ingestible electronic devices prior to MRI. Figure: X-ray Showing 5 Vibrant Vibrating Capsules In Situ 1 Day After MRI"

Clinical • Constipation • Endocrine Disorders • Fibromyalgia • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics

A Phase 3, 26-Week Randomized Controlled Study to Assess Safety and Efficacy of Tenapanor for Treatment of Chronic Idiopathic Constipation in Adults: Design and Rationale (ACG 2026) - P3 | "Approximately 692 participants will be enrolled across 90-120 US sites. The primary endpoint is the durable CSBM response, defined as achieving a weekly CSBM response for â¥9 out of the first 12 weeks, including â¥3 of the last 4 weeks. A weekly CSBM response was defined as an increase of â¥1 CSBM per week from baseline and an average of â¥3 CSBMs per week in a given week."

Clinical • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder

Health Care Resource Utilization Decreases Among Patients With Constipation Predominant Irritable Bowel Syndrome Following Initiation of Tenapanor: A Real-World Analysis (ACG 2026) - "The study included 470 tenapanor users. Pt characteristics were typical for pts with IBS-C ( Fig 1 ). GI-related HCRU decreased significantly post-tenapanor initiation vs the year prior (median [interquartile range] pre: 4.5 [2, 9], post: 3.0 [1, 6]; P < 0.001), driven mainly by reduced visits and labs."

Clinical • HEOR • Real-world • Real-world evidence • Back Pain • Bipolar Disorder • CNS Disorders • Constipation • Depression • Fibromyalgia • Gastroenterology • Gastrointestinal Disorder • Gynecology • Infectious Disease • Migraine • Mood Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Post-traumatic Stress Disorder

When Colitis Looks Like Cancer: Constipation-Predominant Ulcerative Colitis Mimicking Large Bowel Obstruction and Colorectal Malignancy (ACG 2026) - "Case Description/ A 70-year-old woman with UC on infliximab presented with two months of progressive constipation, hematochezia, abdominal pain, nausea, and vomiting refractory to six outpatient therapies including polyethylene glycol, linaclotide, tenapanor, laxatives, and enemas. Figure: CT abdomen/pelvis demonstrating left-sided colonic narrowing with proximal colonic dilation and fecal loading. Figure: Abdominal radiograph demonstrating persistent large colonic stool burden."

Colorectal Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Mucositis • Oncology • Ulcerative Colitis

Exhibitor Product Theater - Expanding IBS-C Care With a First-in-Class Treatment (ACG 2026) - "Aja McCutchen will review key IBSRELA information including the efficacy and safety data from two phase 3 clinical trials...These programs are independent of the ACG 2026 Annual Scientific Meeting and Postgraduate Course programs. No CME is provided for Exhibitor Product Theater presentations."

Pharmacotherapy of Irritable Bowel Syndrome with Constipation in Children: An Update on Clinical Progress and Successes. (PubMed, Drugs) - "Particular attention is given to newer agents approved for adults with irritable bowel syndrome with constipation, including secretagogues (linaclotide, plecanatide, and lubiprostone) and the retainagogue tenapanor, with a detailed discussion of their pharmacological properties and clinical trial data. While other novel agents have shown promise in adults, pediatric data remain limited or unavailable. Overall, although pharmacological treatment options for pediatric irritable bowel syndrome with constipation are expanding, high-quality, pediatric specific clinical trials are still needed to guide safe and effective management."

Journal • Review • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Pediatrics

Study to Assess Safety and Efficacy of Tenapanor for Treatment of IBS-C in Pediatric Patients 12 to Less Than 18 Years (clinicaltrials.gov) - P3 | N=180 | Completed | Sponsor: Ardelyx | Active, not recruiting ➔ Completed

Trial completion • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

Comparative and Subtractive Genomics Analysis of Multidrug-Resistant Klebsiella pneumoniae Strains for Novel Target Identification and Drug Repurposing Strategies. (PubMed, Int J Microbiol) - "Subsequent molecular dynamics simulations, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), hydrogen-bond occupancy, principal component analysis (PCA), and PCA-based free energy landscape (FEL) analyses, consistently identified tenapanor, micafungin, deferoxamine, and cobicistat as the most stable protein-ligand complexes, with tenapanor exhibiting the most favorable overall structural and thermodynamic stability profile. These findings identify accD as a promising therapeutic target in MDR K. pneumoniae and suggest several FDA-approved compounds as potential candidates for drug repurposing. Although experimental validation is needed to confirm their biological activity and therapeutic potential, this study demonstrates the potential of integrating comparative genomics with molecular dynamics analyses to support antimicrobial target identification and drug repurposing against MDR bacterial pathogens."

