Astellas files new application for expanded use of roxadustat in Japan

Aims for use in anaemia associated with CKD in non-dialysis patients

Astellas has set its sights on extending the use of roxadustat into Japan, for the treatment of anaemia associated with chronic kidney disease (CKD) in non-dialysis patients. 

Together with partner FibroGen, Astellas has submitted a supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare to gain marketing approval for roxadustat.

AstraZeneca hold the development and commercialisation rights of the drug for the potential treatment of anaemia in the US, China and other markets, while Astellas is collaborating with FibroGen for the development of the drug in Japan, Europe and other territories.

The standard treatment used to treat anaemia in people with chronic kidney failure are erythropoiesis-stimulating agents (ESAs), such as darbepoetin alfa.

ESAs directly stimulate red blood cell production but can cause blood clots and other cardiovascular side effects. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).

In contrast to ESAs, HIF-PIH inhibitors stimulate endogenous production of erythropoietin, the protein on which ESAs are based. It is thought that mechanism causes lower but more consistent EPO levels in the blood.

The sNDA is supported by three studies in more than 500 Japanese patients – the first phase 3 conversion study versus active comparator, darbepoetin alfa, met the primary endpoint of non-inferiority and continued to demonstrate maintenance of haemoglobin levels over time.

The other two studies – one phase 3 and one phase 2 – support the safety and efficacy in patients naive to ESAs.

“The data demonstrates that roxadustat is effective in increasing and maintaining Hb levels within the target range in patients with anaemia associated with CKD who are not on dialysis,” said Bernhardt G Zeiher, chief medical officer at Astellas.

“This submission is an important next step to bringing roxadustat to even more patients with this condition in Japan, and this is particularly pertinent in the non-dialysis setting where many patients’ anemia is currently not treated, or not treated to target,” he added.

The first market to approve roxadustat was China, which was crucial for developer AZ as it has far more CKD patients than in the US – some estimates suggest five times as many – with anaemia a common early complication of CKD.

For Astellas in Japan, the prevalence of CKD has increased significantly over time – it is predicted to become the fifth most common cause of premature death globally by 2040.

Analysts have suggested that the drug could bring in sales of $2bn or more at peak, with plenty of additional upside if it can gain the approval for less sick, non-dialysis CKD patients, as Astellas is now aiming for.