Aveo Oncology’s revelation about FDA concerns around overall survival data on its kidney cancer candidate, tivozanib, adds another negative to this story.
With seven targeted agents already available in the US to treat the disease, there is certainly reason to believe that the regulator will look at this measure more closely than it has with other candidates. As such, a smooth approval pathway for this drug is looking less likely, and Aveo’s chances of making a go of it in the increasingly competitive kidney cancer space are looking slimmer.
Aveo had already disclosed a disparity in the overall survival data from its pivotal Tivo-1 study, which pitted tivozanib against Nexavar in first line renal cell carcinoma patients. Estimated overall survival at one year is 81% among patients in the sorafenib arm and 77% for the tivozanib group, although the data set is not yet complete to give a final read out.
Aveo revealed last week that the FDA has “expressed concern” regarding the trend seen and will be reviewing this aspect of the study.
On progression free survival – the measure by which all other renal cell carcinoma drugs have been approved even in the absence of a confirmative overall survival benefit – tivozanib clearly outperformed Nexavar, with a median of 12.7 month versus 9.1 months.
The company blames the disparity on the fact that many more patients who received Nexavar went on to receive subsequent therapy, 53% of them, which in the main was tivozanib. Only 17% of patients given the Aveo drug first were re-treated.
This could well be skewing the overall survival reading. But the FDA will want to rule out any safety issue that might be causing tivozanib patients to die sooner, even as the drug promotes a longer pause in disease activity.
Aveo has never disclosed any notable safety concerns although further data due at medical conferences in the coming months will be scrutinised. As analysts at Leerink Swann point out, the silver lining may be that the FDA concern has been brought up early, giving the company more opportunity to fully address it.
But Aveo – which has said it expects the disparity to persist when all the data is in - will have remove any doubt in the mind of the regulator that the finding has anything to do with safety and is all about a crossover effect.
That could potentially take time. Aveo has already said the filing is likely to be delayed to the fourth quarter, from the third quarter. And in the meantime, other newer competitors in this space are bedding down.
Aveo and partner Astellas - which shares marketing rights in the EU and US - always had to show something extra with tivozanib, given the competition that already exists in renal cell carcinoma. Pfizer’s axitinib, now branded Inlyta, was the most recent agent to win approval at the end of last year, the fourth tyrosine kinase inhibitor after Sutent, Nexavar and Votrient; tivozanib would make five (Axitinib looks set to join competitive field for targeted kidney agents, December 8, 2011).
All target a unique set of kinases and as such are largely defined by their side effect profiles. Inlyta’s relatively clean tolerability was likely a big factor in its green light from the FDA, alongside comparable efficacy to Nexavar.
The first read out from Aveo’s pivotal Tivo-1 trial disappointed with seemingly comparable efficacy to market leader Sutent, based on historical data for the Pfizer drug (Safety data crucial for Aveo to renew market faith, January 4, 2012). Greater information on the drug’s safety has not created the impression of a distinctly differentiated offering.
After ending the year at $17.20, the company’s stock had sunk to $13.30 prior to last week’s news. Today, the shares were trading at $9.48, a 23-month low.
It is hard to see much of a recovery before Aveo can allay safety concerns, and start to differentiate tivozanib from the pack.
To contact the writer of this story email Amy Brown in London at firstname.lastname@example.org