Please can you give a brief introduction to tivozanib?
Tivozanib is an oral, once-daily, investigational tyrosine kinase inhibitor, or TKI, that is being investigated for use in patients with advanced renal cell carcinoma (RCC), or kidney cancer.
While we have final data from our phase 3 trial in advanced RCC, tivozanib is being evaluated across a range of solid tumors.
What is known about the mechanism by which tivozanib works?
Tivozanib is an oral, once-daily, investigational tyrosine kinase inhibitor.
How was tivozanib developed?
Our partner, AVEO Oncology, selected RCC as the first cancer type for tivozanib development based on insights gained from their Human ResponseTM Platform indicating that these tumors are enriched for a signature of VEGF pathway deregulation.
The Human Response™ Platform aims to translate cancer biology insights into therapeutics targeted to specific cancer types where they may demonstrate the most benefit.
Given tivozanib’s mechanism of action, RCC, as well as triple negative breast cancer and colorectal cancer, were considered promising targets.
At Astellas, we have a strong focus on strategic alliances and recognize that relationships with outside organizations allow us to potentially help improve the lives of patients around the world. We share AVEO's vision for oncology drug development and believe strongly in the potential of tivozanib.
What stage of development is tivozanib currently at?
A New Drug Application (NDA), submitted by our partner AVEO Oncology, seeking approval in patients with advanced RCC is currently under review by the FDA.
The NDA includes results of the global Phase 3 TIVO-1 (TIvozanib Versus SOrafenib in 1st line Advanced RCC) trial, a randomized superiority-designed pivotal trial evaluating the efficacy and safety of tivozanib compared to sorafenib, an approved targeted agent, in 517 patients with advanced RCC, as well as data from 16 additional AVEO-sponsored studies involving over 1,000 subjects who received tivozanib.
It is the first superiority pivotal study in first-line advanced RCC in which an investigational agent (tivozanib) is seeking to demonstrate statistically significant PFS superiority versus an approved targeted agent (sorafenib).
In addition, we believe tivozanib may have potential in other tumor types.
How effective is tivozanib?
In TIVO-1, tivozanib was studied to demonstrate a statistically significant improvement in progression-free survival (PFS), the primary endpoint of the study, when compared with sorafenib.
Tivozanib demonstrated a median PFS of greater than one year in patients with RCC who were treatment naïve for metastatic disease (median PFS of 12.7 vs. 9.1 months. p=0.037; HR=0.75).
The final overall survival (OS) analysis from TIVO-1 was recently presented at the American Society of Clinical Oncology 2013 Genitourinary Cancers Symposium (ASCO GU), and showed a median overall survival (OS) of 28.8 months for tivozanib versus a median OS of 29.3 months for sorafenib in advanced RCC patients. No statistical difference between the two arms was observed.
Adverse event data from TIVO-1 shows that patients treated with tivozanib stayed on treatment longer, experienced fewer Grade 3 and off-target adverse events, and required fewer dose reductions and interruptions compared with those treated with sorafenib.
How safe is tivozanib?
In TIVO-1, patients treated with tivozanib experienced fewer Grade 3 and off-target adverse events, stayed on treatment longer, and required fewer dose reductions and interruptions compared with those treated with sorafenib.
Grade 3 hypertension, an established on target effect of angiogenesis inhibitors, was more common in the tivozanib group.
The results from TIVO-1 suggest that it is easier to maintain full dose therapy with tivozanib.
How does tivozanib compare to other drugs that are currently available?
In the head-to-head trial, TIVO-1, tivozanib was studied to demonstrate superior PFS compared to sorafenib, an approved targeted agent.
Data also showed lower rates of dose reductions, interruptions, and discontinuations compared to sorafenib in the TIVO-1 trial.
In the absence of other head-to-head studies, we cannot make comparisons to other available therapies.
What impact do you think tivozanib will have?
We believe tivozanib could be an important option in kidney cancer treatment based on clinical trial results included in the NDA.
How do you think the future of advanced RCC treatments will develop?
Drug developers and clinicians continue to seek treatments that have higher specificity to their targets to improve efficacy and reduce off-target effects.
What are Astellas’ plans for the future?
We are excited to be working with AVEO in our efforts to bring tivozanib to patients. Together, we will be focusing on certain key objectives such as further refining our understanding of tivozanib’s activity in RCC and other tumor types.
Where can readers find more information?
More information about the investigational compound tivozanib is available on our website at: www.Astellas.us.
In addition, key data from the TIVO-1 trial regarding tivozanib’s efficacy and safety are available from presentations made at ASCO, ESMO and ASCO GU in recent months.
Would you like to make any further comments?
Through the development of tivozanib as well as other compounds, Astellas is moving towards its goal of becoming a global category leader in oncology by developing precise medicines that revolutionize the methods used to treat patients with cancer.
About Dr. Stephen Eck
Stephen L. Eck, M.D., Ph.D., Vice President, Global Oncology, Astellas Pharma US, Inc. Global Development, has more than 28 years of experience focused primarily in oncology research.
He is a graduate of Harvard University (Ph.D. Chemistry) and the University of Mississippi School of Medicine.
He is also a Fellow of the American Association for the Advancement of Science in pharmacology.
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