CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)--
AVEO Oncology (NASDAQ:AVEO) and Astellas Pharma Inc. (TSE:4503) today
announced that detailed data from TIVO-1 (Tivozanib
in 1st line Advanced RCC), will
be presented on June 2 in an oral session by the principal investigator,
Robert J. Motzer, M.D., attending physician, genitourinary oncology
service, Memorial Sloan-Kettering Cancer Center, professor of medicine,
Weill Medical College, Cornell University, New York, at the 2012 Annual
Meeting of the American Society of Clinical Oncology (ASCO).
TIVO-1 is the first superiority pivotal study in first-line advanced
renal cell carcinoma (RCC) in which an investigational agent (tivozanib)
has demonstrated statistically significant and clinically meaningful
progression-free survival (PFS) superiority versus an approved targeted
agent (sorafenib) in advanced RCC.
"TIVO-1 is novel in that this Phase 3 clinical study used an approved
targeted comparator drug to evaluate first-line RCC treatment," said Dr.
Motzer. "Patients in the study who had no prior treatment for advanced
kidney cancer and who were given tivozanib met the primary PFS endpoint
and tolerated the drug well."
A total of 517 patients were randomized to tivozanib (N=260) or
sorafenib (N=257). The performance status and other prognostic
indicators of patients enrolled in this study were consistent with other
pivotal trials in first-line advanced RCC.
"Despite recent advances in the treatment of kidney cancer, patients are
in need of new options which are effective and well-tolerated," said
Daniel George, M.D., director, GU Medical Oncology and director,
prostate clinic, Duke University. "The superior PFS and favorable
tolerability demonstrated by tivozanib in TIVO-1 represents an important
potential step forward for patients in the treatment of kidney cancer."
Key data from TIVO-1 to be highlighted include (Abstract # 4501):
Based on independent radiological reviews, tivozanib demonstrated a
statistically significant improvement in PFS with a median PFS of 11.9
months compared to a median PFS of 9.1 months for sorafenib in the
overall (Intent To Treat) study population (HR=0.797, 95% CI
0.639?0.993; P=0.042). Objective response rate (ORR) for tivozanib was
33% compared to 23% for sorafenib (p=0.014). The efficacy advantage of
tivozanib over sorafenib was consistent across subgroups in the study.
In patients who were treatment naïve for advanced RCC (70% of total
study population), tivozanib demonstrated a statistically significant
improvement in PFS with a median PFS of 12.7 months compared to a
median PFS of 9.1 months for sorafenib (HR 0.756, 95% CI 0.580?0.985;
P=0.037). This is the longest median PFS reported to date in treatment
naïve advanced RCC patients in a pivotal study.
In the subpopulation of patients who were pretreated with systemic
therapy including cytokines (30% of total study population),
tivozanib demonstrated an improvement in PFS with a median PFS of
11.9 months compared to a median PFS of 9.1 months for sorafenib.
Study results demonstrated favorable tolerability as evidenced by a
distinctively low rate of dose interruptions and reductions. The most
common adverse event (all grades/?grade 3) for tivozanib was
hypertension (T: 44%/25% vs S: 34%/17%) and for sorafenib was
hand-foot syndrome (T: 13%/2% vs S: 54%/17%). Other adverse events
included diarrhea (T: 22%/2% vs S: 32%/6%), fatigue (T: 18%/5% vs S:
16%/4%), and neutropenia (T: 10%/2% vs S: 9%/2%).
The rate of dose interruptions due to adverse events was 18% for
tivozanib compared to 35% for sorafenib (p<0.001).
The rate of dose reductions was 14% for tivozanib compared to 44%
for sorafenib (p<0.001).
Overall survival (OS) data are not yet mature. In TIVO-1, 53% of
patients randomized to the sorafenib arm of the trial went on to receive
subsequent therapy, nearly all of whom received tivozanib after
sorafenib. Based on an early, interim analysis, 81% of these patients
achieved one year OS. In comparison, only 17% of patients randomized to
tivozanib went on to receive a subsequent therapy, and 77% of these
patients achieved one year OS. Mature data are expected to be presented
"We believe that tivozanib may play a significant role in improving the
treatment of patients with advanced kidney cancer," stated Tuan Ha-Ngoc,
president and CEO of AVEO Oncology. "Together with our partner Astellas,
we look forward to the next steps in our registration process and are
continuing our preparations for the planned commercialization of
"Based on these data, we look forward to advancing tivozanib in kidney
cancer with AVEO," stated Steven Ryder, M.D., president, Astellas Pharma
Global Development. "These data further support Astellas' goal of
leadership in oncology and our commitment to developing a world-class
oncology platform based on innovative, research-driven solutions and
About Renal Cell Carcinoma
Advanced RCC, or kidney cancer, is the ninth most commonly diagnosed
cancer in men and women in the U.S.1 Worldwide it is
estimated that more than 250,000 people are diagnosed and more than
100,000 people die from the disease each year.2 RCC accounts
for more than 90 percent of all kidney cancers.3 Currently
available therapies provide less than one year of median PFS in
treatment naïve patients and are associated with significant toxicities.4
These toxicities not only lead to high rates of dose reductions and
interruptions (potentially compromising efficacy), but also can impact a
patient's quality of daily living.5
Tivozanib is a potent, selective, long half-life inhibitor of all
three vascular endothelial growth factor (VEGF) receptors that is
designed to optimize VEGF blockade while minimizing off-target
toxicities. Tivozanib is an oral, once-daily, investigational tyrosine
kinase inhibitor for which positive results from a Phase 3 clinical
study in advanced renal cell carcinoma have been reported, and is being
evaluated in other tumors.
