irbesartan / Generic mfg. - LARVOL DELTA

Decoding the Neuroprotective Intervention of Angiotensin Receptor Blockers: A Multimodal Approach Using In Silico Network Pharmacology, Molecular Modeling, and In Vivo Validation of Key Markers. (PubMed, ACS Chem Neurosci) - "Building on these findings, this study sought to compare the activity of azilsartan with other commonly used ARBs, including telmisartan, olmesartan, valsartan, eprosartan, irbesartan, and candesartan, using an integrative network pharmacology approach. To experimentally validate these predictions, in vivo studies were conducted in a scopolamine-induced memory-impaired model, which demonstrated significant restoration of the levels of AKT1 and PIK3CA. These findings clearly demonstrate the PI3K/AKT modulating effects of azilsartan, reinforcing its repurposing potential in dementia and related disorders, thereby expanding novel therapeutic opportunities within this drug class."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • AKT1 • PIK3CA • PIK3CB

A systematic review of commencing full dose antihypertensives in newly diagnosed hypertension. (PubMed, Blood Press) - "The review assessed commonly used antihypertensive drugs (perindopril 8 mg, ramipril 10 mg, amlodipine 10 mg, losartan 100 mg, irbesartan 300 mg, candesartan 16 mg and candesartan 32 mg) compared to low starting doses or placebo RCTs. The review indicates that initiating full dose antihypertensives for essential hypertension may be beneficial and safe. The available data are limited and further RCTs are required to assess this in specific patient groups to assess safety and efficacy."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Hypertension • Nephrology • Renal Disease

Pharmacogenomics-Guided Precision Therapy for Chronic Kidney Disease with Resistant Hypertension: A Prospective Cohort Study. (PubMed, Kidney Blood Press Res) - "PGx-guided precision therapy facilitates rapid BP control, reduces polypharmacy and adverse events, and delays kidney function decline in CKD patients with RH. This study, the first PGx clinical trial targeting a multi-ethnic population in Northwest China, offers valuable insights into personalized treatment approaches for CKD with RH in East Asia."

Biomarker • Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Post-translational switch of DHCR24 acetylation sustains sterol synthesis and promotes HCC via the 7-ketocholesterol/p62 axis. (PubMed, Cell Rep) - "Pharmacologic inhibition of DHCR24 expression and acetylation with the US Food and Drug Administration (FDA)-approved drug irbesartan suppresses cell proliferation and reduces tumor burden in xenograft and carcinogen-induced mouse models. Reduced p62 expression parallels the antitumor effects. These findings define DHCR24 acetylation as a metabolic switch linking sterol synthesis to oncogenesis and highlight the DHCR24-7-ketocholesterol-p62 axis as a therapeutic target for HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Primary aldosteronism: pharmacotherapy vs surgery vs embolization efficacy - systematic review and network meta-analysis of studies predominantly conducted in China. (PubMed, Front Endocrinol (Lausanne)) - "Among pharmacological treatments, mineralocorticoid receptor antagonists and irbesartan (MRAs+IRB) had the greatest antihypertensive effect (SBP: WMD = -18.90, 95% Crl -29.20 to -8.55; DBP: WMD = -22.14, 95% Crl -31.81 to -12.50)...This study showed TADR + RND and MRAs + IRB had best efficacy in surgical and pharmacological treatments, respectively, but 76% of the included studies were conducted in China, which may affect the generalizability of the findings. Therefore, the results need further validation."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Endocrine Disorders • Hypertension

Angiotensin II Activates Yes-Associated Protein (YAP) in Fibroblast Promoting Deep Fascia Remodeling. (PubMed, Int J Mol Sci) - "This gene expression was decreased by pretreatment with the AT1R antagonist irbesartan or the YAP inhibitor verteporfin. These findings show that Ang II acts as both a biochemical and biomechanical signal in the deep fascia, activating YAP signaling and promoting fibrotic remodeling. Our results uncover a new Ang II-YAP pathway in fascial fibroblasts, offering potential targets for therapy in fibrosis and related conditions involving the deep fascia."

Journal • Fibrosis • Immunology • Pain • COL1A1 • COL3A1

Adherence, Switches, and Drug Spending After Angiotensin Receptor Blocker Recalls and Shortages. (PubMed, JAMA Health Forum) - "From 2018 to 2019, hundreds of valsartan, losartan, and irbesartan products were recalled due to ingredient impurities. This cohort study shows that access to alternatives may have mitigated gaps in treatment during the 2018 to 2019 ARB recalls and drug shortages. Potential disparate impacts among certain subgroups highlight the need for policies to mitigate financial and other systematic access barriers to receiving health care during drug shortages."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hypertension • Nephrology • Renal Disease

