It is in Phase III clinical trials for the treatment of anemia secondary to … Adverse events considered serious included cerebral infarction, occurring in 0.4% of patients, and shunt occlusion, occurring in 1% of patients (the Japanese prescribing information contains a warning about the risk of thromboembolism). PubMed Google Scholar. Chem Sci. LSM change in haemoglobin levels from the pretreatment level to week 6 were − 0.28, 0.08, 0.41 g/dL in the vadadustat 150, 300, and 600 mg/day groups compared with − 1.48 g/dL in the placebo group (all p < 0.001 vs. placebo). Akebia Therapeutics Inc. Akebia and Mitsubishi Tanabe Pharma announce collaboration to develop and commercialize vadadustat in Asia [media release]. Am J Kidney Dis. Informations sur votre appareil et sur votre connexion Internet, y compris votre adresse IP, Navigation et recherche lors de l’utilisation des sites Web et applications Verizon Media. US Securities and Exchange Commission. Ltd. About Us; History; Our Team; Company Profile Am J Kidney Dis. BPRL PRIVATE LIMITED | Herbal Division | Super speciality Division . 327]. Vadadustat: First Approval Vadadustat (VAFSEO^®) is a prolyl hydroxylase inhibitor being developed by Akebia Therapeutics, Inc. (Akebia) for the treatment of anaemia associated with chronic kidney disease (CKD). Article  Vadadustat received its first approval on June 29 2020 for anaemia associated with CKD in Japan [4]. 2019;30:212. Vadadustat is in global Phase 3 development for the treatment of anemia due to CKD and is not approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority with the exception of Japan's Ministry of Health, Labour and Welfare (MHLW). 5 May 2020. https://akebia.com/. Mitsubishi Tanabe Pharma Corporation. TH-PO369]. © 2021 Springer Nature Switzerland AG. Vadadustat was noninferior to darbepoetin alfa in the time to first MACE (HR 0.96; 95% CI 0.83–1.11) in a combined analysis of data from both INNO2VATE trials [6]. Eighty, 73 and 68% of patients in the 300 mg once daily, 450 mg once daily, and 450 mg thrice weekly cohorts, respectively, completed the study. Sanghani NS, Haase VH. Drugs 80, 1365–1371 (2020). The least square mean (LSM) average haemoglobin level at weeks 20 and 24 (primary endpoint) was 11.66 g/dL (95% CI 11.49–11.84 g/dL) in the vadadustat group compared to 11.93 g/dL (95% CI 11.76–12.10 g/dL) in darbepoetin alfa recipients (LSM difference between groups − 0.26 g/dL (95% CI − 0.50 to − 0.02). The mean haemoglobin level between weeks 40 and 52 was 10.51 g/dL in the vadadustat group versus 10.55 g/dL in darbepoetin alfa recipients (LSM difference between groups − 0.07 g/dL; 95% CI − 0.34 to 0.19) [6]. PubMed  The lower limit of the 95% confidence interval was above the predefined noninferiority margin of − 0.75 g/dL. 90.9% of patients who had received vadadustat for 16 weeks had a haemoglobin level within the target range of 10–12 g/dL. Vadadustat is primarily metabolized by glucuronidation and O-glucuronic acid conjugates accounted for a further ≈ 15% of radioactivity [5]. The LSM average haemoglobin at weeks 20 and 24 (primary endpoint) was 10.61 (95% CI 10.45–10.76 g/dL) in the vadadustat group compared to 10.65 g/dL (95% CI 10.50–10.80 g/dL) in the darbepoetin alfa group, with the 95% confidence interval of both groups within the target range of 10–12 g/dL. Découvrez comment nous utilisons vos informations dans notre Politique relative à la vie privée et notre Politique relative aux cookies. Akebia Therapeutics Inc. Akebia and Otsuka Pharmaceutical announce collaboration to develop and commercialize vadadustat in the U.S. [media release]. BPRL Pvt. The results of the pre-specified subgroup analyses will be a positive addition to the dataset submitted for review by the FDA and could bolster vadadustat’s FDA approval chances. Sawant R, Paulson S, Burke L, et al. 14 Dec 2015. https://akebia.com/. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy, Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand, You can also search for this author in 2017;45(5):380–8. 