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

Vadadustat U.S. Patient Data from Global Phase 3 Clinical Program Published in Journal of the American Society of Nephrology (Akebia Press Release) - P3 | N=369 | NCT02865850 | P3 | N=3,554 | NCT02892149 | P3 | N=1,751 | NCT02648347 | P3 | N=1,725 | NCT02680574 | Sponsor: Akebia Therapeutics | "Akebia Therapeutics, Inc...announced that the Journal of the American Society of Nephrology (JASN) has published pre-specified analyses for the U.S. and non-U.S. patient subgroups from the vadadustat global phase 3 clinical program, which included two trials in patients with dialysis-dependent chronic kidney disease (DD-CKD; INNO2VATE) and two trials in patients with non–dialysis-dependent CKD (NDD-CKD; PRO2TECT)...Data from the pre-specified analyses for the U.S. patient subgroup demonstrate that among patients with DD-CKD, safety and efficacy of vadadustat and darbepoetin alfa in the U.S. and outside the U.S. were similar. Among the U.S. patient subgroup with NDD-CKD, safety and efficacy outcomes were similar..."

P3 data • Chronic Kidney Disease

A Win-Ratio Analysis of the Cardiovascular Safety of Vadadustat in Patients With CKD-Related Anemia Undergoing Dialysis (ERA 2025) - "Vadadustat was noninferior to darbepoetin alfa in a win-ratio analysis of cardiovascular safety among patients with dialysis-dependent CKD in the global INNO 2VATE trials. Results from this win-ratio analysis were consistent with the results from the original time-to-first event analysis of the INNO 2VATE trials."

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

Vadadustat Combination with Ferric Citrate, Compared to Either Agent Alone, Protects Against Inflammation-Induced Anaemia and Anaemia-Induced by Chronic Kidney Disease (ERA 2025) - "Collectively, these data suggest vadadustat in combination with oral iron provides greater improvement in anaemia related parameters in models of inflammation-induced anaemia and CKD than when either agent is given alone."

Anemia • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease • CRP • FGF21 • HP • IL15 • IL6

Evolution Of Anemia Treatment With Hif-Ph Inhibitors In Europe (ERA 2025) - "The first hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, roxadustat, was approved in Europe in 2021, followed by vadadustat in 2023, marking the first new treatments for renal anemia since erythropoiesis- stimulating agents (ESAs) were introduced in 1988. The adoption of HIF-PH inhibitors for anemia treatment has been gradual, but significant opportunities exist for broader integration to enhance patient outcomes. These agents hold particular promise for treatment-naïve patients, ESA hypo-responders, and those with suboptimal responses to ESA therapy, offering a potential shift toward more effective and individualized care."

Anemia • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease

Therapeutic Hypoxia-inducible Factor 1α Stabilization Activates Antimicrobial Peptide Expression and Prevents Bacterial Pneumonia (ATS 2025) - "We found that treating lung epithelial surfaces by inhalation with the prolyl-hydroxylase domain (PHD) inhibitor vadadustat stabilizes HIF-1α, resulting in activation of HIF-1α-dependent signaling that protects against Pseudomonas pneumonia in mice...These data indicate that induction of antimicrobial HIF-1α signaling contributes to ODN inducible resistance. This finding offers insights for rational design of alternate strategies to protect against fatal lung infection in patients with impaired immunity."

Late-breaking abstract • Infectious Disease • Pneumonia • HIF1A

Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs) (clinicaltrials.gov) - P3 | N=319 | Completed | Sponsor: Akebia Therapeutics | Phase classification: P3b ➔ P3

Phase classification • Anemia • Hematological Disorders

HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses. (PubMed, Cancer Immunol Immunother) - "Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8 • HIF1A

Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States. (PubMed, J Am Soc Nephrol) - "In patients with DD-CKD, safety (vis-à-vis MACE) and efficacy (vis-à-vis change in hemoglobin) of vadadustat and darbepoetin alfa were similar when stratified by region (US versus non-US). In US patients with NDD-CKD, safety and efficacy of vadadustat and darbepoetin alfa were similar."

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

Vascular Access Thrombosis Events in Patients With Dialysis-Dependent CKD Treated With Vadadustat or Darbepoetin Alfa: The INNO2VATE Trial Program. (PubMed, Kidney Med) - P3 | "In this secondary analysis of the INNO2VATE program in patients with DD-CKD and CKD-related anemia receiving hemodialysis, first VAT rates were numerically higher among patients treated with vadadustat versus darbepoetin alfa but statistically not different. The rates of first and recurrent VAT events were similar between treatment groups."