Journal • Infectious Disease • Pneumonia

Phosphate storm in chronic kidney disease-mineral and bone disorder: practical clinical strategies for vascular calcification control. (PubMed, Nephron) - "Our evaluation specifically focuses on three central aspects: dysregulated phosphate metabolism in VC progression, the clinical and physiological constraints of conventional phosphate binders, and novel interventions such as Tenapanor, vitamin K₂, and magnesium supplementation...In conclusion, while phosphate-centric management fails to halt VC, multitargeted strategies-integrating controlled phosphate absorption, anti-calcification agents, and personalized monitoring-show strong potential to improve CKD-MBD outcomes. This review proposes paradigm-shifting strategies to bridge the gap between biochemical control and actual prevention of VC."

Journal • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Orthopedics • Renal Disease • FGF23

Patients' Real-World Experiences With Pharmacologic Therapies for Irritable Bowel Syndrome With Constipation: A Mixed-Methods Analysis and Classification of Social Media and E-Forum Posts. (PubMed, Neurogastroenterol Motil) - "Social media provides unique insights into IBS-C patients' real-world experiences with FDA-approved therapies. Findings highlight variability in efficacy, biopsychosocial impacts, and adherence challenges, underscoring the need for shared decision making and proactive management of barriers to optimize outcomes."

Journal • Real-world evidence • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Mood Disorders • Psychiatry

Calcified amorphous tumor in a patient receiving peritoneal dialysis with severe, treatment-refractory hyperphosphatemia. (PubMed, Perit Dial Int) - "Phosphate control was limited despite having trialed sevelamer and calcium acetate and intolerance to tenapanor due to gastrointestinal adverse effects...Surgical excision remains the treatment of choice, with recurrence reported rarely. Given the propensity for calcium-phosphate deposition in patients with chronic hyperphosphatemia, strict phosphate control may reduce the risk of CAT development in patients with end-stage renal disease, though further studies are needed to clarify preventive strategies."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Oncology • Pain • Renal Disease • Solid Tumor • Type 2 Diabetes Mellitus

Patient characteristics associated with the need for high doses of tenapanor hydrochloride in dialysis patients with hyperphosphatemia: A pooled analysis of three clinical trials. (PubMed, PLoS One) - P3 | "The original clinical trials were registered at ClinicalTrials.gov under the identifiers NCT04767581, NCT04766398, and NCT04766385."

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

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

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

Real-World Efficacy and Safety of Tenapanor Plus Phosphate Binders in Hemodialysis Patients With Hyperphosphatemia (clinicaltrials.gov) - P=N/A | N=200 | Not yet recruiting | Sponsor: Peking University People's Hospital

New trial • Real-world evidence • Metabolic Disorders • Nephrology • Renal Disease

4-Week, Multi-center Dose-Ranging Study for the IBS-C in Pts. 6 to <12 Yrs (clinicaltrials.gov) - P2 | N=72 | Completed | Sponsor: Ardelyx | Active, not recruiting ➔ Completed

Trial completion • Constipation • Gastroenterology • Gastrointestinal Disorder

G protein‑coupled receptor kinase 4 governs early kidney development via STAT3 and Nhe3a. (PubMed, Int J Mol Med) - "The administration of the NHE3 inhibitor, tenapanor, restored normal kidney development and function. Of note, during embryogenesis, this modulation of Nhe3a is not connected to dopaminergic receptor signaling or to a possible nuclear function of GRK4. Instead, the present study identified elevated Stat3 activity as the underlying cause leading to increased Nhe3a transcription and subsequently, to defects in kidney development."

