First Patient Enrolled in TAURUS Patient Preference Study
Posters 795PD, 796PD and 892TiP
CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)--Oct. 1, 2012--
AVEO Oncology (NASDAQ: AVEO) and Astellas Pharma Inc. (TSE: 4503) today
announced new data from the Phase 3 TIVO-1 trial (TIvozanib
Versus sOrafenib
in 1st line advanced RCC)
demonstrating the safety and tolerability profile of tivozanib versus
sorafenib in the first line setting for patients with metastatic renal
cell carcinoma (RCC). Results presented at the ESMO 2012 Congress
(European Society for Medical Oncology) in Vienna, Austria show that
patients treated with tivozanib experienced fewer Grade 3 and off-target
adverse events (AEs), stayed on treatment longer, and required fewer
dose reductions and interruptions compared with those treated with
sorafenib.1 Also presented were the first tivozanib biomarker
data in RCC, and the design of the TAURUS (TivozAnib
Use veRsUs
Sunitinib in advanced renal cell carcinoma)
patient preference study, in which the first patient has now been
enrolled. AVEO recently submitted a New Drug Application to the U.S.
Food and Drug Administration seeking approval for tivozanib.
“Minimizing toxicities associated with anti-VEGF therapy is a vital
consideration in RCC. Adverse events have been shown to contribute to
dose reductions, interruptions and discontinuations of anti-VEGF
therapy,” said Timothy Eisen, Ph.D., FRCP, study investigator, Cambridge
University Health Partners. “The data from TIVO-1 show that treatment
with tivozanib led to fewer side effects and lower rates of dose
modifications than with sorafenib. This suggests that it is easier to
maintain full dose therapy with tivozanib.”
The TIVO-1 global, randomized Phase 3 clinical trial compared the safety
and tolerability of tivozanib and sorafenib in 517 patients with
advanced RCC. Results of the trial were presented at the ASCO Annual
Meeting earlier this year and showed that tivozanib demonstrated a
statistically significant improvement in progression-free survival (PFS)
compared with sorafenib in the overall patient population (median PFS
11.9 months versus 9.1 months; p=0.042, HR=0.797). Further, in a
pre-specified subset of RCC patients who were treatment-naïve, tivozanib
demonstrated a statistically significant improvement in PFS with a
median of 12.7 months compared with 9.1 months for sorafenib (p=0.037;
HR=0.75), making tivozanib the first treatment to demonstrate a median
PFS of greater than one year in this patient population.2
Tivozanib is an investigational drug being evaluated for first-line
treatment of advanced RCC.
Title: Detailed Comparison of the Safety of Tivozanib Versus Sorafenib
in Patients with Advanced/Metastatic Renal Cell Carcinoma (mRCC) from a
Phase 3 Trial
Date/Poster/Location: Oct. 1, 1:00-2:00pm CET /
7:00-8:00am ET; Poster #795PD; Hall F2
Investigators evaluated drug-related AEs versus sorafenib with the goal
of better understanding the tivozanib safety profile. The results of the
safety analysis showed:
-
Investigator-reported adverse events for tivozanib showed lower rates
of dose reductions, interruptions, and discontinuations compared to
sorafenib: dose reductions (11.6% vs. 42.8%, p<0.001), interruptions
(17.8% vs. 35.4%, p<0.001), and discontinuations (4.2% vs. 5.4%)1
-
Drug-related AEs occurred in fewer patients on tivozanib than patients
on sorafenib (67.6% vs. 83.3%)1
-
Fewer patients in the tivozanib group had ≥Grade 3 drug-related AEs
than patients in the sorafenib group (36.3% vs. 51.0%, respectively).1
≥Grade 3 hypertension, an established on-target effect of
angiogenesis inhibitors, was more common in the tivozanib group (23.6%
vs. 15.2%), and ≥Grade 3 hand-foot syndrome (1.9% vs. 16.7%), diarrhea
(1.9% vs. 5.8%) and lipase elevation (0.8% vs. 5.8%) were more common
in the sorafenib group.1
“Our tivozanib development program in RCC is comprehensive and ongoing.