15 May 2017. https://akebia.com/. Reticulocytes levels and total iron-binding capacity were significantly increased and serum hepcidin and ferritin levels were significantly decreased in vadadustat recipients compared to the placebo group [21]. The phase II FO2WARD-2 trial (NCT03799627) is an efficacy, safety and pharmacokinetic/pharmacodynamic study evaluating vadadustat for the treatment of anaemia in patients on haemodialysis converting from epoetin alfa. Article  Vadadustat is an investigational therapy and is not approved by the U.S. Food and Drug Administration (FDA). Article  J Am Soc Nephrol. In the per-protocol population, 54.9% of patients on vadadustat and 10.3% of patients on placebo achieved or maintained either a mean haemoglobin level of  ≥ 11.0 g/dL or a mean increase in haemoglobin of ≥ 1.2 g/dL over the predose average during the last 2 weeks of treatment (primary endpoint). Akebia Therapeutics (AKBA) Announces Approval of Vadadustat in Japan for Treatment of Anemia Due to CKD. PubMed Central  Treatment with vadadustat was associated with increased haemoglobin levels and improved biomarkers of iron mobilization and utilization in a double-blind, placebo-controlled phase II trial (NCT01381094) in patients with anaemia secondary to stage 3 or 4 CKD conducted in the USA [20]. Employee Login . Within Japan, Vadadustat is approved as a treatment for anemia due to CKD in both dialysis-dependent and … During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Article  Nangaku M, Kondo K, Kokado Y, et al. Clinical trial of vadadustat in patients with anemia secondary to stage 3 or 4 chronic kidney disease. Randomized, open-label, active-controlled (darbepoetin alfa), phase 3 study of vadadustat for treating anemia in non-dialysis-dependent CKD patients in Japan [abstract no. Significant, dose-dependent changes in biomarkers of iron utilisation and mobilization (total iron binding capacity increased; transferrin saturation, mean absolute ferritin and hepcidin decreased) were evident after 16 weeks of vadadustat treatment in all groups. While total iron binding capacity significantly increased and mean absolute ferritin significantly decreased after 16 weeks of vadadustat treatment across all groups, changes in transferrin saturation and hepcidin (apart from in the vadadustat 150 mg/day arm) were not significant [19]. Anthony Markham. The primary safety endpoint was the time to first occurrence of MACE (major cardiovascular events; MACE is a composite endpoint of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke); noninferiority was achieved if the upper bound of the 95% confidence interval for the hazard ratio of vadadustat to darbepoetin alfa did not exceed 1.25 (US FDA requirement) or 1.3 (EMA requirement) [6]. 4 Jan 2016. https://akebia.com/. Mitsubishi Tanabe Pharma Corporation. 2020. https://doi.org/10.1093/ndt/gfaa060. SKYPE. This profile has been extracted and modified from the AdisInsight database. Impaired renal or hepatic function had no clinically relevant effect on the pharmacokinetic profile of vadadustat [5, 15] and there were no clinically relevant changes in exposure to vadadustat when the drug was administered with food [16]. Part of Springer Nature. No statistically significant mean change in haemoglobin levels from the pre-baseline average to mid-trial (primary endpoint) was observed in any of the three groups [22]. Akebia Therapeutics®, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, today announced the first regulatory approval … Vadadustat was also associated with significant decreases in ferritin at all dose levels and hepcidin levels at doses of 370, 500, and 630 mg/day (p < 0.05) [20]. The trial was evaluating the company’s vadadustat for treatment of anemia caused by chronic kidney disease in adults not on dialysis. Haase VH, Chertow GM, Block GA, et al. Randomized, double-blinded, active-controlled (darbepoetin alfa), phase 3 study of vadadustat in CKD patients with anemia on hemodialysis in Japan [abstract no. Mean haemoglobin levels between weeks 40–52 (secondary endpoint) were 10.40 and 10.58 g/dL in the vadadustat and darbepoetin alfa groups, respectively (LSM difference between groups − 0.18 g/dL; 95% CI − 0.25 to − 0.12) [6]. Nephrol Dial Transplant. The difference in LSM haemoglobin levels between the two groups was − 0.05 g/dL (95% CI − 0.26 to 0.17) with the lower limit of the 95% confidence interval exceeding the predefined noninferiority margin of − 0.75 g/dL. Enhanced material for this AdisInsight Report can be found at https://doi.org/10.6084/m9.figshare.12782549. The baseline haemoglobin level in both treatment arms was 10.7 g/dL. May 15 (Reuters) - Akebia Therapeutics Inc * Akebia and Vifor Pharma announce exclusive license agreement to provide vadadustat to Fresenius Medical Care in the U.S. upon FDA approval RIIX WAA SKYPEGA taysiirulquraan Skype Fadliga Quranka SA-PO229]. Bloomberg the Company & Its Products The Company & its Products Bloomberg Terminal Demo Request Bloomberg Anywhere Remote Login Bloomberg Anywhere Login Bloomberg Customer Support Customer Support Action Date Submission Supplement Categories or Approval Type Letters, Reviews, Labels, Patient Package Insert Note Url; 01/28/2021: SUPPL-36: Labeling-Package Insert, Labeling-Medication Guide Akebia Therapeutics Inc. Akebia closes $41 million Series C [media release]. Vadadustat significantly increased mean haemoglobin levels at week 6 compared with placebo in Japanese patients (n = 51) with non-dialysis-dependent CKD in a 16-week, phase II dose-finding trial (NCT03054337) and by week 16 of treatment, almost all vadadustat recipients achieved target haemoglobin levels [19]. Yahoo fait partie de Verizon Media. 2019;26(4):253–66. Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized phase 2 trials in Japanese patients. It is subject to approval of vadadustat by the FDA and inclusion of vadadustat in a bundled reimbursement model, upon which Akebia will receive a $20 million payment from Vifor Pharma. Zuk A, Si Z, Loi S, et al. 10 Mar 2020. https://akebia.com/. The O-glucuronic acid conjugate metabolite of the drug is a substrate of OAT3 and has an inhibitory effect on OAT3. 20 Dec 2016. https://akebia.com/. 2019;30:825. J Am Soc Nephrol. Akebia Therapeutics Inc. Akebia and Vifor Pharma announce exclusive license agreement to provide vadadustat to Fresenius Medical Care in the U.S. upon FDA Approval [media release]. 71.4% of patients who had received vadadustat for 16 weeks had a haemoglobin level within the target range of 10–12 g/dL. Google Scholar. A. Markham is a contracted employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. https://doi.org/10.1007/s40265-020-01383-z, DOI: https://doi.org/10.1007/s40265-020-01383-z, Over 10 million scientific documents at your fingertips, Not logged in It is subject to approval of vadadustat by the FDA and inclusion of vadadustat in a bundled reimbursement model, upon which Akebia will receive a $20 million payment from Vifor Pharma. In the global INNO2VATE program in patients with dialysis-dependent CKD, the most common adverse events with vadadustat or darbepoetin were hypertension (16.2% vs 12.9%) and diarrhoea (10.1% vs 9.7%) in INNO2VATE-correction/conversion (n = 181 and 188) and diarrhoea (13.0% vs 10.1%), pneumonia (11.0% vs 9.7%), hypertension (10.6% vs 13.8%) and hyperkalemia (9.0% vs 10.8%) in INNO2VATE- conversion (n = 1777 and 1777) [6]. On June 29, 2020, MTPC obtained approval of vadadustat as a treatment for anemia due to CKD in both dialysis-dependent and non-dialysis dependent adult patients. Pour autoriser Verizon Media et nos partenaires à traiter vos données personnelles, sélectionnez 'J'accepte' ou 'Gérer les paramètres' pour obtenir plus d’informations et pour gérer vos choix. Google Scholar. Accessed 21 Jul 2020. Manufacturing and marketing approval of VAFSEO® tablets (HIF-PH