Vafseo (vadadustat) / Akebia Therap, Tanabe Pharma, CSL Behring, Medice - LARVOL DELTA

To Evaluate the Efficacy of Three Times Weekly (TIW) Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center Hemodialysis (clinicaltrials.gov) - P3 | N=353 | Completed | Sponsor: Akebia Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Vadadustat for the Treatment of Nonintubated Acute Respiratory Distress Syndrome Due to Pathogen-Associated Lung Injury (clinicaltrials.gov) - P2/3 | N=1100 | Recruiting | Sponsor: Paul Potnuru | Trial completion date: Jul 2026 ➔ May 2031 | Trial primary completion date: Jul 2026 ➔ May 2031

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Impact of SLCO1B1 Gene Polymorphisms on Vadadustat Pharmacokinetics. (PubMed, Eur J Drug Metab Pharmacokinet) - "SLCO1B1*15 significantly influenced vadadustat concentration, and CP-I was associated with vadadustat C12/D, suggesting an association with OATP1B1-related transporter function. These findings provide insights into variability in vadadustat PK and support the larger studies to clarify the clinical utility of therapeutic drug monitoring strategies that incorporate pharmacogenomic and biomarker information. Video abstract available in online supplementary file. Supplementary file2 (MP4 35720 KB)."

Journal • PK/PD data • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • SLCO1B1

Supramolecular host-guest interactions of TRYVIO and VAFSEO with a benzotriazole nanocapsule: A density functional theory study. (PubMed, J Mol Graph Model) - "The higher value of dipole moments of the complexes indicated their high polarity and improved solubility in the polar solvents. Overall, the findings establish the benzotriazole supramolecular nanocapsule as an effective therapeutic carrier of CKD therapeutics."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

VOTE: Safety and Efficacy of a Phased Transition From Epogen to Three Times Weekly Oral Vadadustat for the Treatment of Anemia in Subjects Receiving In-Center Hemodialysis (clinicaltrials.gov) - P3 | N=100 | Not yet recruiting | Sponsor: Geoff Block

New P3 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Vadadustat TIW vs MPG-EPO by Baseline MPG-EPO Dose in Patients with Anemia Due to DD-CKD (NKF-SCM 2026) - P3 | "CONCLUSION Patients on high MPG-EPO doses at baseline had a greater initial Hb decline after switching to VADA than patients on low MPG-EPO. Starting VADA at 900 mg TIW may be preferred for patients switching from MPG-EPO to avoid an initial decline in Hb."

Clinical • Late-breaking abstract • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Transitioning from QD to TIW Vadadustat: When and What Dose? (NKF-SCM 2026) - "These changes are not expected to be clinically significant. CONCLUSION Transitioning VADA from QD to TIW dosing at 2X the QD dose can be initiated as early as 2 weeks after treatment start, maintaining Hb within target range in most patients without meaningful alteration in VADA exposure"

Chronic Kidney Disease • Hematological Disorders

A Near-Infrared Photoactivatable, Brain-Penetrant Prodrug of the Prolyl Hydroxylase Inhibitor Vadadustat for Neuroprotection in Ischemic Stroke. (PubMed, J Med Chem) - "Moreover, in a mouse model of cerebral ischemia-reperfusion (I/R), prodrug 11 reduced infarct volume and brain edema, and promoted neurological recovery. These findings highlight a photoactivatable, brain-penetrant prodrug strategy for spatiotemporally controlled neuroprotection."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Reperfusion Injury

Effects of Vadadustat on Anemia, Quality of Life, and Inflammation in Dialysis Patients (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Mackay Memorial Hospital

HEOR • New P4 trial • Anemia • Hematological Disorders • Inflammation

REAL-WORLD ANEMIA MANAGEMENT BEFORE HEMODIALYSIS INITIATION IN JAPAN: A RETROSPECTIVE MULTICENTER COHORT STUDY (ISN-WCN 2026) - "ESA was used in 60%, HIF-PHIs in 30%, and no erythropoietic agents in 10%, with the following distribution: darbepoetin alfa 34%, epoetin beta pegol 26%, daprodustat 25%, roxadustat 3%, vadadustat 1%, and enarodustat 1%. In a multivariate logistic regression model adjusted for sex, age, and transferrin saturation, lower Hb 6 months prior was independently associated with Hb < 9 g/dL at HD initiation (p < 0.001), without significant differences between ESA and HIF-PHI groups.Conclusion Despite contemporary anemia therapy, 60% of patients presented with Hb < 10 g/dL and one-third with Hb < 9 g/dL at HD initiation. Lower baseline Hb strongly predicted suboptimal Hb control, suggesting that earlier dose adjustment and closer monitoring are warranted during progression to end-stage kidney disease."

