Author: Chris Rees, TenStocks
Covestor model: TenStocks
Disclosure: Long AVEO
There are three legs to getting a new drug approved for renal cell carcinoma (RCC).
1. Efficacy.
2. Safety.
3. Overall survival rate.
For efficacy Tivozanib, or Tivo, from Aveo Pharmaceuticals (AVEO) has racked up the highest progression free survival rate of any drug in RCC with 12.7 months in treatment naïve (first-time) patients. Treatment naïve is important because it offers the cleanest data. Sunitinib, which is marketed as Sutent by Pfizer (PFE) and GlaxoSmithKline’s (GSK) Pazopanib, also known as Votrient, come next at 11.5 and 11.1.
Both these drugs have been approved. For safety Tivo has compelling data. Current RCC meds are a minefield of unwanted side effects. For example, roughly 50% of patients taking current RCC medicines suffer diarrhea versus around 10% for Tivo.
Fatigue is another unwanted adverse event. For Sunitinib it’s around 50%, Pazopanib 20%, Tivo is about 10%. Nausea and vomiting are less with Tivo. Dose reductions and interruptions due to adverse events are lower as well.
Across the board the relative safety profile of Tivo stands out. If you have a drug that’s as good as or better than anything currently on the market with an overall superior safety profile, I think that votes in favor of approval.
For overall survival there is a potential fly in the ointment. The FDA has expressed ‘concern’ over the 77% one-year survival rate of Tivo patients in the phase 3 Tivo-1 trial. The market has suddenly cast doubt on the approvability of Tivo based on this concern. The stock has got hammered. It’s a large position for our Covestor Ten Stocks model and it hurts. The stock has sold off from around $13 to close at $7.97 on August 8th. But is the market reading this right?
First off, the Tivo-1 trial was split into two groups with roughly half getting Tivo and half getting Sorafenib, which is co-marketed as Nexavar by Bayer (BAYRY) and Onyx Pharmaceuticals (ONXX).
Upon progression roughly 50% of the Sorafenib arm switched over to Tivo while less than 20% of the Tivo arm switched upon progression. The overall survival rate for the Sorafenib arm was 81%. It could be argued the longer OS in this arm was mainly or totally due to it being a Sorafenib+Tivo arm. But I’m not sure that’s the point.
I’ve looked at data of other RCC meds for one year overall survival. The average comes in at 80%. The best is 81%, and the worst is Tivo at 77%. Pfizer’s Axitinib (trade name: Inlyta) was approved with 79%. There were 260 patients in the Tivo arm. That’s a small sample on a notoriously unreliable data point. The 77% seems well within the margin of error.
It’s difficult to measure drug specific overall survival rate with any accuracy especially where crossover medications have been used. That’s why the FDA has approved RCC drugs on the basis of Progression Free Survival (PFS). It’s a more measurable proxy for overall survival.
I think it’s possible the FDA is signaling it would like to see some positive movement in OS on future RCC drug applications despite the unreliability of the data. The market currently thinks the FDA will not approve Tivozanib. My work suggests something different.
