Aveo comeback highlights a transatlantic split

After the recent EU positive opinion for Aveo's tivozanib, EP Vantage takes a look at other projects approved in the EU, but not the US.

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The surprise resurrection of Aveo Oncology’s renal cancer project tivozanib could see an even more surprising EU 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, the 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 also pushing for US approval of tivozanib, which has the trade name of Fotvida. However, it first needs a win in the Tivo-3 trial, from which top-line data are due in the first quarter of 2018. Even if it succeeds, tivozanib seems unlikely to get onto the US market before 2019.

The 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. Nonetheless, this was enough for the CHMP to grant its 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 $33.4m it had in the bank at the end of the first quarter. Even so, Aveo is likely to need more cash – or a partner – to get tivozanib across the finish line in the US.

But at least Aveo now has European approval almost in the bag, which would put it in line with the likes of Eli Lilly’s arthritis project Olumiant. The latter 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

       

Annual WW sales ($m)

 

Product

Company

Europe phase

USA phase

2016

2022

EU approval date

Olumiant

Eli 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

Source: EvaluatePharma.

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 to ever 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.

Trial

Setting

ID

Tivo-1

1L RCC

NCT01030783

Tivo-3

3L RCC

NCT02627963

To contact the writer of this story email Madeleine Armstrong or Edwin Elmhirst in London at news@epvantage.com or follow @ByMadeleineA or @EdwinElmhirst on Twitter

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