Real-world • Real-world evidence • Retrospective data • Acute Kidney Injury • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Glomerulonephritis • Heart Failure • Hematological Disorders • Lupus Nephritis • Nephrology • Renal Disease • STAT3

EFFICACY OF HIF-PHD INHIBITORS FOR RENAL ANEMIA IN PERITONEAL DIALYSIS PATIENTS: A SINGLE-CENTER RETROSPECTIVE STUDY (ISN-WCN 2026) - "Among 49 PD patients treated with HIF-PHD inhibitors daprodustat or vadadustat, 15 patients met the inclusion criteria:(1) switched from ESA therapy (patients with prior HIF-PHD inhibitor or without prior ESA use were excluded) and (2) baseline Hb < 11 g/dL. The improvement was particularly evident among those with baseline Hb < 10 g/dL. These findings support the clinical utility of HIF-PHD inhibitors as an effective alternative to ESA therapy in PD populations though larger prospective studies are warranted."

Retrospective data • Anemia • Hematological Disorders

Comparing Vadadustat and Darbepoetin in Maintenance Dialysis with CKD-Related Anemia: A Win Statistics Analysis. (PubMed, J Am Soc Nephrol) - No abstract available

Journal • Anemia • Hematological Disorders

VOICE: Vafseo Outcomes In-Center Experience (clinicaltrials.gov) - P3 | N=2200 | Active, not recruiting | Sponsor: USRC Kidney Research | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

To Evaluate the Efficacy of Three Times Weekly (TIW) Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center Hemodialysis (clinicaltrials.gov) - P3 | N=353 | Active, not recruiting | Sponsor: Akebia Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications. (PubMed, Curr Ther Res Clin Exp) - "Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters...Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Mechanistic DDI..."

Clinical data • FDA event • Journal • NDA • PK/PD data • Review • CYP1A2 • CYP2C9

Barriers and Facilitators to Vadadustat Use for Managing Anemia in Adult Patients Undergoing Dialysis: A Qualitative Evidence Synthesis. (PubMed, Cureus) - "Based on these findings, we propose a synthesis-derived multidisciplinary implementation framework built on six core principles: evidence-based patient selection, risk stratification and monitoring, shared decision-making, gradual transition strategies, interdisciplinary team engagement, and outcomes-based evaluation. Understanding these implementation determinants is crucial for optimizing anemia management in the dialysis population, ensuring that appropriate patient subgroups can benefit from vadadustat administration while balancing safety and cost-effectiveness."

Journal • Review • Anemia • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Hematological Disorders • Nephrology • Renal Disease

Efficacy and safety of prolyl hydroxylase inhibitors for anemia in chronic kidney disease: a network meta-analysis. (PubMed, Ren Fail) - "Roxadustat improved serum iron in D-CKD (MD = 6.19 μg/dL, 95% CI: 2.81-9.58), and vadadustat and roxadustat reduced hepcidin in ND-CKD. Regarding safety, ESA had the lowest AE risk in ND-CKD (OR = 0.85, 95% CI: 0.74-0.98), while roxadustat ranked lowest (SUCRA = 18.4%). Roxadustat demonstrated the strongest efficacy in hemoglobin improvement but higher AE incidence in ND-CKD, whereas ESA and daprodustat showed safety and iron metabolism benefits, supporting individualized therapy for renal anemia.Registration number: PROSPERO (CRD420251066181)."

Clinical • Journal • Retrospective data • Review • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Safety and Efficacy of Vadadustat Versus Darbepoetin Alfa for Chronic Kidney Disease-Related Anemia in Patients Receiving Dialysis by Baseline Erythropoiesis-Stimulating Agent Dose. (PubMed, Hemodial Int) - "Comparing safety and efficacy by baseline ESA dose among patients with CKD on maintenance dialysis, vadadustat was noninferior to darbepoetin alfa for all ESA dose subgroups, including patients with high baseline ESA requirements."

