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Tolerability of Aveo/Astellas Pharma Inc. (YPH.BE) Kidney Cancer Drug Impresses


5/17/2012 6:43:20 AM

STAINES, England & CHICAGO, Ill. & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Astellas Pharma Europe Ltd. and AVEO Oncology (NASDAQ: AVEO - News) 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

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 - News) 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

Contact:

Red Health

Julia Flint

T: 0207 025 6411 / 0777 333 1815

Julia.Flint@redconsultancy.com

or

Astellas Pharma Europe Ltd.

Mindy Dooa

T: 01784 419 400 / 07826 912 339

Mindy.Dooa@astellas.com




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