AstraZeneca’s latest product approval sets up a trio of firsts – a first-in-class drug, approved in its first world market and – for the first time – that market is China.
The product in question is FibroGen-partnered roxadustat for anaemia in chronic kidney disease patients on dialysis and, according to an AZ spokesman, “potentially spells a new era where China starts to lead the world in innovations in life sciences.”
China is an important market for the orally-active drug because it has far more CKD patients than the US – some estimates suggest five times as many. It also still has gaps in its medical infrastructure that mean treatment with current injectable drugs such as erythropoiesis-stimulating agents (ESAs) – which typically need refrigeration – can be challenging.
Sean Bohen: approval a big step forward in CKD
Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) and according to AZ’s chief medical officer Sean Bohen is the first oral drug in this class, as well as “a significant step towards achieving our ambition to transform care in a condition where prevalence in China is increasing.”
ESAs directly stimulate red blood cell production but can cause blood clots and other cardiovascular side effects. In contrast, HIF-PH inhibitors stimulate endogenous production of erythropoietin, the protein on which ESAs are based. It is though that mechanism causes lower but more consistent EPO levels in the blood.
Analysts suggest the drug could bring in sales of $2bn or more at peak, with plenty of additional upside (perhaps as much as $4bn to $5bn, according to Leerink) if it has a clean enough safety profile to also get approval for less sick, non-dialysis CKD patients. It has competition in late-stage development however, in the shape of Akebia’s vadadustat and GlaxoSmithKline’s daprodustat which are both in phase 3 trials with data due in 2019 or 2020.
The drug’s Chinese approval comes on the strength of an open-label phase 3 trial in dialysis-dependent CKD patients with anaemia who had been treated previously with ESAs such as Amgen’s Epogen (epoetin alfa) and Aranesp (darbepoetin alfa). Roxadustat was compared to treatment with epoetin alfa over 26 weeks, matching the ESA’s efficacy in achieving a significant increase in haemoglobin levels.
AZ and FibroGen have rights to roxadustat in the US, China and other world markets, while Astellas Pharma will sell the drug in Europe and Japan.
Approval in other markets is dependent on a large series of phase 3 trials that were due to report before the end of this year in both dialysis-dependent and dialysis-independent patients.
Meanwhile, a much-anticipated readout from a safety analysis focusing on major adverse cardiovascular events (MACE) – which could be instrumental in unlocking the non-dialysis category – is due in early 2019.
Read PME’s exclusive from October, China: AstraZeneca’s new engine for growth and innovation