“In the letter, the FDA stated that the inconsistent progression-free survival and overall survival results and imbalance in post-study treatments make the TIVO-1 results uninterpretable and inconclusive when making a risk-benefit assessment necessary for drug approval,” Aveo said in a statement.
Rather than approve tivozanib, FDA recommended Aveo conduct another Phase III study, and “also stated that the proposed dissolution acceptance criterion was not supported by the provided dissolution data, and would need to be updated and resubmitted,” Aveo added.
As is typical, FDA abided by the recommendations of its Oncologic Drugs Advisory Committee (ODAC), which on May 1 voted 13–1 to recommend that FDA reject tivozanib for renal cell carcinoma (RCC). Following ODAC’s vote, Astellas Pharma pulled financial support for future trials of tivozanib in RCC, and backed off earlier plans to file an application for marketing authorization in Europe. Aveo responded June 5 by announcing plans to eliminate 140 jobs or 62% of its workforce, and reposition the experimental kidney cancer drug for colorectal and breast cancer.
At the time, Aveo President and CEO Tuan Ha-Ngoc told analysts that the restructuring will save the company $190 million over two years, giving it a cash “runway” of two additional years. Ha-Ngoc also insisted that Astellas remained committed to partnering with Aveo on the BATON Phase II clinical trials of tivozanib in triple negative breast cancer and metastatic colorectal cancer.
ODAC questioned why data from Aveo’s TIVO Phase III clinical trial was heavy with results from Eastern European patients while failing to show a better rate of overall survival than any of five currently approved drugs for RCC. The data showed 88.1% of patients randomized to tivozanib and 88.7% randomized to one of the approved drugs, Nexavar (sorafenib).
Aveo has cited other data from TIVO, which studied 517 patients, showing that tivozanib slowed down progression of the disease—though the trial also showed that patients using Nexavar showed a better overall-survival rate. “Tivozanib has greater delayed toxicity or toxicity not recognized,” FDA posited in a hypothesis during a presentation by Amna Ibrahim, M.D., deputy director in the agency’s Division of Oncology Products, at ODAC’s May 2 meeting.
Aveo said its management will discuss the complete response letter and ODAC concerns during a conference call with analysts tomorrow.