Five phase 3 ASCEND studies have shown positive results in the evaluation of the efficacy and safety profile of daprodustat (GlaxoSmithKline). The drug is an investigational oral hypoxia-inducible factor prolyl hydroxylase (HIF-PHI) inhibitor for patients with anemia due to chronic kidney disease (CKD).
CRF, characterized by progressive loss of kidney function, is a growing global health problem. Risk factors include hypertension, diabetes, obesity, and primary kidney disease, and CRF itself is an independent risk factor for cardiovascular disease. Anemia is a common complication of CRF, but it is often misdiagnosed and undertreated in patients with early-stage CRF who are often not on dialysis. CKD anemia is associated with poor clinical outcomes when left untreated.
According to the researchers, daprodustat met its primary endpoint in each study, demonstrating improvement in hemoglobin (Hgb) levels in untreated patients. Daprodustat also maintained Hgb levels in patients treated with an erythropoietin stimulating agent (ESA), a standard treatment option for patients with anemia due to CRF. In addition, studies for patients not on dialysis (ASCEND-ND) and on dialysis (ASCEND-D) demonstrated that daprodustat was non-inferior compared to ESA in the risk of major adverse cardiovascular events (MACE), the endpoint primary assessment of the two studies. .
The ASCEND program also included studies focusing on incident dialysis, for patients starting dialysis (ASCEND-ID); quality of life measures (ASCEND-NHQ); as well as 3 times weekly dosing regimens (ASCEND-TD), each of which met their respective primary or co-primary endpoints.
“I am particularly pleased with the results of the ASCEND-ND and ASCEND-D studies given the importance of managing cardiovascular outcomes for patients who currently have anemia due to chronic kidney disease, as well as the need to provide a practical oral treatment. treatment option, ”said Hal Barron, MD, Scientific Director and President of R&D at GSK, in a press release“ We will continue to analyze data from the strong ASCEND Phase 3 program and look forward to working closely together with regulators as we plan for our submissions.
In all ASCEND trials, daprodustat was generally well tolerated in non-dialysis and dialysis patients. Adverse events (AEs) occurring during treatment were similar in incidence rate between treatment groups and the nature of the events reported was consistent with the underlying patient population. The most frequently reported AEs in patients receiving daprodustat in the ASCEND program included hypertension, diarrhea, hypotension due to dialysis, peripheral edema, and urinary tract infections.
GSK announces positive results from five phase 3 studies of daprodustat in patients with anemia due to chronic kidney disease [news release]. GSK; July 16, 2021. Accessed July 20, 2021. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-daprodustat-phase-3-headline-results/