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AVEO Pharmaceuticals, Inc. (AVEO)
March 13, 2013 9:00 am ET
David B. Johnston - Chief Financial Officer and Principal Accounting Officer
Christina Zhang - Barclays Capital, Research Division
Christina Zhang - Barclays Capital, Research Division
Previous Statements by AVEO
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David B. Johnston
Thanks. Very happy to be here today. As expected, I'm going to be making forward-looking statements. Please refer to our SEC filings for all the risks and things associated with those.
So, AVEO, this company has been around a while. It's been around about 11 years. We're in Cambridge, Massachusetts. And we are effectively -- our lead product is tivozanib. It was a product that is in sort of the final phase of the regulatory approval for its first indication. We'll talk about that. And it's company that's built on what we call the Human Response Platform which is our -- which supports all of our discovery in clinical development. We have a significant commercial rights for all of our products and we have capital right now that's efficient without any changes to last till the middle of 2014.
Let's talk about the anticipated approval of tivozanib, our lead product. When you look at the FDA guidelines, what's needed for approval of a new anticancer drug? The first is a positive outcome and an adequate and well-controlled trial. We had that. Our Phase III placebo TIVO-1 trial shows superiority over sorafenib which is the primary endpoint of PFS, or progression-free survival. In the median PFS and the intent to treat population was 11.9 months for tivozanib, versus 9.1 in sorafenib. But importantly, in the treatment-naïve population, which represents the majority of the patients in the Western world and was about 70% of our patients in this trial, the median PFS was 12.7 months for tivozanib and once again, about 9.1 months for sorafenib. It's also supported by a large randomized discontinuation trial that we had in Phase II which also showed superiority that compared to data [ph] was a placebo. So you can see on these bars here, I guess, representing the median PFSs and just as a comparison or just to show where the rest of the world is, pazopanib in their Phase III study for treatment-naïve patients showed 11.1 months compared -- and in their compares trial where they went head-to-head with sunitinib or Sutent, they showed 8.4 months. In Sutent's or sunitinib's Phase III trial, they showed a median PFS of 11.1 months, and in some other trials, they haven't quite replicated that. They're in the 7 to 9.5 month range. The point here is that the PFS that we've seen with tivozanib is among the longest has been seen in the first-line treatment for renal cell carcinoma.
Second is an acceptable safety profile. There was over 1,000 patients have been treated with tivozanib year-to-date or so far rather. We are showing lower rates than sorafenib for the common adverse events, such as hand-foot syndrome, diarrhea and fatigue. The -- I think the most important side effect, which is treatment emergent is hypertension. You can see all grades were about 44%, and about 25% in grades 3 and 4. Once again, generally treatable and reversible. Once again, hypertension has been shown to be an indicator of activity in VEGF, and it's something that is more and more being associated with favorable outcomes.
But the other ones, the big 3, hand-foot syndrome, which is clearly sorafenib's weakness, their Achilles' heel, we had a very low rate of grade 3/4 by 2%, they had 17%. And the others in diarrhea, we had about 1/3 of the Grade 3/4 as compared to sorafenib, and fatigue were about the same. But in the other treatments, in the other TKIs, you would see much higher rates at fatigue and diarrhea. Sorafenib in those 2 areas is considered relatively benign.
But where the rubber hits the road is dose adjustments and dose modifications. So if you look at this, you see on the dose reductions, we had about 12%, and that was about 1/4 -- between 1/3 and 1/4 of what we saw on the sorafenib arm. And in terms of dose interruptions, we had about 1/2, with about 18% compared to 35%. And in terms of discontinuations totally, we're about the same, at about 4% or 5%. Importantly also, the rate of fatal AEs, those are associated primarily with hypertensive responses are relatively low and consistent with reports from past pivotal RCC trials.
The other thing you need is an established dose and regimen. We've had multiple studies that have been conducted showing the 1.5 milligrams per day repeating -- for 21 days, repeating every 28 days, so effectively 3 weeks on 1 week off is the proper dose here.
And lastly and most importantly for us, you need a favorable risk benefit profile. So if you're here, you probably know that PFS is the accepted registration endpoint for advanced RCC. That's what all the other drugs have been approved on. OS is a secondary endpoint and is often compounded, in fact, it's -- no drug has shown statistical improvement in overall survival even versus a placebo. The only exception would be the mTOR inhibitor TAURUS cell in poor prognosis patients, but none of the VEGF TKIs had.