GSK starts phase III program with daprodustat for anemia associated with chronic kidney disease.
GlaxoSmithKline plc has announced the start of a phase III development program investigating daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), as a treatment for anemia associated with chronic kidney disease (CKD).
The phase III program includes two studies evaluating the safety and efficacy of daprodustat compared to recombinant human erythropoietin:
- ASCEND-D (Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis) will enroll approximately 3,000 dialysis dependent subjects with anemia associated with CKD switching from an erythropoietin-stimulating agent (ESA).
- ASCEND-ND (Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis) will enroll approximately 4,500 non-dialysis dependent subjects with anemia associated with CKD, and will include patients either switching from or naive to an ESA.
For both studies, the co-primary endpoints are time to first occurrence of major adverse cardiovascular events (MACE) and mean change in hemoglobin between the baseline and efficacy period (mean over Weeks 28-52). The studies will assess whether daprodustat is non-inferior to recombinant human erythropoietin on these endpoints as the primary analysis. If non-inferiority of the primary analysis is met, superiority will be assessed for the safety endpoint.
Julian Jenkins, vice president and medicine development leader responsible for the daprodustat programmed, said: “For many patients with chronic kidney disease, treating their anemia comes with risks associated with cardiovascular safety and injectable administration. The start of phase III studies of daprodustat is an important step in our work to explore whether daprodustat could address those risks and provide a potential alternative, oral treatment option.”
The design of the phase III programmed is based upon data from phase II clinical trials that were designed to characterize the dose-response relationship between daprodustat and hemoglobin at 4 weeks and assess the safety and tolerability of daprodustat following once-daily administration up to 24 weeks. Data from the 24-week phase II studies were presented at the American Society of Nephrology Kidney Week congress in Chicago, IL, earlier in November.
Anemia is the term used to describe a decrease in normal levels of red blood cells. It is assessed by a patient’s level of hemoglobin, the component of red blood cells that transports oxygen throughout the body. Anemia commonly arises in patients with kidney dysfunction because the kidneys no longer produce sufficient amounts of erythropoietin, a hormone which stimulates red blood cell production. Patients with chronic kidney disease or kidney failure often experience varying degrees of anemia as their disease progresses. This limits oxygen delivery to tissues, contributing to symptoms such as weakness and fatigue.
Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. Prolyl hydroxylase inhibition promotes the production of red blood cells that carry oxygen to where it is needed, similar to the effects that occur in the body at high altitude. Daprodustat is not approved as a treatment for anemia or any other indication anywhere in the world.
(Source: GlaxoSmithKline plc)
Filed Under: Drug Discovery