STAINES, England & CHICAGO, Ill. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Astellas Pharma Europe Ltd. and AVEO Oncology (NASDAQ: AVEO) confirmed
today that tivozanib, a novel once-daily oral tyrosine kinase inhibitor
(TKI), successfully achieved its primary endpoint and demonstrated a
statistically significant improvement in progression-free survival (PFS)
with 11.9 months compared to a median PFS of 9.1 months for sorafenib in
the overall (Intention to Treat) population (HR=0.797, 95% CI
0.639?0.993; p=0.042).1 Importantly, tivozanib also
demonstrated a favourable safety profile, consistent with prior analyses.1
Detailed safety and efficacy data from the TIVO-1 study (Tivozanib
Versus Sorafenib
in 1st line advanced RCC) are
being presented on 2nd June 2012 at the upcoming Annual Meeting of the
American Society of Clinical Oncology (ASCO) in Chicago, Illinois.
Key data to be presented include:
-
Tivozanib is the first treatment to demonstrate greater than one year
median PFS in treatment naive patients with metastatic RCC
(pre-specified sub-analysis)
-
Treatment with tivozanib resulted in the longest reported median
PFS to date in a pivotal study: 12.7 months compared to a median
PFS of 9.1 months for sorafenib. HR = 0.756, p=0.0371
-
This sub-population was approximately 70% of the total study
population1
-
In patients who were pre-treated with systemic therapy, including
cytokines (30% of the study population), tivozanib demonstrated an
improvement in median PFS of 11.9 months compared with a median
PFS of 9.1 months for sorafenib2
-
The efficacy advantage of tivozanib over sorafenib was consistent
across subgroups in the study (HR = 0.797, p=0.042)1,3
-
The objective response rate (ORR) for tivozanib was 33% compared to
23% for sorafenib (p=0.014)2
-
Tivozanib was generally well-tolerated, demonstrating a combination of
superior efficacy and tolerability along with a lower rate of
dose interruptions and reductions2
-
The most commonly reported side effect (all grades/?grade 3) for
tivozanib was hypertension (T: 44%/25% vs S: 34%/17%), a well
established and manageable on target effect of Vascular
Endothelial Growth Factor Receptor (VEGFR) inhibitors2
-
The most common side effect reported for sorafenib was hand-foot
syndrome (T: 13%/2% vs S: 54%/17%)1
-
Other adverse events (all grades/?grade 3) for tivozanib included
diarrhoea (T: 22%/2% vs S: 32%/6%), fatigue (T: 18%/5% vs S:
16%/4%), and neutropaenia (T: 10%/2% vs S: 9%/2%)1
-
The rate of dose interruptions due to adverse events was 18% for
tivozanib compared to 35% for sorafenib2
-
The rate of dose reductions was 14% for tivozanib compared to 44%
for sorafenib2
TIVO-1 is a global, randomised Phase III superiority clinical trial
evaluating the efficacy and safety of investigational drug tivozanib
compared to the approved treatment sorafenib, in 517 patients with
advanced RCC.1,4 All patients in TIVO-1 had clear cell RCC,
had undergone a prior nephrectomy, and had not previously been treated
with a targeted therapy.4 TIVO-1 is the first ever clinical
study using an active TKI comparator to evaluate first-line RCC
treatment.
"Significant advances in the treatment of RCC have been made in recent
years but that doesn't mean that existing treatments are optimal. There
are still real issues with side effects that severely impact patient
quality of life," said Professor Kurt Miller, Chairman of Urology at the
Benjamin Franklin Medical Center, Charité, Berlin, Germany. "These data
are encouraging as they demonstrate that tivozanib not only provides
significantly better progression-free survival against an active
comparator but also seems to have low rates of the burdensome adverse
events that have such a big impact on patients."
RCC accounts for approximately 90% of all kidney cancers, representing
2-3% of all cancers worldwide.5,6 Across Europe, the
incidence of RCC has doubled in the last 30 years7 and there
are now on average 1,700 new cases of RCC per week8, meaning
that kidney cancer is amongst the top ten most common cancers across
Europe affecting men and women.8 40% of patients will be
diagnosed in the advanced stages when prognosis is extremely poor and
the cancer is known to be difficult to treat.6,9
Tivozanib works by blocking the vascular endothelial growth factor
(VEGF) pathway, which plays a role in the formation of blood vessels
that feed tumours. Tivozanib is a potent and selective inhibitor of all
three VEGF receptors (VEGFRs) and has demonstrated in Phase I studies
the potential to be effectively combined with other treatments in RCC
and in other oncology indications.10
-Ends-
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) accounts for approximately 90% of all kidney
cancers, representing 2-3% of all cancers worldwide.5,6 It is
nearly twice as common in men as in women, mainly in adults aged 50-80
years.11 Cancer cells grow in the lining of the kidney's
tubes, developing into a tumour. If left untreated, the tumour can
spread to neighbouring lymph nodes and eventually to other organs.