Clinical • Journal • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Thrombosis

Clinical Pharmacokinetics and Pharmacodynamics of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor. (PubMed, Eur J Drug Metab Pharmacokinet) - "The rates and severity of adverse events with vadadustat and erythropoietin are similar. Given that vadadustat is taken orally and has a beneficial efficacy and safety profile, it represents a meaningful addition to the standard treatment for anemia associated with renal failure, working alongside erythropoietin."

Journal • PK/PD data • Review • Chronic Kidney Disease • Gastrointestinal Disorder • Hematological Disorders • Nephrology • Renal Disease

Derivatives of the Clinically Used HIF Prolyl Hydroxylase Inhibitor Desidustat Are Efficient Inhibitors of Human γ-Butyrobetaine Hydroxylase. (PubMed, J Med Chem) - "We report that the clinically used hypoxia-inducible factor-α prolyl residue hydroxylase (PHD) inhibitors Desidustat, Enarodustat, and Vadadustat efficiently inhibit isolated recombinant BBOX, suggesting that BBOX inhibition by clinically used PHD inhibitors should be considered as a possible off-target effect. Structure-activity relationship studies on the Desidustat scaffold enabled development of potent BBOX inhibitors that manifest high levels of selectivity for BBOX inhibition over representative human 2OG oxygenases, including PHD2. The Desidustat derivatives will help to enable investigations into the biological roles of l-carnitine and the therapeutic potential of BBOX inhibition."

Journal • Cardiovascular

Revolutionizing anemia management in dialysis: unveiling the potential of FDA-approved Vadadustat for chronic kidney disease (CKD) patients. (PubMed, Ann Med Surg (Lond)) - No abstract available

FDA event • Journal • 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=500 | Not yet recruiting | Sponsor: Akebia Therapeutics

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

Akebia Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Vafseo (vadadustat) Commercial Launch Progress Update (GlobeNewswire) - "Akebia Therapeutics, Inc...As previously announced, Vafseo (vadadustat) shipments to customers began January 9, 2025. Akebia expects Vafseo first quarter 2025 net product revenues of approximately $10-$11 million...We expect to initiate the VALOR study in the second half of this year...Auryxia (ferric citrate) net product revenues were $44.4 million in the fourth quarter of 2024 compared to $53.2 million in the fourth quarter of 2023, and $152.2 million for the full-year 2024 compared to $170.3 million for the full-year 2023."

Commercial • Launch US • New P3 trial • Sales projection • Anemia • Chronic Kidney Disease • Hematological Disorders • Renal Disease

Cardiovascular Risk in Patients With DD-CKD Randomized to Vadadustat vs Darbepoetin Alfa With or Without Cardiovascular Disease (NKF-SCM 2025) - "In patients with a history of CV disease, the hazard ratio (HR) for MACE was 0.95 (95% CI: 0.80, 1.13) and for patients without a history of CV disease, HR for MACE was 1.00 (95% CI: 0.77, 1.30). Secondary safety outcomes were similar ( Figure ).Conclusion CV risk with VADA was similar to DA irrespective of baseline CV disease history."

Clinical • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Hematological Disorders • Myocardial Infarction

Vadadustat for Treatment of Anemia in Older vs Younger Patients With Dialysis-Dependent-CKD (NKF-SCM 2025) - "In ph3 trials of patients with DD-CKD (INNO 2 VATE), VADA was noninferior to darbepoetin alfa (DA) in time to first major adverse cardiovascular event (MACE: a composite of all-cause mortality, nonfatal MI, and nonfatal stroke) and hemoglobin (Hb) correction/maintenance. NI for both primary safety (MACE) and efficacy was met in each of the 2 age strata. In patients <65y, incidence of TEAEs was 87% vs 88%, and ≥65y it was 89% vs 91% in VADA vs DA, respectively.Conclusion In post hoc analyses, safety and efficacy of VADA were noninferior to DA irrespective of age stratum."

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

Akebia Therapeutics Announces Poster Presentations at NKF Spring Clinical Meetings 2025 (GlobeNewswire) - "Akebia Therapeutics, Inc...today announced that it will present data at the National Kidney Foundation Spring Clinical Meetings 2025 (NKF SCM25), which will take place in Boston, MA from April 10-13, 2025....On Thursday, April 10, 2025 at 4:00 pm during Oral Poster Presentation: Research 3 at NKF SCM25, Dr. Wolfgang Winkelmayer will present a poster titled 'Vadadustat for Treatment of Anemia in Older vs Younger Patients With Dialysis-Dependent-CKD.'"

Clinical data • Chronic Kidney Disease

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Non-Dialysis Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Indian J Nephrol) - "The studies included roxadustat (n = 2), daprodustat (n = 3), molidustat (n = 3), vadadustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Broadly, HIF-PHI molecules exhibited little difference when compared to other alternatives like erythropoietin stimulating agents (ESAs), but the evidence is not of high certainty. Our meta-analysis provides evidence on the use of HIF-PHIs as an alternative to ESAs for anemia in NDD-CKDs."

