The US FDA has declined to approve Aveo Oncology and Astellas’ kidney cancer drug tivozanib, saying the results of a pivotal trial supporting the application were “uninterpretable” and “inconclusive”.
The regulator sent Aveo and Astellas a Complete Response Letter (CRL) indicating that tivozanib’s effects on progression-free survival and overall survival in patients with renal cell carcinoma were inconsistent.
It also says that another clinical trial would need to be carried out on the drug before FDA could consider approval, setting back any possible launch in this indication by up to three years.
It had become abundantly clear in recent weeks that the tivozanib programme in renal cell carcinoma was off track, with an FDA committee voting against approval of the drug in May based on a review of several studies including the TIVO-1 trial, which compared tivozanib to Bayer/ Onyx Pharmaceuticals’ already-marketed Nexavar (sorafenib).
Astellas also said recently it would not proceed with a European filing for the candidate in renal cell carcinoma and had decided not to fund any future trials in this indication, while Aveo announced a major restructuring of its operations last week which included a refocusing of its R&D on tivozanib in colorectal and breast cancer.
The primary issue with the TIVO-1 trial was that the design allowed patients to switch from Nexavar to tivozanib once their disease had progressed, which was criticised by the FDA’s panel for potentially skewing the results. Overall, tivozanib did a little worse than Nexavar in terms of overall survival and a cut in staff numbers by 62 per cent.
In a statement Aveo said the FDA also had issues with dissolution acceptance criteria for the drug which it maintained “was not supported by the provided dissolution data, and would need to be updated and resubmitted”.
Tivozanib remains in a phase II trial in colorectal cancer called BATON-CRC, which is comparing first-line treatment with the drug to Roche’s Avastin (bevacizumab), as well as a phase II study in triple-negative breast cancer. Both of these trials are due to report data in the next 18 months.