GlaxoSmithKline has started a phase III development programme investigating daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), as a treatment for anaemia associated with chronic kidney disease (CKD).
GlaxoSmithKline explained in its press release issued on Thursday that the phase III programme includes two studies evaluating the safety and efficacy of daprodustat compared to recombinant human erythropoietin:
- ASCEND-D (Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis) will enrol approximately 3,000 dialysis dependent subjects with anaemia associated with CKD switching from an erythropoietin-stimulating agent (ESA).
- ASCEND-ND (Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis) will enrol approximately 4,500 non-dialysis dependent subjects with anaemia 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 haemoglobin 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 programme, said: “For many patients with chronic kidney disease, treating their anaemia 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 programme is based upon data from phase II clinical trials that were designed to characterise the dose-response relationship between daprodustat and haemoglobin 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, Illinois, earlier in November.