The FDA has rejected the oral VEGF receptor tyrosine kinase inhibitor tivozanib, intended for the treatment of renal cell carcinoma, according to the drug's developer.
AVEO Oncology, of Cambridge, Mass., said it has received a Complete Response letter from the agency, saying the drug will not be approved based on the current new drug application.
The ruling is not a surprise -- in May, an FDA advisory committee voted 13-1 that the drug should not be approved.
The company said the FDA's letter cited inconsistent progression-free and overall survival results, as well as imbalance in post-study treatments.
Because of those findings, the agency letter said, the results -- from a single study -- are "uninterpretable and inconclusive when making a risk-benefit assessment necessary for drug approval."
The agency suggested the company conduct a new clinical trial to support approval.
In a single randomized but unblinded trial of 517 patients, tivozanib delivered progression-free survival of 11.9 months, compared with 9.1 months from treatment with sorafenib (Nexavar), the advisory panel was told. The improvement was significant at P=0.04.
But after 2 or more years of follow-up, overall survival in the tivozanib arm was 28.8 months, compared with 29.3 months for sorafenib, a difference that yielded a nonsignificant hazard ratio of 1.25 (with a 95% confidence interval from 0.95-1.62).
Panel members found it difficult to reconcile the two outcomes.
"I cannot picture how I would be able to talk with a patient about treating him or her with a drug, tivozanib, that would allow that person to live without progression longer but to possibly die faster than if I treated that person with another available renal cell carcinoma drug," commented committee Chair Mikkael Sekeres, MD, of the Cleveland Clinic's Taussig Cancer Institute.