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

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Dialysis-Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Indian J Nephrol) - "The studies included roxadustat (n = 9), daprodustat (n = 5), vadadustat (n = 2), molidustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Roxadustat increased treatment-emergent adverse events up to 6-52 weeks as compared to ESAs [OR: 1.45 (95% CI 1.08-1.96); p = 0.01; six studies; 1715 participants; moderate certainty evidence]. The study provided evidence on the use of HIF-PHIs for treating renal anemia in DD-CKD patients as an alternative to ESAs."

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

Recommendations [Google translation] (Danish Medicines Council) - "The Danish Medicines Council recommends exagamglogene autotemcel (exa-cel) for the treatment of severe sickle cell disease (SCD) in patients ≥ 12 years of age with recurrent episodes of pain (vaso-occlusive crises, VOC) for whom hematopoietic stem cell transplantation is suitable and where a human leukocyte antigen-matched related stem cell donor is not available...The Danish Medicines Council recommends exagamglogene autotemcel (exa-cel) for the treatment of the blood disease transfusion-dependent β-thalassemia (TDT) in patients ≥ 12 years of age for whom hematopoietic stem cell transplantation is suitable and where a human leukocyte antigen-matched related donor is not available....The Danish Medical Council recommends vadadustat for the treatment of symptomatic anemia (anemia) associated with chronic kidney disease (CKD) in adults on chronic maintenance dialysis."

Reimbursement • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Sickle Cell Disease

Vadadustat (Vafseo) for anemia of chronic kidney disease. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Nephrology: what's new in 2024 (I) (PubMed, Rev Med Suisse) - "From immunoglobulin A nephropathy to primary focal segmental glomerulosclerosis, sparsentan expands its indications. Vadadustat represents an oral alternative for the treatment of renal anemia. Xenotransplantation offers a glimpse of a future without organ shortages."

Journal • Diabetes • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

Bioanalysis, Analysis, Chemistry, and Pharmacological Aspects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors. (PubMed, Curr Top Med Chem) - "The development of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIFPHIs), such as Roxadustat (ROX), Enarodustat (ENA), Desidustat (DES), Vadadustat (VAD), Molidustat (MOL), and Daprodustat (DAP), has significant effects on anemia in chronic kidney disease. Research indicates that most studies concentrate on hyphenated methodologies for drug estimation in various biological fluids. Consequently, this study assesses the biological efficacy of HIF-PHIs and elucidates the analytical methodologies currently employed for measurement across various matrices."

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

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in Sprague Dawley Rats (ASH 2024) - "BackgroundInhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PH) by oral small molecules has been intensively pursued in treating chronic kidney disease (CKD) anemia during the past 20 years, leading to approval of daprodustat and vadadustat by FDA in treating dialysis-dependent (DD) CKD anemia in US while both plus roxadustat failed in getting approval by FDA in treating non-dialysis dependent (NDD) CKD anemia in US due to safety concerns. The hematocrits (%) for group 1 to 4 were between 38.7 and 39.1 on day 1, were 41.7±1.5, 44.0±2.0, 48.6±2.5**, and 57.9±2.7** respectively on day 28, and were 42.5±1.4, 41.7±1.5, 43.6±1.5, and 41.9±0.9 respectively on day 56. (Significance analysis was compared to group 1,* p<0.05,** p<0.01)ConclusionRBC, HGB, and HCT in normal SD male rats were significantly increased after dosing AND017 at 2.5 and 5 mg/kg PO QD for 4 weeks and gradually recovered to background levels after..."

Preclinical • Anemia • Beta-Thalassemia • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • MYC

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in a Rat 5/6 Nephrectomy Model (ASH 2024) - "BackgroundTwo hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI), daprodustat and vadadustat, have been approved by FDA to treat dialysis dependent (DD) chronic kidney disease (CKD) anemia patients in US while all HIF-PHIs failed in getting approval by FDA in treating non-dialysis dependent (NDD) CKD anemia in US due to safety concerns. The hematocrits (%) for 5 groups were between 38.2±1.5 and 39.4±2.0 on day 1, were 41.6±1.6**, 36.3±1.9, 36.3±1.4, 37.2±1.2, and 36.3±1.7 respectively on day 35, were 41.8±1.3**, 36.8±2.4, 39.4±1.9*, 43.9±1.4**, and 51.4±2.8** respectively on day 49, and were 41.0±1.2**, 35.2±2.3, 39.0±3.6*, 45.7±3.1**, and 59.1±3.7** respectively on day 63. (Significance analysis was compared to group 2,* p<0.05,** p < 0.01)ConclusionThe rat 5/6 nephrectomy CKD anemia model was successfully established; on day 63, RBC, HGB, and HCT for rats in three..."

Preclinical • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • MYC