Over the last two decades there has been an annual increase of about 2%
in incidence worldwide.5 In Europe, approximately 25% of
cases of kidney cancer are attributable to obesity and 25% of cases in
men are attributable to smoking.12 The estimated overall
five-year survival rate for RCC is 44%, which is reduced to 10% for
metastatic disease.13
The primary objectives of medical intervention for RCC are relief of
physical symptoms and maintenance of function.13 Currently
available therapies provide less than one year of median PFS in
treatment naive patients and are associated with significant toxicities.14,15
These toxicities not only lead to high rates of dose reductions and
interruptions (potentially compromising efficacy), but can also impact a
patient's quality of daily living.16 New therapies are well
positioned to meet these needs and advance the treatment of advanced RCC.15
About tivozanib
Tivozanib is a potent and selective inhibitor of all three vascular
endothelial growth factor (VEGF) receptors that is designed to optimise
VEGF blockade while minimising off-target activities. Tivozanib
is an oral, once-daily, investigational tyrosine kinase inhibitor for
which top-line results from a phase III clinical study in advanced renal
cell carcinoma have been reported,1 and the treatment is
being evaluated in other tumours. Astellas is planning to submit
tivozanib to the European Medicines Agency (EMA) during Q3 in 2012.
About TIVO-1
TIVO-1 is a global, randomised Phase III 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 advanced RCC
that has demonstrated statistically significant PFS superiority versus
an approved targeted agent (sorafenib) in advanced RCC. The TIVO-1 study
has demonstrated that a potent and selective inhibitor of all three VEGF
receptors that can result in superior efficacy and improved tolerability.
Eighty-six centres participated in the TIVO-1 study, including centres
in Europe and North America. The primary efficacy endpoint (PFS) was
ascertained for each subject by a central panel of blinded independent
radiologists. Patients randomised 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 Astellas Pharma Europe Ltd.
Astellas Pharma Europe Ltd., located in the UK, is the European HQ of
Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company
dedicated to improving the health of people around the world through the
provision of innovative and reliable pharmaceuticals. The organisation
is committed to becoming a global company by combining outstanding R&D
and marketing capabilities and continuing to grow in the world
pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21
affiliate offices located across Europe, the Middle East and Africa, an
R&D site and three manufacturing plants. The company employs
approximately 4,200 staff across these regions. For more information
about Astellas Pharma Europe Ltd., please visit www.astellas.eu.
About AVEO
AVEO Pharmaceuticals (NASDAQ: AVEO) is a cancer therapeutics company
committed to discovering, developing and commercialising targeted
therapies to impact patients' lives. AVEO's proprietary Human Response
Platform? provides the company's 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.aveopharma.com.
About the AVEO/Astellas collaboration
In February 2011, AVEO and Astellas entered into a worldwide agreement
outside of Asia to develop and commercialise tivozanib for the treatment
of a broad range of cancers. Tivozanib, AVEO's lead product, is a potent
and selective inhibitor of all three vascular endothelial growth factor
(VEGF) receptors that is designed to optimize VEGF blockade while
minimising off-target activities. Subject to regulatory approval, AVEO
will lead commercialisation of tivozanib in North America and Astellas
will lead commercialisation of tivozanib in the European Union (EU).
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.
References
1 Motzer R., Nosov D, 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. (Abstr 4501) Presented at ASCO, June 2012
2 Data on file (AVEO/Astellas)
3 Data on file (AVEO/Astellas)
4 A study to compare tivozanib (AV-951) to sorafenib in
subjects with advanced renal cell carcinoma (TIVO-1). NCT01030783.
Available online: http://clinicaltrials.gov/ct2/show/NCT01030783?term=tivo&rank=1
[Last accessed April 2012]
5 Ljungberg B, Hanbury DC, Kuczyk MA et al. Guidelines
on renal cell carcinoma. European Association of Urology. April 2010.
Available at: http://www.uroweb.org/gls/pdf/Renal%20Cell%20Carcinoma%202010.pdf
[Last accessed May 2012]
6 Bellmunt J, Current Treatment in Advanced Renal Cell
Carcinoma (RCC): Impact of Targeted Therapies in the Management of RCC, European
Urology Supplements 2007;6:484?491
7 Tsimafeyeu I, Aksel E. Renal Cell Carcinoma in the Russian
Federation in 2008. Malign Tumours 2010; 1:1-4 [38
European countries, as defined by the United Nations]
8 Ferlay J, Parkin D M, E. Steliarova-Foucher. Estimates of
cancer incidence and mortality in Europe in 2008. Eur J Cancer
2010; 46:765-781 [40 European countries]
9 The University of Texas MD Anderson Cancer Center. Kidney
Cancer. Available at http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/kidney-cancer/index.html
[Last accessed May 2012]
10 Kabbinavar F et al, Results from a phase I trial of
tivozanib (AV-951) combined with temsirolimus therapy in patients (pts)
with renal cell carcinoma (RCC). J Clin Oncol 2011;29:(suppl;
abstr 4549)
11 Cancer Research UK. Kidney cancer statistics - UK. http://info.cancerresearchuk.org/cancerstats/types/kidney/index.htm?script=true
[Last accessed May 2012]
12 Lindblad P. Epidemiology of renal cell carcinoma. Scand
J Surg 2004;93(2):88-96
13 National Institute for Health and Clinical Excellence.
Bevacizumab (first-line), sorafenib (first- and second-line), sunitinib
(second-line) and temsirolimus (first-line) for the treatment of
advanced and/or metastatic renal cell carcinoma. Technology appraisal
TA178. London: NICE; August 2009
14 Sutent EPAR discussion. European Medicines Agency, 2006.
15 Bhargava, P, Robinson M. Development of Second-Generation
VEGFR Tyrosine Kinase Inhibitors: Current Status. Curr Oncol Rep
2011;13:103-111
16 Ravaud, A. How to optimise treatment compliance in
metastatic renal cell carcinoma with targeted agents. Annals of
Oncology 2009;20(1):i7-i12