With positive safety and efficacy data from TIVO-1 in-hand, we continue
to explore the role of biomarkers and patient preference with the
ultimate goal of helping clinicians optimize RCC treatment,” said
William Slichenmyer, M.D., Sc.M., chief medical officer at AVEO.
“Additional analyses from our ongoing biomarker program will be
presented at future congresses and our TAURUS patient preference study
vs. Sutent® (sunitinib) is now underway.”
In addition to detailed safety results, pharmacokinetic/pharmacodynamic
data from TIVO-1 were also presented.3
Title: Tivozanib Pharmacokinetic/Pharmacodynamic Analysis of Blood
Pressure and Soluble Vascular Endothelial Growth Factor Receptor 2
(sVEGFR2) in Patients with Advanced Renal Cell Carcinoma
Date/Poster/Location:
Oct. 1, 1:00-2:00pm CET / 7:00-8:00am ET; Poster #796PD; Hall F2
Analyses were conducted using pooled data from patients in AVEO’s
randomized placebo-controlled Phase 2 study of tivozanib in RCC and from
the TIVO-1 study to explore the relationship between tivozanib exposure,
blood pressure and sVEGFR2.3
Patients in the analysis showed a median increase in diastolic blood
pressure of 5mm Hg compared with baseline, and also experienced a
decrease in sVEGFR2 corresponding to tivozanib exposure.3
Hypertension and sVEGFR are known to be on-target biomarkers of activity
and clinical outcome.4,5,6
“One of our goals in becoming a global Category Leader in oncology is to
develop precision medicines that revolutionize the methods used to treat
patients with cancer,” said Stephen Eck, M.D., Ph.D., Vice President of
Medical Oncology, Astellas Pharma Global Development. “We believe the
data showing the combination of tivozanib’s statistically significant
PFS and its tolerability profile represents a potentially important
advancement in the treatment of this disease.”
Title: Patient Preference for Tivozanib Hydrochloride or Sunitinib in
the Treatment of Metastatic Renal Cell Carcinoma (mRCC): TAURUS study
Date/Poster/Location:
Sep. 29, 1:00-2:00pm CET / 7:00-8:00am ET; Poster #892TiP; Hall XL
A review of the clinical study design of TAURUS, a randomized (1:1),
double-blind, crossover controlled, multi-center Phase 2 study comparing
tivozanib versus sunitinib in approximately 160 patients with advanced
RCC who have received no prior systemic therapy was presented at the
meeting. The primary objective of the study is to compare patient
preference for tivozanib or sunitinib.
The first patient has been enrolled in TAURUS, and the study will
continue to enroll patients at sites throughout the United States and
Western Europe.
About Kidney Cancer
Advanced RCC, or kidney cancer, is the ninth most commonly diagnosed
cancer in men and women in the U.S.8 Worldwide it is
estimated that more than 250,000 people are diagnosed and more than
100,000 people die from the disease each year.9 RCC accounts
for more than 90 percent of all kidney cancers.10 Currently
available therapies provide less than one year of median PFS in
treatment naïve patients and are associated with significant toxicities.11
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.12
About Tivozanib
Tivozanib is the first investigational compound to demonstrate a
combination of statistically significant PFS and tolerability in a
pivotal study for advanced RCC versus an approved targeted agent,
sorafenib. Tivozanib is a potent, selective and 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, potentially resulting in improved efficacy and minimal dose
modifications. Tivozanib is an oral, once-daily, investigational
tyrosine kinase inhibitor (TKI) for which positive results from a Phase
3 clinical study in advanced RCC have been reported, and is being
evaluated in other tumors.
About TIVO-1
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 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.1
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 the AVEO/Astellas Collaboration
In February 2011, AVEO and Astellas entered into a worldwide agreement
to develop and commercialize tivozanib outside of Asia for the treatment
of a broad range of cancers. Tivozanib, AVEO's lead investigational
drug, 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. Subject
to regulatory approval, AVEO will lead commercialization of tivozanib in
North America and Astellas will lead commercialization of tivozanib in
the European Union (EU).
