The FDA rejected a new drug application for tivozanib, an inhibitor of vascular endothelial growth factor (VEGF), for the treatment of advanced renal cell carcinoma (RCC).
The FDA rejected a new drug application for tivozanib, an inhibitor of vascular endothelial growth factor (VEGF), for the treatment of advanced renal cell carcinoma (RCC). The FDA recommended an additional clinical trial to address concerns over existing clinical data.
Aveo Pharmaceuticals, which had submitted the new drug application for review, announced the decision in a statement today.
The FDA rejected the application based on the results from the phase III TIVO-1 trial, which demonstrated inconsistent progression-free survival (PFS) and overall survival (OS). The trial also had an imbalance in post-study treatments used, causing the results and efficacy of the drug compared with existing treatments difficult to interpret, and the risk-benefit assessment inconclusive, according to the statement.
In May,a 1-13 vote by the FDA’s Oncologic Drugs Advisory Committee (ODAC)declared that the results from the TIVO-1 trial were insufficient to support the approval of the drug. While the FDA is not required to follow the advice of ODAC, it often does.
In the TIVO-1 trial, patients with advanced RCC were randomized to receive tivozanib or sorafenib. Sorafenib is an approved agent for the treatment of advanced RCC.
Patients with advanced RCC were randomized to receive either 1.5 mg of tivozanib once daily for 3 weeks, followed by 1 week of rest (n = 260), or 400 mg of sorafenib twice daily continuously in a 4-week cycle (n = 257). Patients were either treatment-naïve or had received no more than one prior systemic therapy for metastatic disease, and no patients in the study had received any prior VEGF- or mTOR-targeted therapy.
The results of the study were first presented at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting. According to the results, the median PFS in the tivozanib arm was 11.9 months versus 9.1 months in the sorafenib arm (hazard ratio [HR] = 0.797; 95% CI, 0.639-0.993;P= .042). Among treatment-naïve patients who received tivozanib, the median PFS reported was 12.7 months versus 9.1 months in the sorafenib treatment-naïve arm (HR = 0.756; 95% CI, 0.580-0.985;P= .037).1
At the time of the OS analysis (presented at the 2013 Genitourinary Cancers Symposium in February) mortality rates were 45.4% in the tivozanib arm and 39.3% in the sorafenib group, corresponding to a stratified hazard ratio of 1.245 (95% CI, 0.9541.624;P= .105), in favor of sorafenib. The median OS was 28.8 months in the tivozanib arm and 29.3 months in the sorafenib arm.2
Aveo said that it will holda conference call with investors Tuesdayto discuss both the FDA’s rejection of the new drug application as well as recent layoffs at the company.