Positive Headline Results Reported From 5 Studies of Daprodustat in Patients with Anemia From Chronic Kidney Disease
Five studies from the phase 3 ASCEND program showed positive headline results in evaluating the efficacy and safety profile of daprodustat (GlaxoSmithKline). The drug is an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for patients with anemia due to chronic kidney disease (CKD).
CKD, characterized by progressive loss of kidney function, is a growing global health concern. Risk factors include hypertension, diabetes, obesity, and primary renal disorders, and CKD is itself an independent risk factor for cardiovascular disease. Anemia is a frequent complication from CKD, but it is often poorly diagnosed and undertreated in patients with early-stage CKD who are often not on dialysis. Anemia from CKD is associated with poor clinical outcomes when left untreated.
According to the investigators, daprodustat met its primary efficacy endpoint in each study, demonstrating an 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 from CKD. Further, studies for non-dialysis (ASCEND-ND) and dialysis patients (ASCEND-D) demonstrated that daprodustat was non-inferior when compared to an ESA in the risk of major adverse cardiovascular events (MACE), the primary endpoint of both studies.
The ASCEND program also included studies focused on incident dialysis, for patients just starting dialysis (ASCEND-ID); quality of life measures (ASCEND-NHQ); as well as 3-times weekly dosing regimens (ASCEND-TD), each of which met its respective primary or co-primary endpoints.
“I am particularly pleased with the results from the ASCEND-ND and ASCEND-D studies given the importance of managing cardiovascular outcomes for patients who are currently suffering from anemia due to chronic kidney disease, as well as the need to provide a convenient, oral treatment option,” said Hal Barron, MD, chief scientific officer and president of R&D at GSK, in a press release “We will continue to analyze the data from the robust phase 3 ASCEND program and look forward to working closely with regulators as we plan for our submissions.”
Across all of the ASCEND trials, daprodustat was generally well tolerated in both non-dialysis and dialysis patients. Treatment-emergent adverse events (AEs) were similar in incidence rate between treatment groups and the nature of reported events was consistent with the underlying patient population. The most frequently reported AEs for the patients receiving daprodustat across the ASCEND program included hypertension, diarrhea, dialysis hypotension, peripheral edema, and urinary tract infection.
GSK announces positive headline results from five Phase 3 studies of daprodustat for patients with anaemia 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/