On 25 June, Astellas Pharma and FibroGen announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) had recommended the approval of Evrenzo (roxadustat) for symptomatic anaemia associated with chronic kidney disease (CKD). Evrenzo is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
GlobalData believes the CHMP’s positive opinion will likely shed more light on Evrenzo’s ability to activate the body’s natural response to reduced levels of oxygen in the blood. This is significant because it can lead to the correction of anaemia with a reduced need for intravenous iron therapies. The novel class is seen as a promising new addition to the treatment of CKD anaemia and, if approved, Evrenzo will be the first oral HIF-PHI to become available in Europe for symptomatic anaemia in adults with CKD. Key opinion leaders (KOLs) have stated that HIF-PHIs would likely replace erythropoiesis-stimulating agents (ESAs) when they are used.
The positive CHMP recommendations are based on eight comprehensive multicentre and randomised Phase III programs, which involved a total of 9,600 patients worldwide. The programmes showed Evrenzo was effective in reaching and maintaining target haemoglobin levels in patients with symptomatic CKD anaemia irrespective of dialysis status and/or prior ESA treatment. Evrenzo’s new mechanism of action and oral formulation may potentially help physicians redefine the management of symptomatic CKD anaemia. KOLs have emphasised that HIF-PHIs should preferably be used in patients who are young, have minimal cardiovascular risk, do not have diabetes or high blood pressure, and are in the early stages of CKD anaemia.
For CKD anaemia, the current standard-of-care ESAs have historically been associated with increased risks of cardiovascular safety events, prompting the US Food and Drug Administration (FDA) to strengthen safety information on ESAs numerous times. In addition, until further clinical trial data solidify superior or non-inferior safety of HIF-PHIs in comparison to marketed therapies, physicians will not substantially change their prescribing patterns. The high price of such therapies compared with ESAs may also prove a problem, restricting reimbursement and affecting uptake in a market with widespread domestic ESA biosimilar uptake.
Roxadustat was approved in China in 2018 and 2019 for dialysis-dependent (DD) and non-dialysis-dependent (NDD) settings in adult patients respectively. In Japan, the drug was approved in 2019 and 2020 for DD and NDD settings respectively. In the US, Evrenzo’s new drug application (NDA) is currently under review by the FDA. The CHMP’s latest opinions will now be reviewed by the European Commission before a final decision is made on Evrenzo’s approval in the EU.