The FDA has rejected a new drug application for tivozanib for the treatment of advanced renal cell carcinoma, recommending an additional clinical trial to address concerns over existing clinical data.
The FDA has rejected a new drug application for tivozanib for the treatment of advanced renal cell carcinoma (RCC), recommending an additional clinical trial to address concerns over existing clinical data.
Aveo Pharmaceuticals, which had submitted the new drug application for review of the inhibitor of vascular endothelial growth factor (VEGF), announced the decision in a statement today.
The FDA rejected the application in its current form because the results from the phase III TIVO-1 trial showed inconsistent progression-free survival (PFS) and overall survival (OS) results. The trial also had an imbalance in post-study treatments used, making its results and the efficacy of the drug compared with existing treatments difficult to interpret, and the risk-benefit assessment inconclusive, according to the statement.
In May, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 13-1 that the single trial on tivozanib provided insufficient evidence for a decision regarding the drug’s approval. 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, the latter of which is already approved 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 1week 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 last year’s annual meeting of the American Society of Clinical Oncology (ASCO), with follow-up results presented at the organization’s 2013 Genitourinary Cancers Symposium.
According to the results presented at the 2012 ASCO meeting, the median PFS in the tivozanib arm was 11.9 months compared with 9.1 months in the sorafenib arm (hazard ratio [HR] = 0.797; 95% CI, 0.639-0.993; P = .042). A more marked improvement was observed in treatment-naïve patients who received tivozanib, with those patients experiencing a median PFS of 12.7 months compared with 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 Genitourinary Symposium, mortality rates were 45.4% in the tivozanib group and 39.3% in the sorafenib group, corresponding to a stratified hazard ratio of 1.245 (95% CI, 0.954—1.624; P = .105) trending 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 the company will hold a conference call with investors Tuesday to discuss both the FDA’s rejection of the new drug application as well as recent layoffs at the company. Details of the conference call can be found here: goo.gl/tv8ev.