OLYMPUS is a Phase III, randomized, double blind, placebo-controlled trial designed to evaluate the efficacy and safety of roxadustat vs. placebo for the treatment of … Sun C.H. Occurrence of ≥1 drug-related AE was reported in 25.4% of vadadustat-treated patients (35 of 138) and 11.1% of placebo-treated patients (8 of 72). Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95 % CI, 0.06-2.59]; roxadustat, 0.40 (0.06-2.84); enarodustat, 0.33 (0.01-16.25); desidustat, 0.34 (0.01-17.00); epoetin, 0.50 (0.18-1.42); daprodustat, 0.54 (0.09-3.31); darbepoetin, 1.03 (0.65-1.65); and vadadustat, 1.43 (0.15-13.27)). et al. 64 In an open-label phase 2b trial of roxadustat, the most frequent AE (10%) was hypertension requiring a modification to antihypertensive medication. Vadadustat is the least potent inhibitor of PHD2, as the concentration needed to inhibit 50% of its activity in vitro (IC50) is the highest among the four compounds. (89.5% vs 78.0%), decrease in […] Read More. Share This Article . About anaemia. We use cookies on this website. With vadadustat nipping at roxadustat's heels, it would not be surprising to see all parties involved give timelines a boost. Another oral HIF-PHI drug – AstraZeneca and FibroGen’s roxadustat– has already been approved in China for CKD anaemia.Additional competition could come from Akebia, which has a drug in the class called vadadustat in late-stage clinical testing that is licensed to Mitsubishi Tanabe Pharma in some Asian markets including Japan. Find out more. At weeks 24 to 36, vadadustat-treated patients demonstrated a mean Hb level of 10.36g/dL vs 10.53g/dL for darbepoetin alfa-treated patients. 21-23, 38 One of two RCTs of vadadustat reported increased incidence of hyperkalemia [7/138 (5%) vs 0/72 (0%) in vadadustat and control arms respectively]. Three of the four roxadustat RCTs reported higher incidence rates of hyperkalemia [26/250 (10%) vs 6/109 (5.5%) in roxdustat and control groups respectively]. See this table from a nice review Gupta et al, AJKD, 2017) for some key aspects of the different -dustats. Subsequently, as of August 2020, daprodustat and vadadustat become available, which are indicated for both patients on dialysis and those in pre-dialysis stage. Chronic kidney disease is a global public health challenge that affects approximately 10% of … Roxadustat demonstrated a mean increase from baseline in Hb levels, regardless of iron repletion, averaged over weeks 28 to 52 of 1.85 g/dL in pts treated with roxadustat vs. 0.13 g/dL with placebo (p<0.001). Download PDF. Blood. Currently, 3 oral compounds—daprodustat, roxadustat, and vadadustat—have advanced to global phase 3 development for patients with chronic kidney disease (CKD) patients not on dialysis. Related Topics. FibroGen has not even filed its AstraZeneca-partnered oral anemia drug roxadustat for U.S. regulatory approval. Shots: The P-III study involves assessing of Roxadustat (N=323) vs darbepoetin alfa (N=293) evaluating its safety and efficacy in (N=616) adult anemia patients with stage 3–5 chronic kidney disease (CKD) The study meet its 1EPs & 2EPs also demonstrated superiority, showing correction of hemoglobin levels during the first 24 wks. Vadadustat (INN; AKB-6548) is a drug which acts as a HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin, which stimulates production of hemoglobin and red blood cells.It is in Phase III clinical trials for the treatment of anemia secondary to chronic kidney disease.. See also. In September 2019, Astellas had obtained an MA in Japan for the first oral HIF-PH inhibitor, roxadustat, and intended to launch the product in the UK (and elsewhere). HIMALAYAS evaluated roxadustat vs. epoetin alfa in ID patients; there were ID patients in ROCKIES and SIERRAS. Interventions of interest included 6 kinds of HIF-PHIs (Roxadustat, Daprodustat, Vadadustat, Molidustat, Desidustat, and Enarodustat) and 2 ESAs (Epoetin and Darbepoetin), comparisons of these different drugs, as well as placebos. At the beginning, its indication was only limited to renal anemia in patients on dialysis. No serious adverse event related to the study drug was considered. Akebia Therapeutics. The proportion of patients achieving Hb response at 2 consecutive visits without rescue during the first 24 weeks was 77.0% with roxadustat vs 8.5% with placebo (P <.001). Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Anaemia can be a serious medical condition in which patients have insufficient red blood cells and low levels of haemoglobin, a protein in red blood cells that carries oxygen to cells throughout the body. Abstract; Full Text ; Full Text PDF; Scopus (103) Google Scholar; In 2 dose-finding studies, Provenzano et al. The case began when Akebia and Otsuka sought to ‘clear the way’ for their HIF-PH inhibitor, vadadustat (which is currently in Phase III clinical trials). 