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FDA has issued a complete response letter (CRL) to for Aveo’s investigational agent tivozanib for the treatment of patients with advanced renal cell carcinoma (RCC).
FDA has issued a complete response letter (CRL) for Aveo’s investigational agent tivozanib for the treatment of patients with advanced renal cell carcinoma (RCC).
In the CRL, FDA stated that the post-study treatment data for tivozanib produced inconsistent progression-free survival and overall survival (OS) results, thus making the TIVO-1 results uninterpretable and inconclusive. FDA recommends that the company conduct an additional clinical study to support approval of tivozanib for the treatment of advanced RCC.
In addition, FDA also stated that the proposed dissolution acceptance criterion was not supported by the provided dissolution data, and would need to be updated and resubmitted.
"We are disappointed by the complete response letter however based on the ODAC [Oncologic Drugs Advisory Committee] vote last month, the complete response letter from the FDA was not unexpected,” Rob Kloppenburg, vice president, corporate communications and public affairs of Aveo told Formulary. “We have already undertaken a significant corporate restructuring based in anticipation of this outcome.”
In a June 10 press conference, William Slichenmyer, chief medical officer of Aveo, said: "Focusing then on the OS trend noted in the CRL…in 2 early conversations with FDA during meetings in 2008 and 2009, both prior to initiation of TIVO-1, FDA, and Aveo acknowledged that OS in our pivotal trial would be confounded by the use of subsequent anti-cancer therapies-just as it had been in other RCC pivotal trials. We did not expect that to be an impediment to approval any more than it had been in these earlier trials. As it turned out, the extent of the confounding was flagged as a concern by FDA and was the focus of discussion at our ODAC meeting last month.
“We believe that the confounding of OS in TIVO-1 was due to both the impact of the active comparator and the imbalance in the use of second-line therapies,” Slichenmyer said. “In other words, as we stated at ODAC, we believe that the patients who survived longer on the control arm did so because the majority of patients received 2 drugs in succession instead of a single drug."
Kloppenburg said that Aveo will conserve its existing financial resources by implementing a strategy that is expected to extend its cash flow for at least 2 years “so that we have the opportunity to create value through upcoming inflection points including data read-outs from ongoing clinical trials,” he said.
“We will focus our R&D efforts on areas in oncology where our unique insights derived from our Human Response Platform will allow us to develop targeted agents with the potential to provide meaningful clinical benefit for specific patient populations. In particular, Aveo has decided to focus on the ongoing phase 2 trials of tivozanib in colorectal cancer and triple negative breast cancer.”
In addition, Aveo will continue to develop key pipeline assets including AV-203, currently in phase 1 development in solid tumors, as well as ficlatuzumab which, as was previously announced, will be developed through collaborations. Aveo also has certain pre-clinical assets which it will selectively advance using the company’s proprietary Human Response Platform.