Matching-adjusted indirect comparison of kidney function in patients with immunoglobulin A nephropathy treated with nefecon or sparsentan. (PubMed, J Comp Eff Res) - P3 | "Aim: We compared the effects of nefecon, an oral targeted-release budesonide formulation, and sparsentan, an oral, dual endothelin-angiotensin receptor antagonist, on estimated glomerular filtration rate (eGFR) in patients with immunoglobulin A nephropathy, a leading cause of chronic kidney disease. Materials & We conducted an anchored matching-adjusted indirect comparison (MAIC) using patient-level data from NefIgArd (NCT03643965; n = 364), a randomized (1:1) trial of nefecon plus optimized renin-angiotensin system inhibitor (RASi) therapy versus placebo plus RASi; and aggregate data from PROTECT (NCT03762850; n = 404), a randomized (1:1) trial of sparsentan versus irbesartan, an angiotensin receptor blocker...Sensitivity analysis results were consistent with the main findings. In patients with immunoglobulin A nephropathy, nefecon plus optimized RASi may preserve kidney function to a greater extent than sparsentan."

Journal • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

A Case Report of Fabry Disease Combined with IgAN (KIDNEY WEEK 2025) - "After six months of ERT(enzyme replacement therapy), irbesartan and hydroxychloroquine sulfate treatment, the urine protein of the patient turned negative. It is vital to improve the detection rate of the disease by combining family history, clinical manifestations, α-Gal A activity, and genetic testing. Kidney biopsy specimens in the patient."

Case report • Clinical • Fabry Disease • Genetic Disorders • Glomerulonephritis • IgA Nephropathy • Renal Disease

IgAN with Orthostatic Proteinuria: A Case Report (KIDNEY WEEK 2025) - "Over this period, due to poorly controlled proteinuria, he had been given various treatment regimens on top of RASi support therapy, including steroids, Tacrolimus, leflunomide, hydroxychloroquine, mycophenolate mofetil, ambrisentan, and Tripterygium wilfordii polyglycoside, but his spot urine protein levels remained unsatisfactory...We thus considered that the patient had IgAN coexisting with orthostatic proteinuria and withdrew immunosuppressive medications, retaining only irbesartan at 150 mg/day...This case underscores the importance of considering this diagnosis in adult IgAN patients with discordant findings or poor response to treatment. Routine use of split urine collections, especially in patients with variable home test results, can help avoid misdiagnosis and overtreatment."

Case report • Clinical • Glomerulonephritis • IgA Nephropathy • Ophthalmology • Renal Disease

Rituximab (RTX): Not Only Effective in Anti-Phospholipase A2 Receptor (PLA2R)-Associated Membranous Nephropathy (MN) (KIDNEY WEEK 2025) - "Case Description 66 years old man with history of T-cell lymphoblastic lymphoma status post allogenic HSCT 2 years before presentation, complicated by chronic GVHD with skin and liver involvement, chronically on ruxolitinib and briefly on belumosudil, presented with acute onset lower extremity edema, proteinuria 7600 mg in 24 hours, serum albumin 2.1 g/dL, serum creatinine 1.3 mg/dL (base 1.1)...Irbesartan started, apixaban for DVT prophylaxis, atorvastatin and evolocumab for dyslipidemia...Clinically doing excellent in complete remission, remains on irbesartan, dapagliflozin, atorvastatin, and evolocumab. Discussion Treatment of MN post allogenic HSCT is based on case report and case series, and different agents have been used including calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, and more recently rituximab...The lack of serological markers (i.e. antiPLA2R antibody) made the decision to continue with RTX and not changing to a different agent..."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Dyslipidemia • Glomerulonephritis • Graft versus Host Disease • Hematological Malignancies • Immunology • Lymphoma • Metabolic Disorders • Renal Disease

Primary Hyperaldosteronism Presenting Clinically as Classic Pheochromocytoma (KIDNEY WEEK 2025) - "Therapy at the time included irbesartan 300mg daily, nebivolol 20mg daily, amlodipine 10mg daily and hydralazine 10mg three times daily. Symptoms of profuse sweating, palpitations and impending sense of doom are often associated with pheochromocytomas which can also result in hypertension. This case demonstrates how variability can exist in symptomatic burden."

Clinical • Cardiovascular • Endocrine Disorders • Hypertension • Solid Tumor

Patients (Pts) with FSGS Reach Proteinuria <0.7 g/g More Often with Sparsentan (SPAR) vs. Irbesartan (IRB) in DUPLEX: Implications for Kidney Failure (KF) Risk (KIDNEY WEEK 2025) - P3 | "Conclusion In DUPLEX, pts with FSGS achieved UPCR <0.7 g/g earlier and more often with SPAR vs IRB. Together, clinical trial and real-world data indicate that reaching UPCR <0.7 g/g is associated with clinically meaningful reductions in KF risk both in the near- and long-term, supporting the long-term benefit of SPAR’s anti-proteinuric effect."