TIVO-1 is a global, randomized Phase 3 superiority clinical trial
evaluating the efficacy and safety of investigational drug tivozanib
compared to sorafenib in 517 patients with advanced renal cell carcinoma
(RCC). TIVO-1 is the first superiority pivotal study in first-line
advanced RCC that has demonstrated statistically significant and
clinically meaningful PFS superiority versus an approved targeted agent
(sorafenib) in advanced RCC. The TIVO-1 study has demonstrated that a
potent, selective and long-half life inhibitor of all three VEGF
receptors can result in superior efficacy and improved tolerability.
The global, randomized, TIVO-1 superiority study evaluated the efficacy
and safety of tivozanib compared to sorafenib in > 500 patients with
advanced RCC. Eighty-six centers participated in the TIVO-1 study,
including centers in Europe and North America. The primary efficacy
endpoint (PFS) was ascertained for each subject by a central panel of
blinded independent radiologists. Patients randomized to the sorafenib
arm of TIVO-1 were eligible to cross over to tivozanib therapy under a
separate protocol after radiographic confirmation of disease
progression. No crossover protocol was available for patients randomized
to the tivozanib arm.
About AVEO Oncology
AVEO Oncology (NASDAQ:AVEO) is a cancer therapeutics company committed
to discovering, developing and commercializing targeted therapies to
impact patients' lives. AVEO's proprietary Human Response Platform?
provides the company unique insights into cancer biology and is being
leveraged in the discovery and clinical development of its cancer
therapeutics. For more information, please visit the company's website
Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical
company dedicated to improving the health of people around the world
through the provision of innovative and reliable pharmaceuticals.
Astellas has approximately 16,800 employees worldwide. The organization
is committed to becoming a global category leader in Urology, Immunology
(including Transplantation) and Infectious Diseases, Oncology,
Neuroscience and DM Complications and Kidney Diseases. For more
information on Astellas Pharma Inc., please visit the company website at www.astellas.com/en.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements of AVEO that
involve substantial risks and uncertainties. All statements, other than
statements of historical facts, contained in this press release are
forward-looking statements, within the meaning of The Private Securities
Litigation Reform Act of 1995. The words "anticipate," "believe,"
"estimate," "expect," "intend," "may," "plan," "target,"
"potential," "could," "should," "seek," or the negative of these terms
or other similar expressions, are intended to identify forward-looking
statements, although not all forward-looking statements contain these
identifying words. These forward-looking statements include, among
others, statements about: the potential efficacy, safety and
tolerability of tivozanib, tivozanib's potential and role in treating
patients with kidney cancer, and AVEO's plans for advancing the
registration process for tivozanib. Actual results or events could
differ materially from the plans, intentions and expectations disclosed
in the forward-looking statements that AVEO makes due to a number of
important factors, including risks relating to: whether the results of
TIVO-1 are sufficient to obtain marketing approval for tivozanib, which
turns on the ability of AVEO to demonstrate to the satisfaction of the
FDA or comparable foreign regulatory authorities the safety and efficacy
of tivozanib based upon the findings of TIVO-1, including its data with
respect to PFS, the rate of adverse events, OS and other information
that the FDA may determine to be relevant to approvability; AVEO's
inability to demonstrate in subsequent trials any safety and efficacy it
demonstrated in earlier trials of tivozanib; ongoing regulatory
requirements with respect to the approval of tivozanib, including the
risk that FDA or any comparable foreign regulatory agency could require
additional positive clinical trials as the basis for product approval;
AVEO's inability to obtain and maintain adequate protection for
intellectual property rights relating to its product candidates and
technologies; unplanned operating expenses; AVEO's inability to raise
the substantial additional funds required to achieve its goals; adverse
general economic and industry conditions; competitive factors; AVEO's
ability to maintain its collaboration with Astellas; AVEO's and
Astellas' ability to successfully launch and commercialize tivozanib if
and when it may be approved for commercialization; and those risks
discussed in the section titled "Risk Factors" and elsewhere in AVEO's
most recent Annual Report on Form 10-K and in its other filings with the
Securities and Exchange Commission. The forward-looking statements in
this press release represent AVEO's views as of the date of this press
release. AVEO anticipates that subsequent events and developments will
cause its views to change. However, while AVEO may elect to update these
forward-looking statements at some point in the future, it specifically
disclaims any obligation to do so. You should, therefore, not rely on
these forward-looking statements as representing AVEO's views as of any
date subsequent to the date of this press release.
1 U.S. Cancer Statistics Working Group. United States Cancer
Statistics: 1999?2007 Incidence and Mortality Web-based Report. Atlanta:
U.S. Department of Health and Human Services, Centers for Disease
Control and Prevention and National Cancer Institute; 2010. Available
2 Cancer Research UK. Available at: http://info.cancerresearchuk.org/cancerstats/world/the-global-picture/#Common;
3 American Cancer Society. Available at: http://www.cancer.org/Cancer/KidneyCancer/OverviewGuide/kidney-cancer--adult--renal-cell-carcinoma-overview-what-is-kidney-cancer.
4 Bhargava, P., Robinson, M. Curr Oncol Rep (2011) 13:103?111
5 Ravaud, A. Annals of Oncology 20 (Supplement 1): i7?i12,