Akebia’s vadadustat knockback increases class doubts

 Vifor’s recent doubling down on Akebia’s anaemia pill vadadustat looks like a bad move after yesterday’s US complete response letter. The partners’ new agreement, in February, had been greeted as a welcome sign of Vifor’s confidence in Akebia’s ability to get the asset over the finish line, despite long-standing toxicity worries. But these concerns have come back to haunt Akebia, with the FDA yesterday citing issues including an increased risk of thromboembolic events and liver injury. The agency has called for new clinical trials, but it is hard to see how vadadustat will come back from this – a fact reflected in the 66% fall in Akebia’s share price yesterday. The surprise among investors is surprising itself, given the recent history of this drug class, the HIF-PH inhibitors. Last August the FDA also rejected Astrazeneca and Fibrogen’s roxadustat after an adcom revealed toxicity issues with that project. Still, ever-optimistic sellside analysts had given vadadustat a 50/50 chance of approval. Glaxosmithkline’s daprodustat is now the foremost HIF-PH contender, and that company will have to hope that pivotal results are as clean as they seem.

The HIF-PH inhibitor pipeline
Product	Company	Status
Evrenzo (roxadustat)	Astrazeneca/Fibrogen/Astellas	Approved in Japan and Europe; US CRL Aug 2021
Vadadustat	Akebia Therapeutics/Vifor	Approved in Japan, US CRL Mar 2022
Duvroq (daprodustat)	Glaxosmithkline	Ph3 hit Nov 2021
Source: Evaluate Pharma. https://www.evaluate.com/vantage/articles/news/policy-and-regulation-snippets/akebias-vadadustat-knockback-increases-class