About Astellas
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 17,000 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.
About AVEO
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 PlatformTM
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
at www.aveooncology.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements 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: tivozanib’s potential and role in treating
patients with kidney cancer, including the potential that tivozanib may
offer an important advancement in the
treatment of RCC; the potential that few side effects and lower rates of
dose modifications may lead to more optimal dosing of tivozanib;
using biomarkers to help clinicians optimize treatment of kidney cancer;
developing medicines that revolutionize the methods used to treat
patients with cancer; plans by AVEO and Astellas to commercialize
tivozanib in North America and the EU, respectively; AVEO’s plans to
present additional data from its biomarker program and clinical trials
in the future; and AVEO’s plans to leverage its Human Response
Platform™. 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 or the TAURUS
clinical study 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 ability 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 ability to obtain and maintain
adequate protection for intellectual property rights relating to its
product candidates and technologies; unplanned operating expenses;
AVEO’s ability 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 Quarterly Report on Form
10-Q 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.
References
1 Eisen T, Sternberg CN et al. Detailed comparison of the
safety of tivozanib hydrochloride versus sorafenib in patients with
advanced/metastatic renal cell carcinoma (mRCC ) from a Phase III trial.
ESMO 2012 Congress (Poster 795PD)
2 Motzer RJ, Eisen T,
et al. Tivozanib versus sorafenib as initial targeted therapy for
patients with advanced renal cell carcinoma: Results from a phase III
randomized, open label, multicenter trial. J Clin Oncol 2012;30
(suppl; abstr 4501)
3 Nosov DA, Motzer RJ, et al.
Tivozanib pharmacokinetic/pharmacodynamic analysis of blood pressure and
soluble vascular endothelial growth factor receptor 2 (sVEGFR2) in
patients with advanced renal cell carcinoma. ESMO 2012 Congress (Poster
796PD)
4 De Primo SE, Bello CL, Smeraglia J et al.
Circulating protein biomarkers of pharmacodynamic activity of sunitinib
in patients with metastatic renal cell carcinoma: modulation of VEGF and
VEGF related proteins. J Transl Med 2007;5:32.
5
Hutson T, Davis ID, Macheils JH et al. Biomarker analysis and final
efficacy and safety results of a phase II renal cell carcinoma trial
with pazopanib (GW786034), a multi-kinase angiogenesis inhibitor. J
Clin Oncol 2008;26:Abstract 5046.
6 Rini BI,
Michaelson D, Rosenberg JE et al. Antitumor activity and biomarker
analysis of sunitinib in patients with bevacizumab-refracory metastatic
renal cell carcinoma. J Clin Oncol 2008;26:3743–3748.
7
Escudier B, Steelman L et al. Patient preference for tivozanib
hydrochloride or sunitinib in the treatment of metastatic renal cell
carcinoma (mRCC): TAURUS study. ESMO 2012 Congress (Poster 892TiP)
8
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 at: www.cdc.gov/uscs.
9
Cancer Research UK. Available at: http://info.cancerresearchuk.org/cancerstats/world/the-global-picture/#Common;
http://publications.cancerresearchuk.org/downloads/Product/cs_pdf_worldwide_2011.pdf
10
American Cancer Society. Available at: http://www.cancer.org/Cancer/KidneyCancer/OverviewGuide/kidney-cancer--adult--renal-cell-carcinoma-overview-what-is-kidney-cancer.
11
Bhargava, P., Robinson, M. Curr Oncol Rep (2011) 13:103–111
12
Ravaud, A. Annals of Oncology 20 (Supplement 1): i7–i12, 2009
Source: AVEO Oncology & Astellas Pharma Inc.
Investors:
AVEO Oncology
Monique
Allaire, 617-299-5810
or
Media:
Astellas
Pharma Inc.
Astellas US LLC
Jenny Kite, 224-205-5405
or
AVEO
AVEO
Oncology
Rob Kloppenburg, 617-930-5595
or
Nucleus
Communications
Jessica Donnelly, 646-361-2854
or
Pure
Communications
Dan Budwick, 973-271-6085
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