Clinical • Late-breaking abstract • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease

Real-World Data on Low Proteinuria with Sparsentan (SPAR) in Patients (Pts) with IgAN: A Case Series (KIDNEY WEEK 2025) - "In PROTECT, SPAR was well tolerated (95% of pts received the target dose [400 mg/d]) and lowered proteinuria, leading to complete remission (CR) of proteinuria more often vs maximum labeled dose irbesartan. In 3 pts with intolerance to the 400-mg/d dose, dose modification (200 mg/d or alternating 200 mg/400 mg every other day) was well tolerated, with effective proteinuria control (UPCR <0.5 g/g). Discussion This case series supports the benefit of SPAR, alone or in combination with other txs, on achieving clinically meaningful low proteinuria thresholds, including CR, with real-world use in pts with IgAN."

Clinical • Real-world • Real-world evidence • Glomerulonephritis • IgA Nephropathy • Renal Disease

Nefecon (Targeted-Release Formulation of Budesonide) for IgAN: Two Case Reports (KIDNEY WEEK 2025) - "Initial treatment included methylprednisolone, prednisone, and telitacicept...The patient received irbesartan and entecavir...Discussion These cases highlight the potential of Nefecon as an effective therapy for IgAN, even in patients with advanced histologic damage and impaired renal function. The observed clinical benefits, including reduction in proteinuria and stabilization of renal function, supports its therapeutic value in real-world settings."

Case report • Clinical • Glomerulonephritis • Hepatitis B • Hepatology • IgA Nephropathy • Infectious Disease • Inflammation • Lupus Nephritis • Nephrology • Renal Disease

Impact of Histology on Efficacy of Sparsentan Therapy in IgAN: Central Biopsy Review of Patients in the PROTECT Trial (KIDNEY WEEK 2025) - "Background In PROTECT, sparsentan (SPAR), a non-immunosuppressive, dual endothelin angiotensin receptor antagonist, resulted in significant reduction in proteinuria and preservation of kidney function when compared to irbesartan (IRB) in adults with IgA nephropathy. The % tubular atrophy/interstitial fibrosis and % of glomeruli showing segmental sclerosis showed a significant negative correlation with BL eGFR whilst % of glomeruli showing endocapillary hypercellularity positively correlated with BL eGFR. The reduction in proteinuria at 36 weeks in pts treated with SPAR (n=47) was consistent across MEST-C scores or continuous histological data; pts showed treatment benefit in all groups (Fig 1) Conclusion Whilst histological features are associated with baseline eGFR and proteinuria, the therapeutic efficacy of SPAR is independent of biopsy findings, including the Oxford Classification MEST-C scores."

Biopsy • Clinical • Review • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Renal Disease

Estimating the Benefits of Proteinuria Reduction on Kidney Failure Risk in the DUPLEX Study Using an Aligned FSGS Cohort from the UK RaDaR Registry (KIDNEY WEEK 2025) - "This work quantifies the likely benefits of proteinuria reduction observed in the DUPLEX study of sparsentan (SPAR) on risk of KF events, by extracting a cohort from RaDaR aligned to the DUPLEX population...Applied to DUPLEX, where a 26% relative UPCR reduction was observed, the model predicts a HR of 0.77 (95% CI 0.70-0.85) (SPAR vs irbesartan) for KF risk. Conclusion Analysis of the DUPLEX-aligned RaDaR cohort is consistent with PARASOL findings and predicts a significant and clinically meaningful benefit in 84-month kidney survival for the relative reductions in UPCR observed with SPAR in DUPLEX. These results are corroborated by lower KF event rates seen in the SPAR arm of DUPLEX."

Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease

Sparsentan (SPAR) vs. Irbesartan (IRB) in Pediatric Patients with FSGS in the Phase 3 DUPLEX Trial (KIDNEY WEEK 2025) - P3 | "SPAR had a safety profile that was comparable to IRB; no pts in the SPAR arm and 2 pts in the IRB arm discontinued treatment due to adverse events ( Table ). Conclusion Consistent with findings in the overall DUPLEX population, SPAR was well tolerated and led to rapid and sustained proteinuria reductions vs maximum labeled dose IRB in pediatric pts with FSGS."