Journal • CNS Disorders • Nephrology • Renal Disease • Ventriculomegaly • STAT3

Pharmacological Management of Secondary Hyperparathyroidism in Dialysis Patients: A Narrative Review of Calcimimetics, Vitamin D Analogs, and Phosphate Binders. (PubMed, Cureus) - "Calcimimetics, particularly cinacalcet, reduce parathyroid hormone (PTH) by approximately 43% in hemodialysis patients without raising serum calcium, though hypocalcemia and gastrointestinal adverse effects limit tolerability. Intravenous etelcalcetide offers superior PTH suppression with improved gastrointestinal tolerability and eliminates oral adherence challenges through supervised dialysis-circuit administration...Novel agents including tenapanor offer complementary phosphate-lowering mechanisms with substantially reduced pill burden...A critical evidence gap exists in the GCC region, where diabetic nephropathy dominance, endemic vitamin D deficiency, and lower calcimimetic utilization may limit generalizability of existing trial data. Locally conducted research is urgently needed."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetic Nephropathy • Endocrine Disorders • Metabolic Disorders • Nephrology • Secondary Hyperparathyroidism

Renoprotective effects of gut NHE3 inhibitor tenapanor in a rat model of unilateral renal ischemia-reperfusion injury with contralateral nephrectomy. (PubMed, Biochem Biophys Rep) - "Here, we show that oral administration of tenapanor suppresses renal calcium phosphate deposition after I/R, mitigates AKI progression, and reduces subsequent renal fibrosis in rats. These findings suggest that tenapanor mitigates renal I/R injury and may represent a potential pre-transplant strategy to improve long-term graft outcomes."

Journal • Preclinical • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Metabolic Disorders • Nephrology • Renal Disease • Reperfusion Injury • Transplantation

Correction to Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). (PubMed, Am J Gastroenterol) - No abstract available

Journal • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder

Clinical Changes After Tenapanor Initiation in Maintenance Hemodialysis Patients: A Two-Center Retrospective Observational Study. (PubMed, Blood Purif) - "It was also linked with a reduction of IDWG modestly, but significantly, without adverse changes in key laboratory parameters. The correlation between the reduction of IDWG and that of serum phosphate might reflect a direct link between sodium/water and phosphate absorption."

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

Tenapanor reduces phosphate binder pill burden among hemodialysis patients in a post hoc phase 3 analysis. (PubMed, Sci Rep) - P3 | "Factors affecting the tenapanor dose at Week 50 were sex (P = 0.029), age (< 65 vs. ≥ 65 years; P = 0.008), normalized protein catabolic rate (< 0.80 vs. ≥ 1.00; P = 0.019), presence of diabetic nephropathy (P = 0.038), constipation (P = 0.015), and the occurrence of diarrhea as an adverse event (P = 0.009). Tenapanor consistently reduced the daily PB pill count and equivalent dose of PBs from baseline to Week 50 across all patient background factors evaluated (all P < 0.001 vs. baseline), thus demonstrating the clinical benefit of tenapanor regardless of patient background characteristics.Clinical Trial Registration ClinicalTrials.Gov (NCT04771780)."

Journal • P3 data • Retrospective data • Constipation • Diabetic Nephropathy • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease

Constipation with bloating: a clinical approach to evaluation and management. (PubMed, Ann Med) - "Management approaches discussed include dietary modification, biofeedback, and pharmacologic therapy, including over-the-counter treatments, plecanatide, linaclotide, lubiprostone, tenapanor, neuromodulators, and antibiotics. There is a need for additional research to further understand the physiology of bloating. In an era when personalized medicine is becoming increasingly emphasized, understanding the pathophysiology of bloating for an individual patient, be it alongside constipation or other GI and non-GI symptoms, will be paramount to improve treatment outcomes."

Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder

Tenapanor-Associated Bowel Effects in Hemodialysis: Persistence Barriers and Practical Continuation Strategies. (PubMed, Hemodial Int) - "Tenapanor-associated bowel effects are a central implementation barrier rather than a secondary tolerability issue. Persistence may be improved by matching treatment to baseline bowel phenotype and using a tolerability-first, safety-conscious continuation framework. Prospective studies should define predictors of persistence and validate supportive strategies."

Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Mood Disorders • Nephrology • Psychiatry • Renal Disease

How are developments in the treatment armamentarium of hyperphosphatemia addressing the current therapeutic challenges? (PubMed, Expert Opin Pharmacother) - No abstract available

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

4-Week, Multi-center Dose-Ranging Study for the IBS-C in Pts. 6 to <12 Yrs (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: Ardelyx | Recruiting ➔ Active, not recruiting

Enrollment closed • Constipation • Gastroenterology • Gastrointestinal Disorder