inhibitor, vadadustat) for renal anemia in Japan [media release]. According to the Japanese prescribing information, adverse events occurring in ≥ 1% but < 5% of patients treated with vadadustat in Japanese trials were hypertension, diarrhoea and nausea [5]. Hypoxia-inducible factor activators in renal anemia: current clinical experience. The LSM change in haemoglobin levels from pretreatment to week 6 was 0.43, 1.13 and 1.62 g/dL in the vadadustat 150, 300, and 600 mg/day groups versus − 0.47 g/dL in the placebo group (all p < 0.01 vs. placebo). After 16 weeks of treatment, changes in mean absolute haemoglobin from pretreatment levels in the respective vadadustat groups were 0.98, 1.61 and 1.78 g/dL, while that in patients who switched from placebo to vadadustat was 1.42 g/dL. 2019;30:8. … In INNO2VATE-correction/conversion, incident dialysis patients with end stage renal disease and limited exposure to recombinant ESAs were randomized to treatment with vadadustat (n = 181) or darbepoetin alfa (n = 188). The mean haemoglobin level between weeks 24 to 36 (primary efficacy) was 10.36 g/dL in vadadustat-treated patients compared to 10.61 g/dL in the darbepoetin alfa group (LSM difference between groups − 0.31 g/dL; 95% CI − 0.53 to − 0.10). Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. 0.70, 1.15 and 1.39 g/dL from baseline in the vadadustat 249, 370, 500 and 630 mg/day groups compared to a 0.06 g/dL reduction in the placebo group (all p < 0.05 vs. placebo and baseline). After 16 weeks of treatment, changes in mean absolute haemoglobin from pretreatment levels in the respective vadadustat groups were 1.40, 2.44 and 1.64 g/dL, while that in patients who switched from placebo to vadadustat was 1.87 g/dL. Pergola PE, Spinowitz BS, Hartman CS, et al. Patients were sequentially assigned to one of three vadadustat starting doses, 300 mg once daily (n = 30), 450 mg once daily (n = 33) or 450 mg thrice weekly (n = 31), all for 16 weeks. Vadadustat is in global Phase 3 development for the treatment of anemia due to CKD and is not approved by the U.S. Food and Drug Administration (FDA) or … Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents. Akebia Therapeutics Inc. Akebia and Otsuka expand relationship with collaboration to develop and commercialise vadadustat in Europe, China and other territories [media release]. Vadadustat improved mean haemoglobin levels from 10.68 g/dL at baseline to 11.27 g/dL at week 24 in patients converted from other ESAs (n = 80) and from 10.17 to 11.85 g/dL in patients who were not receiving ESAs at baseline (n = 71) [17]. Vadadustat is an investigational therapy and is not approved by the U.S. Food and Drug Administration (FDA). Akebia Therapeutics Form 10-K, March 2020. https://akebia.com/. Corporate News, FDA, Management Comments. https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400315_39990D3F1020_1_01, https://doi.org/10.6084/m9.figshare.12782549, https://doi.org/10.1007/s40265-020-01383-z, A prolyl hydroxylase inhibitor is being developed by Akebia Therapeutics, Inc. for the treatment of anaemia associated with chronic kidney disease, Received its first approval on June 29 2020 in Japan, Approved for use adult patients with anaemia associated with chronic kidney disease, Acetic acids, amides, anti-anaemics, chlorobenzenes, chlorophenols, pyridines, small molecules, Hypoxia-inducible factor-prolyl hydroxylase inhibitor, Pharmacokinetics (day 10; 300 mg once daily), 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid, Vadadustat, darbepoetin alfa, epoetin alfa. Akebia is collaborating with Mitsubishi Tanabe Pharma Corporation on the development and commercializatio … Markham, A. Vadadustat: First Approval. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Patients were randomized to 6 weeks’ treatment with oral vadadustat 240 (n = 18), 370 (n = 18), 500 (n = 17), or 630 mg (n = 19) once-daily or placebo (n = 19). Vadadustat will be marketed by MTPC in Japan under the trade name VAFSEO™. Vadadustat was noninferior to darbepoetin alfa in terms of the effects on haemoglobin levels and cardiovascular safety outcomes in the two phase III studies comprising the INNO2VATE cardiovascular outcomes program in patients with anaemia secondary to CKD who were dependent on dialysis. 2020. https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400315_39990D3F1020_1_01. In a further phase II trial (NCT02260193) conducted in the USA, vadadustat maintained mean haemoglobin concentrations in patients on haemodialysis who had previously received epoetin [22]. Sawant R, Paulson S, Burke L, et al. J Am Soc Nephrol. Patients with stages 3a to 5 non-dialysis-dependent CKD were randomized to 20 week’s treatment with vadadustat starting at 450 mg once daily and titrated to effect, or placebo. Vadadustat is an investigational therapy and is not approved by the U.S. Food and Drug Administration (FDA). Unchanged drug accounted for 75% of total radioactivity (AUC∞) in plasma after administration of a single oral 650 mg dose of radiolabelled vadadustat to healthy volunteers (n = 6). PubMed  Coadministration of vadadustat with the proton pump inhibitor rabeprazole was not associated with clinically relevant changes in vadadustat exposure [14]. 25 Apr 2017. https://akebia.com/. Patients were randomized to receive vadadustat (n = 162) or darbepoetin alfa (n = 161); vadadustat treatment was initiated at 300 mg/day and titrated between 150 mg/day and 600 mg/day to maintain a haemoglobin level of 10–12 g/dL. Those occurring in < 1% of patients included sleep disorders, somnolence, retinal haemorrhage, vertigo, palpitations, polycythaemia, abdominal discomfort, vomiting, loose stools, gastritis, gastroenteritis, stomatitis, rash, pruritus, eczema, erythema, alopecia, cold sweats, frequent urination, increased blood creatinine levels, malaise, chest discomfort, nipple pain and peripheral oedema [5]. FDA calendar is a useful tool to know PDUFA dates related to FDA Approval and FDA Panel review of New Drug Applications, which are catalysts of Biotech Stocks. 104 (75.4%) and 115 (75.7%) patients in the vadadustat and darbepoetin alfa groups, respectively, had haemoglobin levels within the target range at week 24 [18]. Akebia Therapeutics®, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, today announced the first regulatory approval of vadadustat, its oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), for the treatment of Preclinical characterization of vadadustat (AKB-6548), an oral small molecule hypoxia inducible factor prolyl-4-hydroxylase inhibitor, for the potential treatment of renal anemia [abstract no. Mean haemoglobin levels between weeks 24 to 36 (primary endpoint) were 10.36 and 10.53 g/dL in vadadustat and darbepoetin alfa recipients, respectively (LSM difference between groups − 0.17 g/dL; 95% CI − 0.23 to − 0.10). Roxadustat is under FDA review as an oral medicine to treat anemia caused by chronic kidney disease, both in patients who need dialysis and those who don't. Contact FDA Follow FDA on Facebook Follow FDA on Twitter View FDA videos on YouTube Subscribe to FDA RSS feeds FDA Homepage Contact Number 1-888-INFO-FDA (1-888-463-6332) Vadadustat was noninferior to darbepoetin alfa in controlling haemoglobin levels in Japanese patients with CKD not dependent on dialysis who were either switched from other erythropoiesis stimulating agents (ESAs) [conversion] or had not received ESAs (correction) in an open label phase III study (NCT03329196) [17]. Vadadustat is a substrate for organic anion transporters (OAT) 1 and 3, and has an inhibitory effect on breast cancer resistance protein (BCRP) and OAT3. Yeh TL, Leissing TM, Abboud MI, et al. 2017;8(11):7651–68. In a double-blind, randomized 16-week phase II trial in Japanese patients (n = 60) with haemodialysis-dependent CKD (NCT03054350) vadadustat significantly improved the mean haemoglobin change from pretreatment levels to week 6 compared with placebo (primary endpoint) [19]. The preparation of this review was not supported by any external funding. Vadadustat increased haemoglobin levels in a predictable and controlled manner and also enhanced iron mobilization in patients with nondialysis-dependent CKD in a double-blind, randomized, placebo-controlled, phase IIb study conducted in the USA (NCT01906489) [21]. All authors contributed to the review and are responsible for the article content. CAS  Nos partenaires et nous-mêmes stockerons et/ou utiliserons des informations concernant votre appareil, par l’intermédiaire de cookies et de technologies similaires, afin d’afficher des annonces et des contenus personnalisés, de mesurer les audiences et les contenus, d’obtenir des informations sur les audiences et à des fins de développement de produit. 2020;75(4):631. Vous pouvez modifier vos choix à tout moment dans vos paramètres de vie privée. Google Scholar. Akebia Therapeutics Inc. Akebia Therapeutics reports fourth quarter and full-year 2019 financial results and hosts conference call to discuss recent business highlights [media release]. The primary efficacy end point in both studies was the mean change in haemoglobin between baseline and the primary evaluation period (weeks 24–36); non-inferiority was achieved if the lower bound of the 95% confidence interval for the LSM difference between groups in the mean change in haemoglobin levels did not fall below − 0.75 g/dL. Kidney Int. Effect of moderate hepatic impairment on pharmacokinetics of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) [abstract no. Nangaku M, Farag YMK, de Goma E, et al. In this trial, patients were randomized to treatment with vadadustat 150 mg (n = 15), 300 mg (n = 15) and 600 mg (n = 14) or placebo (n = 14) once daily for 6 weeks, followed by a 10-week dose adjustment/maintenance phase (vadadustat dosages were adjusted to achieve a target haemoglobin of 10–12 g/dL; placebo recipients were switched to vadadustat 150, 300 or 600 mg/day) [19]. Nephrol Dial Transplant. 29 Jun 2020. http://www.mt-pharma.co.jp. The ongoing phase III PRO2TECT program in nondialysis-dependent CKD comprises two separate studies; PRO2TECT correction (NCT02648347) in patients with anaemia not currently being treated with recombinant ESAs, and PRO2TECT conversion (NCT02680574) in patients currently receiving recombinant ESAs who were switched to either vadadustat or active control [23]. 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. Coadministration with vadadustat increased the Cmax and AUC∞ of the BCRP substrates rosuvastatin, simvastatin, atorvastatin and salazosulfapyridine and the OAT3 substrate furosemide [5], but did not affect the exposure of the OATP1B1 substrate pravastatin or the OAT1 substrate adefovir [13]. Adv Chronic Kidney Dis. Akebia Therapeutics Inc. Akebia initiates phase 3 PRO2TECT(TM) Program [media release]. Vadadustat is an investigational drug that has not been approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority for use outside of Japan. - 213.219.39.6. In this randomized, double-blind trial, patients were randomized to treatment with vadadustat 150 mg (n = 12), 300 mg (n = 12) and 600 mg (n = 13) or placebo (n = 14) once daily for 6 weeks, followed by a 10-week dose adjustment/ maintenance phase (vadadustat dosages were adjusted to achieve a target haemoglobin of 10–12 g/dL; placebo recipients were switched to vadadustat 150, 300 or 600 mg/day). Hepatic dysfunction with elevated AST, ALT and total bilirubin levels may also occur [5]. PubMed Central  Chavan AB, Paulson SK, Burke L, et al. SA-OR037]. Nangaku M, Kondo K, Ueta K, et al. PubMed  In a double-blind, phase III study conducted in Japan (NCT03439137), vadadustat was as effective as darbepoetin alfa in maintaining haemoglobin levels in Japanese patients with CKD dependent on dialysis who were switched from other ESAs (conversion) [18]. Correspondence to Akebia Therapeutics Inc. Akebia Therapeutics announces positive top-line