Clinical • P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Pediatrics • Renal Disease

Sparsentan Slows the Loss of Kidney Function in Patients with IgAN: Post Hoc Analyses of the Phase 3 PROTECT Study (KIDNEY WEEK 2025) - "This post -hoc analysis compares the efficacy of SPAR vs. irbesartan (IRB) in preventing the progression to chronic kidney disease (CKD) stages 4 or 5 and was conducted as part of the HTA process in Germany. Statistically significantly fewer patients progress to CKD stages 4 or 5 under SPAR, and the time to reach CKD stages 4 or 5 is prolonged —an effect outcome that was accepted as patient-relevant in the German HTA process and led to an evidence-based additional benefit. Table 1: Patients with CKD stages 4 or 5 until Week 110"

Clinical • P3 data • Retrospective data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Sparsentan (SPAR) in Participants with FSGS and Collagen Type IV Alpha 3-5 Chain (COL4A3-5) Variants (KIDNEY WEEK 2025) - P3 | "Background In DUPLEX, SPAR led to sustained proteinuria reductions vs irbesartan (IRB) in participants with FSGS that were consistent in participants with podocyte gene mutations. Conclusion Consistent with the overall DUPLEX population, participants with FSGS and COL4A3-5 variants had more pronounced and durable proteinuria reductions with SPAR vs IRB. While long-term follow-up and larger sample sizes are needed to further assess SPAR’s impact in this population, findings suggest SPAR could have a meaningful impact in participants with COL4A3-5 variants, a group for which there are no approved therapies."

Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease • Tumstatin

PROTECT Post Hoc Analysis: Efficacy of Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients (Pts) with IgAN ≤12 mo vs. >12 mo from Kidney Biopsy (KIDNEY WEEK 2025) - "Conclusion SPAR showed better efficacy vs maximum labeled dose IRB regardless of time from biopsy, with greater kidney preservation with shorter time from biopsy. These results emphasize the value of early SPAR treatment."

Biopsy • Clinical • Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Adult-Onset NPHS1 Nephrotic Syndrome: Two Cases Highlighting Diagnostic and Therapeutic Gaps (KIDNEY WEEK 2025) - "Irbesartan maintained proteinuria at 0.4–0.7 g/day, but was discontinued during pregnancy in 2021, causing a surge to 10 g/day with hypertension, prompting preterm delivery...Sparsentan, a potentially effective treatment for FSGS, was denied for off-label use by insurance...Treatment with lisinopril (5 mg/day), tacrolimus (2.5 mg BID), rosuvastatin (10 mg daily), and a low-sodium diet raised albumin to 2.7 g/dL and reduced proteinuria to 1.5 g/day by 2025...The lack of clear treatment strategies for NPHS1 -related disease adds to patient burden, underscoring the need for evidence-based care. These cases show the importance of expanding access to genetic testing, developing targeted therapies, and establishing treatment guidelines to bridge the gap between genetic diagnosis and therapeutic uncertainty."

Clinical • Cardiovascular • Dyslipidemia • Fatigue • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hypertension • Metabolic Disorders • Mood Disorders • Nephrology • Psychiatry • Renal Disease • NPHS1

Effects of Neprilysin Inhibition on Urine Tubular Biomarkers in CKD: Findings from the UK HARP III Trial (KIDNEY WEEK 2025) - "Methods The effects of sacubitril/valsartan 200mg twice daily vs irbesartan 300mg once daily on creatinine-indexed urine biomarkers were assessed using spot samples in 411 participants from UK HARP III at baseline, 3 months, and 6 months. Its effect on NGAL suggests neprilysin inhibition may have distal tubular effects in CKD. Values show study average biomarker levels."

Biomarker • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Nephrology • Renal Disease • CCL2 • CHI3L1 • DKK3 • EGF • IL18 • KIM1 • LCN2

Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis. (PubMed, Open Med (Wars)) - "Dobutamine stress echocardiography (DSE) and resting echocardiography were performed on 73 patients with LG-AS. A projected aortic valve area (AVAproj) ≤ 1 cm2 or indexed AVAIproj < 0.60 cm2/m2 was defined as true-severe AS...Serum micronutrients had good predictive value for true-severe AS and AVAI, and mean PG improved the predictive value of serum micronutrients. Serum micronutrients have diagnostic values for true-severe AS in patients with LG-AS."

Journal • Cardiovascular

Surrogate Endpoints in German Health Technology Assessment: Post Hoc Analyses of the Phase III PROTECT Study Highlight the Efficacy of Sparsentan in Slowing Down the Loss of Kidney Function in IgAN Patients (ISPOR-EU 2025) - "A post hoc analyses that led to the recognition of an evidence based "additional benefit" in Germany's HTA. The RCT PROTECT examined the efficacy and safety of sparsentan (n=202) vs. maximum labeled dose Irbesartan (n=202) in adult patients with biopsy-proven IgAN over 110 weeks. Sparsentan significantly slowed renal function decline, reducing progression to CKD stages 4 or 5. These findings underscore the overall RCT and the importance of clinically relevant endpoints. The German HTA process should consider surrogate endpoints for CKD as patient relevant as they reflect critical diagnostic and prognostic indicators to derive an additional benefit."

Clinical • P3 data • Retrospective data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease