dm+d

Unassigned

New Medicines

Anaemia in chronic kidney disease in dialysed and non-dialysed patients 

Information

New molecular entity
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Apr 22Filed in US [14].
Mar 22Filed in EU via centralised procedure [14].
Mar 22Filings in EU and US expected imminently [12].
Nov 21GSK plans to file daprodustat with the FDA in H1 2022 [11]
Jun 20GSK confirms at Japanese launch that the ASCEND trial series is intended to support registration submissions worldwide [6].
Aug 19Submitted for licensing in Japan; no indication so far of timing for EU/US licensing [5].

Category

A small molecule prolyl hydroxylase inhibitor
UK prevalence of stage 3-5 CKD is about 8.5% (8,500 per 100,000 people). Prevalence of anaemia in CKD (defined as a haemoglobin level less than 12 g/dL in men and postmenopausal women and less than 11 g/dL in premenopausal women) is about 12% [1].
Anaemia in chronic kidney disease in dialysed and non-dialysed patients 
Oral

Further information

Yes

Trial or other data

Apr 22PIII ASCEND-ID RCT (NCT03029208; n=312) found daprodustat was noninferior to darbepoetin alfa in treating anaemia of CKD in incident dialysis patients (mean haemoglobin concentration 10.5 g/dL vs. 10.6 g/dL, respectively, at study end) [13].
Nov 21PIII RCT (NCT02879305; n=2,964) in patients undergoing dialysis found daprodustat was noninferior to erythropoiesis-stimulating agents for change in haemoglobin level from baseline (difference 0.18g/dL; 95% CI 0.12 to 0.24) and major cardiovascular adverse events (25.2%vs26.7%, respectively; HR 0.93; 95% CI 0.81 to 1.07) [10].
Nov 21PIII RCT (NCT02876835; n=3,872) in patients not undergoing dialysis found daprodustat was noninferior to darbepoetin alfa for change in haemoglobin level from baseline (difference 0.08g/dL; 95% CI, 0.03 to 0.13) and major cardiovascular adverse events (19.5% vs 19.2%, respectively; HR 1.03; 95% CI, 0.89 to 1.19) [9].
Jul 21Following delays to approval of roxadustat, daprodustat has a chance of being first-to-market in US. GSK announced that ASCEND program met all of its main efficacy endpoints and matched the standard-of-care treatment in terms of major adverse cardiovascular events. The company are expected to release further data whilst planning for filings [8].
Nov 20ASCEND-TD completed in June 2020, ASCEND-NHQ in October 2020, ASCEND-D is expected to complete November 2020 and ASCEND-ND in April 2021 [7].
Oct 18Results from a PIII 52-week study of 271 haemodialysis-dependent patients in Japan announced, indicating that oral daprodustat met its primary endpoint of non-inferiority to darbepoetin alfa IV injection, as measured by mean haemoglobin levels over Weeks 40 to 52 [5].
Jan 18ASCEND-TD (NCT03400033) multi-centre RCT initiated to examine the efficacy and safety of oral daprodustat given three times weekly in patients undergoing dialysis compared to epoetin IV. It joins the ASCEND-D (NCT02879305), ASCEND-ND (NCT02876835) and ASCEND-ID (NCT03029208, patients newly initiating dialysis) trials in the series [3].
Nov 16: GSK begins a PIII programme including two studies evaluating daprodustat safety and efficacy compared to recombinant human erythropoietin in dialysis dependent subjects with anaemia associated with CKD (ASCEND-D) and in non-dialysis dependent patients with the condition (ASCEND-ND). The co-primary endpoints for both trials 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) [2].