results from global phase 3 program of vadadustat for treatment of anemia due to chronic kidney disease in adult patients on dialysis [media release]. Mean haemoglobin levels increased 0.76. It is subject to approval of vadadustat by the FDA and inclusion of vadadustat in a bundled reimbursement model, upon which Akebia will receive a $20 million payment from Vifor Pharma. In INNO2VATE-conversion, patients on chronic dialysis who were receiving recombinant ESAs (n = 3554) were randomly switched to vadadustat or darbepoetin alfa (n = 1777 per cohort). -- Vifor Pharma Commits to Exclusive Distribution of Vadadustat to Fresenius Medical Care North America for Use in its Dialysis Facilities and Invests $50 Million in Akebia at a Premium -- -- Additional Funds Support Vadadustat Global Development Program to Data -- ZURICH, SWITZERLAND & CAMBRIDGE, MA, USA - 16 May 2017… 2016;90(5):1115–22. Coadministration of vadadustat with the OAT1 and OAT3 inhibitor probenecid was associated with increased AUC∞ of vadadustat and its O-glucuronic acid conjugate metabolite. 328]. h/mL; and mean t½ was 5.96, 6.14 and 6.07 h, respectively [5]. Am J Nephrol. 2019;30:90. Both trials in the INNO2VATE programme were multinational, multicentre studies comparing treatment with vadadustat (starting at 300 mg once daily, then titrated in increments of 150 mg within the range of 150–600 mg/day) to darbepoetin alfa (at the recommended dose). The drug was > 99% bound to human plasma protein in vitro [5]. Evaluation of drug interaction with multiple doses of rabeprazole, a proton pump inhibitor, on the pharmacokinetics of vadadustat [abstract no. J Am Soc Nephrol. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond. Patients were randomized to receive vadadustat (n = 151) or darbepoetin alfa (n = 153); vadadustat treatment was initiated at 300 mg/day and titrated between 150 mg/day and 600 mg/day to maintain a haemoglobin level of 11–13 g/dL. TH-OR024]. The PRV sets Vifor and partner Akebia Therapeutics up to benefit from a fast review at the FDA when they file for approval of chronic kidney disease drug vadadustat. CAS  Fadlan Riix Call Skype. INNO2VATE-conversion (NCT02892149) enrolled dialysis patients currently receiving recombinant ESAs who were then converted to either vadadustat or darbepoetin alfa [6]. Martin ER, Smith MT, Maroni BJ, et al. 2020;75(4):631. 2019;34(1):90–9. PubMed  Vadadustat is in global Phase 3 development for the treatment of anemia due to CKD and is not approved by the U.S. Food and Drug Administration (FDA… 4 Jun 2013. https://akebia.com/. A further phase III study (NCT04313153) is evaluating the efficacy and safety of vadadustat once daily and three times weekly for the maintenance treatment of anaemia in haemodialysis patients converting from ESAs. Action Date Submission Supplement Categories or Approval Type Letters, Reviews, Labels, Patient Package Insert Note Url; 02/24/2021: SUPPL-417: Efficacy-New Indication Google Scholar. In total, 60% surveyed US nephrologists anticipated an FDA approval for vadadustat, while 40% saw a US approval in this patient population as unlikely. Accessed 6 Aug 2020. Effect of food intake on the pharmacokinetics of vadadustat following single dose administration [abstract no. Akebia Therapeutics announced topline results for PRO2TECT, the second of two Phase III cardiovascular outcomes programs. INNO2VATE-correction/conversion (NCT02865850) enrolled incident dialysis patients who had initiated peritoneal dialysis or haemodialysis ≤ 16 weeks prior to screening and had limited exposure to recombinant ESAs. Akebia's revenue from the profit share and the milestone payment will be shared with Otsuka Pharmaceutical Co. Ltd., Akebia's U.S. collaborator. Vadadustat (VAFSEO ®) is a prolyl hydroxylase inhibitor being developed by Akebia Therapeutics, Inc. (Akebia) for the treatment of anaemia associated with chronic kidney disease (CKD). Vadadustat (VAFSEO tablets): Japanese prescribing information.