GSK begins phase 3 trials of kidney drug

GlaxoSmithKline has begun late stage development of its daprodustat, for anaemia associated with chronic kidney disease.

GSK said the phase 3 programme included two studies evaluating the safety and efficacy of daprodustat, compared with recombinant human erythropoietin.

Daprodustat is one of a group of around 20 new drugs that GSK aims to file before 2020, which it hopes could boost sales by at least £6 billion.

The drug offers a new oral alternative to the standard treatment, Amgen's Epogen (epoetin alfa) and Aranesp (darbepoetin alfa). These injectable drugs became blockbusters in the 1990s and 2000s, but concerns about their cardiovascular safety has seen their use pared back.

Julian Jenkins, GSK, 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 3 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.”

There will be two studies in the phase 3 programme – ASCEND-D will enrol around 3,000 dialysis dependent patients with anaemia associated with CKD switching from an erythropoietin-stimulating agent (ESA).

The second study ASCEND-ND will enrol around 4,500 non-dialysis dependent subjects with anaemia associated with CKD, and will include patients either switching from or naïve to ESA.

For both studies, co-primary endpoints are time to first occurrence of major cardiovascular events and mean change in haemoglobin between the baseline and efficacy period (mean over weeks 28-52).

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.

Design of the phase 3 programme is based upon data from phase I2 clinical trials that were designed to characterise the dose-response relationship between daprodustat and haemoglobin at four weeks and assess the safety and tolerability of daprodustat following once-daily administration up to 24 weeks.

Data from the 24-week phase 2 studies were presented at the American Society of Nephrology Kidney Week congress in Chicago earlier in November.