After FDA snub, EMA backs FibroGen, Astellas' roxadustat

The EU regulator has approved FibroGen and Astellas Evrenzo for adults with anaemia caused by chronic kidney disease (CKD), just days after the FDA turned down the drug in the US.

The decision makes Evrenzo (roxadustat) the first oral HIF-PH inhibitor to be cleared for use in the EU, ahead of rival candidates daprodustat from GlaxoSmithKline and Akebia Therapeutics' vadadustat.

It has been cleared for use in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients, providing an oral alternative to injectable erythropoiesis-stimulating agents (ESAs).

The green light was expected after the EMA's CHMP scientific committee in June, which issued a positive opinion on Evrenzo based on phase 3 trial results which showed the drug helped people with CKD anaemia hit target haemoglobin levels, regardless of dialysis status and prior ESA treatment.

Earlier this month, the FDA said it wanted to see another clinical trial of roxadustat before it will consider approval of the drug, acting on the advice of its advisory committee that voted 13 to one against approval of the drug at a meeting last month.

The US regulator said that the drug's efficacy was not in question, but it had concerns about its safety – mainly with relation to the risk of serious thromboembolic events.

The decision was a big blow to NDD patients with CKD in the US, as the current injectable ESAs are not used to treat anaemia in this group because of a risk of clotting side effects.

Approval in the NDD group had been behind blockbuster sales predictions for roxadustat ahead of the FDA rejection, which looks set to delay approval in the US – where the drug is partnered with AstraZeneca – by several months at least.

FibroGen has said it will carry out a 10,000 patient post-marketing study to see whether a lower dose of roxadustat would mitigate the risk of thrombosis and maintain the benefits on reducing anaemia in CKD, but the FDA was not swayed by the plan.

The EU approval triggers a of $120 million milestone payment from Astellas to FibroGen, which will also receive royalties based upon European net sales. Astellas also has rights to the drug in Japan – where it also approved and on sale – as well as Turkey, Russia, the Middle East, and South Africa.

In the US, roxadustat's delay has provided an opportunity for GSK and Akebia to beat FibroGen and AZ to market. Akebia has filed for FDA approval of vadadustat with a decision due by 29 March next year, while GSK claimed its first approval for daprodustat under the Duvroq brand name in Japan in June.

GSK is waiting on the results of two more phase 3 trials later this year before moving ahead with regulatory filings in the US and Europe.