2016; 90: 1115-1122. Vadadustat starting doses of 300 mg QD, 450 mg QD, and 450 mg TIW maintained mean Hb concentrations, from pre-baseline values to Weeks 7–8 and 15–16 in the prespecified primary efficacy analysis using observed data. There is a variety of reasons why trials in pediatric CKD patients may differ from adults. Roxadustat Treatment for Anemia in Dialysis This randomized, phase 3 trial compared the effectiveness of roxadustat, an oral hypoxia-inducible factor … Provenzano R. Besarab A. The outcomes included a change in Hb levels from baseline (ΔHb) and all-cause mortality. Vadadustat (INN) (AKB-6548) is a drug which acts as a HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin, which stimulates production of hemoglobin and red blood cells.It is in Phase III clinical trials for the treatment of anemia secondary to chronic kidney disease. Daprodustat, Roxadustat, Vadadustat, and Molidustat are discussed in greater detail below. Kidney Int. A mean blood pressure reduction of 2.6 ± 9.6 mm Hg from baseline was observed in the phase 2b trial of 16 and 24 weeks of treatment with roxadustat. These experimental hypoxia-inducible factor prolyl hydroxylase inhibitors, roxadustat and vadadustat, aim to stimulate the body's endogenous erythropoietin, and have the advantage of being oral rather than infused intravenously as with the ESAs. Quality confirmed by NMR & HPLC. WARNINGS AND PRECAUTIONS. AURYXIA ® (ferric citrate) is contraindicated in patients with iron overload syndromes, e.g., hemochromatosis. CONTRAINDICATION. QUICK TAKE Roxadustat for Anemia in Chronic Kidney Disease 01:53. Vadadustat Vs Roxadustat From the randomized phase III study GOG 240, the US Food and Drug Administration (FDA) authorized the very first anti-angiogenic agent, bevacizumab (Avastin, Genentech/Roche), in mixture with chemotherapy for use in ladies with sophisticated cervical cancer [8]. Pooled MACE/MACE+ in DD patients. The rates of serious adverse events were 13.0% in the vadadustat group and 10.6% in the DA group. Vadadustat exploits the same mechanism of action used by the body to adapt naturally to lower oxygen availability associated with a moderate increase in altitude. Related Companies. PYRENEES was not included in the pooled CV safety analyses. To pass the regulators, however, roxadustat and vadadustat will need to show that they are at least as safe as ESAs. 5. Trial Results. Roxadustat is one of several prolyl-hydroxylase inhibitors (PHI), along with daprodustat, vadadustat, desidustat, and molidustat, that act by inhibiting hypoxia-inducible factor prolyl hydroxylase, stabilising HIF-α, increasing erythropoietin, and preventing its breakdown. AEs in both treatment groups were primarily mild or moderate in severity. In the vadadustat group, the most common adverse events were nasopharyngitis (19.8% vs 28.6% in the DA group), diarrhea (10.5% vs 9.9% in the DA group), and shunt stenosis (8.0% vs 12.4% in the DA group). FibroGen. Roxadustat is an emerging and promising therapeutic approach against anemia in CKD patients, which differs from those of conventional ESAs. Moreover, vadadustat … By using this site, you agree that we may store and access cookies on your device. In November 2019, the novel drug for renal anemia, Roxadustat, became available for the first time in Japan. ID patients are a better population to compare roxadustat vs. epoetin alfa than the stable dialysis population, where patients are stable not only on dialysis but also on erythropoietin. Vadadustat Performance vs. SOC ESA1 Roxadustat Statistically non-inferior HR=0.96 Statistically non-inferior HR=0.96 Statistically significant INCREASE p=0.001 Statistically significant DECREASE p = 0.0000003 • Both Fibrogen’s Roxadustat and Akebia’s Vadadustat were shown tobe non-inferior standard of care (ESA) with respect to the MACE outcome endpoint. Astellas (roxadustat), Akebia (vadadustat), GlaxoSmithKline (daprodustat), and Bayer (molidustat) have all deferred pediatric studies until phase III trials have been completed, which will allow changes to be made to the design of proposed studies, if needed. Vadadustat (AKB-6548, B-506, PG-1016548) is a novel, titratable, oral HIF-PH inhibitor. See customer reviews, validations & product citations. Phase III. The percentage of patients who experienced ≥1 adverse event (AE) was comparable between the vadadustat and placebo groups (74.6% vs. 73.6%) . Vadadustat is an oral, investigational hypoxia-inducible factor (HIF) stabilizer currently in Phase 3 development for the treatment of anemia related to chronic kidney disease.