Cancer, EMA, FDA, Regulatory

After falling short on prelim OS data, EMA tells Aveo it wants to see something better on its long suffering tivo this summer — or else

When Aveo Oncology scored European approval in 2017 for its lead cancer drug tivozanib — despite the treatment’s chequered past — a comeback story was in the making. New pivotal data could now threaten that approval, and the company’s investors are losing patience.

In 2013, data from the 517-patient TIVO-1 study testing tivozanib against sorafenib in frontline patients with advanced renal cell carcinoma (RCC) showed patients given the Aveo drug did not live as long as those on sorafenib (median OS of 28.8 months for tivozanib versus 29.3 months for sorafenib) — although the difference in overall survival was not statistically significant (HR=1.245, p=0.105). However, tivozanib did meet the main goal of significantly improving progression-free survival (PFS) by a median of 2.8 months (HR=0.797; P=0.042).

The FDA was not impressed. The agency’s cancer czar Richard Pazdur issued a scathing review of tivozanib, asserting that an approval for a drug that could be tied to an increased risk of death would set a dangerous precedent. An outright rejection followed.

Michael Bailey

In 2016, Aveo’s fresh faced management agreed to fork over $4 million to settle SEC charges that were imposed on the drug developer’s former top executive team — which stepped down the preceding year — for keeping secret the FDA’s demand for a new tivozanib study, to answer lingering concerns over patient deaths in TIVO-1, in order to qualify for approval.

Meanwhile, the EMA was a little more generous. In 2017, the EU sanctioned Aveo’s partner EUSA Pharma approval for tivozanib — but with a caveat that topline data results from the 351-patient TIVO-3 trial — evaluating tivozanib against sorafenib in RCC who have failed at least two prior regimens — would be provided as part of post-marketing requirements.

Much like TIVO-1, data from TIVO-3 unveiled last November showed tivozanib induced a statistically significant improvement in PFS (Median PFS was 5.6 months for tivozanib compared to 3.9 months for sorafenib; HR=0.74; p=0.02). Months later, Aveo provided preliminary OS data that suggested a non-statistically significant difference in OS favoring sorafenib (HR=1.12, p=0.44).

On Wednesday, Aveo in a filing said the EMA has asked for the additional interim OS analysis of TIVO-3 by August 2019, and that “regulatory action” will be considered if a negative OS trend is confirmed. In effect, if this OS trend is cemented with mature data by August, Aveo could see its EU approval rescinded.

The Cambridge, Massachusetts-based biotech’s shares $AVEO tumbled nearly 23% to $1.22 before the bell.


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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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