The surprise resurrection of Aveo Oncology’s renal cancer project tivozanib could see an even more surprising European approval after a positive opinion from the CHMP last week. As well as showing that it is not just the FDA that can approve drugs based on questionable data, the decision sets up tivozanib to join the list of products that have the go-ahead in Europe but not the US (see table below).
Of course, developers of many of these projects still hope to get the FDA green light eventually. But the fact that the bar for approval was lower in Europe in these cases suggests that the continent is moving away from its image as the poor cousin, at least in terms of getting new drugs onto the market. Even so, most products make it past the FDA first with an average head start of seven months.
Aveo is pushing for US approval of tivozanib, which has the trade name Fotivda. However, it first needs a win in the Tivo-3 trial, from which topline data are due in the first quarter of 2018. Even if this succeeds, tivozanib seems unlikely to get onto the US market before 2019.
Moreover, data so far do not bode well for Tivo-3: the previous Tivo-1 trial met its primary progression-free survival endpoint, but found that control-arm patients actually lived longer than those on active treatment. Nevertheless, the CHMP granted a positive opinion. The FDA was obviously not minded to be so lenient.
The decision should be followed by full European approval in around three months, which would trigger a payment of up to $16m from Aveo’s partner Eusa Pharma, a much-needed boost to the $33m Aveo had in the bank at the end of the first quarter. Even so, Aveo is likely to need more cash – or another partner – to get tivozanib across the finish line in the US. Astellas handed back US and EU rights in 2014.
But at least Aveo now has European approval almost in the bag, which would put it in line with the likes of Lilly’s arthritis project Olumiant, which got the European green light in February but was rejected by the FDA in April (Olumiant setback opens the door to rivals, April 18, 2017).
Lilly will hope that this is merely a delay rather than a permanent state of affairs. Olumiant’s 2022 sellside consensus forecast – more than double that of the next-biggest product in the table below – seems to back the delay hypothesis.
|Selected products approved in Europe but not the US|
|Global sales ($m)|
|Product||Company||Europe phase||US status||2016||2022||EU approval date|
|Olumiant||Lilly||Marketed||Phase III||-||1,085||Feb 2017|
|Viviant||Pfizer||Marketed||Phase III||133||489||Apr 2009|
|Raxone||Santhera Pharmaceuticals||Marketed||Phase III||19||473||Sep 2015|
|Galafold||Amicus Therapeutics||Marketed||Phase III||5||464||May 2016|
|Translarna||PTC Therapeutics||Marketed||Filed||81||302||Jul 2014|
|Imvamune||Bavarian Nordic||Marketed||Phase III||124||204||Jul 2013|
|Adenuric||Menarini||Marketed||Phase III||97||127||Apr 2008|
|Deltyba||Otsuka Holdings||Marketed||Phase III||14||117||Apr 2014|
|Teysuno||Otsuka Holdings||Marketed||Phase III||248||105||Mar 2011|
|Fotivda||Aveo Oncology||Filed||Phase III||-||-||N/A|
Many of the remaining projects have already been available in Europe for several years with little progress to show in the US, and some look unlikely ever to get the nod across the pond.
One is PTC Therapeutics’ Duchenne muscular dystrophy project Translarna, which the company filed with the FDA “over protest” after originally being rebuffed. An advisory committee is tentatively scheduled for September 28, but the FDA seems in no mood to grant it approval – however, after the surprise green light for Sarepta’s DMD drug Exondys 51 last year, anything seems possible.
Similarly, Amicus’s Fabry disease candidate Galafold was knocked back by the FDA last year, with the agency asking for a new pivotal trial that does not yet appear to have begun.
Aveo would obviously prefer to avoid this scenario and get tivozanib onto the US market as soon as possible. But with everything hinging on the Tivo-3 readout, this is not a given.