Safety data crucial for Aveo to renew market faith

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Aveo Pharmaceuticals’ dented market capitalisation on the back of positive data for kidney cancer drug tivozanib is as much about the unknowns as it is about the knowns. Tivozanib showed it can compete with the best in the space on efficacy and is likely approvable – what the limited phase III data released yesterday failed to demonstrate is any way for it to significantly differentiate itself from the other drugs in its class that have beaten it to market.

As executives stonewalled on any answers beyond the most basic safety data, including drug-related deaths, much about the kinase inhibitor remains a mystery. Without a home run on efficacy, a superior side effect profile will have to be its distinguishing selling point; thus, detailed safety results being saved for cancer conference Asco in June are keenly awaited.

Good, but good enough?

Patients taking tivozanib in the pivotal 517 patient Tivo-1 trial had a significantly longer time to disease progression compared with those taking Nexavar – 11.9 months vs 9.1 months. Performance was even better in the subgroup of patients not exposed to previous cytokine therapy – 12.9 months versus 9.1 months. Aveo executives were quick to stress the performance in that treatment naïve population, as they are hoping for a label that mentions first-line use.

Positive data might be expected to send share prices upward, especially as tivozanib is Aveo’s most valuable product, with a net present value of $753m that now exceeds its current market capitalisation of $614m. However, in Aveo’s case the data fell short of expectations - investors had been looking for progression free survival in excess of 12 months. Shares fell 20% to $13.83 on the news, an eight-month low.

The disappointment also stems from tivozanib’s failure to show anything more than marginal improvement over the drug most commonly used first line, Pfizer’s Sutent, which extends progression free survival by around 11 months.

Still, it is hardly a death blow. Axitinib’s backing from an FDA advisory panel last month shows that there is room for me-too drugs in renal cell carcinoma; specialists in the field could still welcome another treatment option (Axitinib looks set to join competitive field for targeted kidney agents, December 8, 2011).

Whether tivozanib's position as the eigth targeted agent in the space and fifth VEGF-targeting kinase inhibitor, if axitinib is counted, lives up to the commercial hopes of partner Astellas, which in-licensed it for $125m upfront and up to $1.3bn in milestones, is another question entirely (Astellas taps into tivozanib's potential with billion-dollar deal, February 17, 2011). Thus, much is riding on the Asco data, with a superior side effect profile providing the biggest commercial differentiator for tivozanib.

Unclear

However, in a call with investors, Aveo executives would not be drawn on the safety data other than to state that the phase III findings were consistent with phase II – which included low incidences of off-target effects like diarrhoea, weakness, fatigue, swelling of the mouth and mucous membranes of the digestive tract, along with higher incidences of hypertension and hoarseness related to the drug’s mechanism of action.

Even asked pointedly about the possibility of drug-related deaths or serious cardiovascular events, the management team fell back on the need to keep data confidential for an Asco presentation as a reason to say no more. Thus, even with phase III complete tivozanib’s commercial potential will not be clear until mid-May at the earliest. With no catalysts until then, investors have few reasons to bid up the price and many to sell – with the near-silence on safety probably giving many grounds to worry.

It would not be surprising to see the stock move up again as the crucial Asco data near. However, with a less-than-convincing win on efficacy when stacked up against agents already on the market, and likely no further clarity around its side effect profile before May, many commercial risks still surround tivozanib.

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