Aveo Oncology and Astellas Pharma said today they will end their three-year collaboration to codevelop tivozanib (ASP4130) after the Japanese drug developer exercised its option to terminate the partnership based on disappointing clinical status in the three indications for which the cancer treatment was studied.
The companies also agreed to end their ongoing Phase II Biomarker Assessment of Tivozanib in Oncology (BATON) study in patients with colorectal cancer (CRC) effective August 11—when tivozanib rights will be returned to Aveo. The companies agreed to share committed development expenses equally, including the costs of winding down discontinued tivozanib clinical development programs.
Tivozanib is an oral tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3. Aveo won $125 million upfront and stood to gain $1.3 billion in potential milestone payments from Astellas when the companies launched their collaboration in February 2011. The companies envisioned developing tivozanib for a variety of cancer indications and marketing the drug outside Asia.
“We are realigning our resources behind key development opportunities to bring clinically meaningful treatments to patients and create shareholder value,” Aveo President and CEO Tuan Ha-Ngoc said in a statement. “We look forward to outlining our corporate strategy when we report our fourth-quarter and full- year 2013 results.”
Aveo has not confirmed a date for release of those results, which had been expected this week.
The termination and return of rights will cap more than a year of disappointments for tivozanib and its codevelopers. BATON had been headed for failure as early as December, when Aveo conceded that the Phase II trial was “unlikely to meet the primary endpoint” of superiority with modified FOLFOX6 compared to bevacizumab with modified FOLFOX6 as first-line treatment in patients with advanced metastatic CRC.
CRC was one of the three indications for which tivozanib struggled to win approvals. Just last month, the companies halted the BATON-BC Phase II study of the drug for triple-negative breast cancer, citing an insufficient number of patients enrolled. BATON-BC was designed to evaluate tivozanib’s efficacy with paclitaxel compared to placebo with paclitaxel in patients with locally recurrent or metastatic triple-negative breast cancer who have received no more than one systemic therapy for advanced or metastatic breast cancer.
The worst setbacks for tivozanib and its co-developers came in June, when the the FDA rejected the companies’ application to market the drug. Instead, the agency issued a Complete Response Letter that faulted as uninterpretable and inconclusive Aveo’s results from its Tivozanib Versus sOrafenib in 1st Line Advanced RCC (TIVO-1) trial of tivozanib for renal cell carcinoma (RCC) and requested a new trial.
The FDA’s decision echoed the advice of its Oncologic Drugs Advisory Committee (ODAC), which on May 1 voted 13–1 to recommend that the FDA reject tivozanib for RCC. ODAC questioned why data from TIVO-1 was heavy with results from Eastern European patients while failing to show a better rate of overall survival than sorafenib (marketed by Bayer HealthCare as Nexavar®) or any of four other currently approved drugs for 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 to the committee action June 5 by announcing plans to eliminate 140 jobs, or 62% of its workforce, and to reposition the experimental kidney cancer drug for CRC and breast cancer.
“We remain committed to the field of oncology to help meet the unmet needs of cancer patients,” said Yoshihiko Hatanaka, Astellas’ president and CEO.