Journal • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Discovery of 3-(Arylamido)pyrazolopyridine HIF-2α Agonists and a Codrug Strategy with Prolyl Hydroxylase Inhibition for Synergistic Treatment of Renal Anemia. (PubMed, J Med Chem) - "In cellular assays, 48 synergistically enhanced HIF-2α-dependent EPO gene expression when combined with the clinically approved prolyl hydroxylase domain (PHD) inhibitor Vadadustat...Notably, codrug 50 induced superior upregulation of EPO levels in vivo compared to coadministration of the two individual agents. Together, these findings demonstrate the first rationally designed codrug integrating an HIF-2α agonist and a PHD inhibitor, highlighting a new direction for the development of renal anemia therapies."

Journal • Anemia • Hematological Disorders • EPAS1 • EPO

Treatment of an Anemic Patient with CKD with Oral Vadadustat (KIDNEY WEEK 2025) - "Patient's extra-renal systemic lupus has stablized with use of hydroxychloroquine and low dose mycophenolate...In January of 2025 she was swithced from epogen to vadadustat 300 mg oral daily...This case demonstrates that some patients may respond quicker, reducing requirement of frequent high dose of synthetic erythropoietin. Anemia Management Report"

Clinical • Anemia • Chronic Kidney Disease • Glomerulonephritis • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus • STAT3

Model-Based Vadadustat Starting Dose Recommendations in Patients with Dialysis-Dependent CKD (KIDNEY WEEK 2025) - "Simulations were performed in virtual dialysis-dependent patients with bl characteristics of interest (ESA experienced/naïve, bl Hb ≥ or <10 g/dL, and bl standardized ESA dose ≥ or < 90 IU/kg/wk Epogen equivalents). Patients with higher bl Hb or lower prior ESA dose were more likely to achieve satisfactory Hb response at a lower VADA starting dose. Conclusion A VADA starting dose of 450 mg QD or 900 mg TIW should ameliorate the transitory decline in Hb following a switch from ESA in most patients."

Clinical • Late-breaking abstract • Anemia • Chronic Kidney Disease • Hematological Disorders

Three Times Weekly In-Center Vadadustat vs. Standard of Care Erythropoiesis-Stimulating Agent (ESA) for Treatment of CKD-Related Anemia in Patients Undergoing Dialysis (VOCAL) (KIDNEY WEEK 2025) - P3 | "This study will provide additional data on the efficacy of TIW vadadustat compared to SOC ESA for the treatment of anemia in patients receiving TIW ICHD."

Clinical • Anemia • Chronic Kidney Disease • Hematological Disorders

Vadadustat Outcomes In-Center Experience (VOICE) Study: Pragmatic Randomized Controlled Trial to Test the Safety of Three Times Weekly Vadadustat (KIDNEY WEEK 2025) - P3 | "Methods This randomized controlled trial is testing whether TIW vadadustat is non-inferior to epoetin alfa on the primary hierarchical outcome of all-cause mortality and all-cause hospitalization analyzed using the win ratio ( NCT06520826) . Conclusion The VOICE trial design showcases a pragmatic approach to embed individual-level randomized clinical trials in routine dialysis care. The trial will generate critical data on the safety of a new anemia management strategy while leveraging a composite hierarchical outcome to optimize statistical efficiency and clinical relevance."

Clinical • Anemia • Hematological Disorders

Consistency of the Estimate of Responsiveness of Vadadustat vs. Darbepoetin (KIDNEY WEEK 2025) - "Conclusion Lower responsiveness variability in NDD and DD Vadadustat-treated patients suggests more precise Hb control, supporting the potential of a personalized dosing algorithm to improve anemia management. Normalized responsiveness histograms: Darbepoetin vs. Vadadustat in NDD and DD trials Table 1: Adjusted standard deviations of responsiveness"

Anemia • Hematological Disorders • Inflammation

Win-Odds Analysis of Deaths and Hospitalization in Patients Taking Vadadustat or Darbepoetin Alfa for CKD-Related Anemia Undergoing Dialysis (KIDNEY WEEK 2025) - "The win odds (95% CI) for VADA compared to DA was 0.93 (0.87–0.99; p=0.03). Conclusion In a post-hoc analysis, the composite of all-cause mortality and hospitalizations was statistically significantly lower for VADA compared to DA in a win-odds analysis among patients with DD- CKD."

Clinical • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Myocardial Infarction