Studies Find Encouraging Safety Data With Vadadustat for Patients With Anemia Due to Chronic Kidney Disease
The FDA is currently reviewing a New Drug Application for vadadustat in this patient population, and a Prescription Drug User Fee Act date has been set for March 29, 2022.
Several posters at the American Society of Nephrology 2021 Kidney Week reinforce positive safety data with the use of vadadustat in patients with anemia due to chronic kidney disease (CKD), according to a press release from Akebia.1
The FDA is currently reviewing a New Drug Application for vadadustat in this patient population, with a Prescription Drug User Fee Act (PDUFA) date set for March 29, 2022. According to the press release, there are currently no approved hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) approved to treat anemia due to CKD, so if approved, this would be a first-in-class drug.1
“We are within 5 months of vadadustat’s PDUFA date, which has the potential to be a pivotal catalyst for the company and, if approved, would mean the availability of a novel, oral therapeutic for people living with anemia due to chronic kidney disease,” said John P. Butler, CEO of Akebia Therapeutics, in the press release.1
In an analysis of pooled safety data from 4 global phase 3, randomized, open-label studies evaluating the use of vadadustat compared with darbepoetin alfa (DA), researchers found that vadadustat had a comparable treatment-emergent adverse event (TEAEs) profile compared to DA. The most common adverse events (AEs) in the vadadustat and DA groups were infections and infestations (50.8% and 52.7%, respectively); gastrointestinal disorders (40.2% and 35.2%, respectively); metabolism and nutrition disorders (34.6% and 36.2%, respectively); and injury, poisoning, and procedural complications (29.5% and 30.7%, respectively).2
Furthermore, the most common drug-related TEAEs in the vadadustat group were diarrhea (2.2%) and nausea (1.2%), which led to study drug discontinuation in 0.4% and 0.2% of patients, respectively. The most frequent serious AEs in both treatment arms were infections and renal and urinary disorders, and TEAEs leading to death in both arms were cardiac arrest (1.7% in each group), end-stage kidney disease (1.8% and 1.3%, respectively), and cardio-respiratory arrest (0.9% and 1%, respectively).2
A second poster reviewed data demonstrating that among patients receiving peritoneal dialysis in the INNO2VATE phase 3 trials, the safety and efficacy of vadadustat were comparable with DA. Of 3923 patients randomized in the trials, 309 were receiving peritoneal dialysis, among whom the composite rates of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke were similar in both treatment groups.3
Primary and key secondary endpoints met the prespecified noninferiority margin, and the incidence of overall TEAEs was 88.2% in the vadadustat arm and 95.5% in the DA arm. Similarly, the incidence of serious TEAEs was 52.6% in the vadadustat arm and 73.2% in the DA arm.3
Finally, among patients in the phase 3 INNO2VATE trial with anemia and dialysis-dependent CKD, the rate of thrombotic events was similar between both the vadadustat and DA treatment arms, according to a third poster. A total of 1947 patients received vadadustat, whereas 1955 received DA in the 2 studies.4
According to the poster, a first thromboembolic event occurred in 169 patients in the vadadustat arm compared to 148 patients in the DA arm. Furthermore, 26 patients experienced arterial thrombosis, deep venous thrombosis, or pulmonary embolism in the vadatustat arm, compared with 32 patients in the DA arm. Finally, the number of patients who experienced venous thromboembolic events were 19 and 28, respectively.4
“While our review with the FDA is ongoing, we remain confident that the data we have compiled and submitted for review makes a compelling case for approval in dialysis patients,” Butler said in the press release.1
1. Vadadustat HIF-PHI Data at ASN. News release. November 4, 2021. Accessed November 4, 2021. Email.
2. Agarwal R, Vargo D, Luo W, Solinsky C, Chertow G. Comprehensive Safety Profile of Vadadustat from Global Phase 3 Clinical Trials. Poster; American Society of Nephrology 2021 Kidney Week. Accessed November 4, 2021. https://asn.apprisor.org/epsAbstractASN.cfm?id=1
3. Chertow G, Boudville N, Chowdhury P, Gonzalez C, et al. Vadadustat for Treatment of Anemia in Patients with Dialysis-Dependent CKD Receiving Peritoneal Dialysis. Poster; American Society of Nephrology 2021 Kidney Week. Accessed November 4, 2021. https://asn.apprisor.org/epsAbstractASN.cfm?id=1
4. Parfrey P, Luo W, Maroni B, Anders R, et al. Thromboembolic Events with Vadadustat vs. Darbopoetin Alfa for Anemia Treatment in Patients with Dialysis-Dependent CKD. Poster; American Society of Nephrology 2021 Kidney Week. Accessed November 4, 2021. https://asn.apprisor.org/epsAbstractASN.cfm?id=1