GSK’s Pazopanib significantly delayed tumor progression in patients with advanced kidney cancer

Issued: Monday 1^st June 2009, London, UK and Philadelphia, PA

— Today, GlaxoSmithKline announced the results of a Phase III study demonstrating that pazopanib reduced the risk of tumor progression or death by 54 percent compared to placebo.¹

Study findings demonstrated that the median time without tumor growth or death (progression free survival or PFS) in the pazopanib treated group was 9.2 months compared to 4.2 months in the placebo group.  When specific patient groups were evaluated, those with no prior drug treatment experienced 11.1 months of median PFS with pazopanib versus 2.8 months with placebo.¹ Patients who had previously received cytokine-based treatment showed 7.4 months of median PFS with pazopanib versus 4.2 months with placebo.¹ These results were featured in an oral presentation at the annual American Society for Clinical Oncology (ASCO) meeting in Orlando, Florida.²

“The study shows that pazopanib significantly improved PFS for patients regardless of whether or not they had prior therapy. While there have been many treatment advances for patients with advanced kidney cancer, there is still a need for medicines that are effective and well-tolerated,”said Dr. Cora N. Sternberg, Department of Medical Oncology, San Camillo and ForlaniniHospitals, Rome, Italy. “Additionally, patients did not experience a significant decline in health-related quality of life with no significant differences between pazopanib and placebo.”

The results are based on a global, double-blind, Phase III trial of 435 patients with advanced kidney cancer (renal cell carcinoma) who had either received no prior drug treatment or had received prior cytokine-based treatment.¹ Patients were randomly assigned on a 2-to-1 basis to receive either pazopanib or placebo.¹  Pazopanib reduced the risk of disease progression or death by 54% (hazard ratio = 0.46 with 95% confidence interval 0.34 to 0.62; P<>¹ The overall response rate in the pazopanib arm for the overall study population was 30% with duration of response of 59 weeks.¹

The majority of adverse events were mild to moderate, the most common (incidence =20%) being diarrhea, hypertension, hair color change, nausea, anorexia, and vomiting.  The most common grade 3/4 adverse events (incidence >3%) were diarrhea (4%), hypertension (4%), and asthenia (3%). The most common laboratory abnormalities (incidence =50%) were elevated levels of liver enzymes known as transaminase, with elevated ALT as the most common grade 3/4 event (12%).¹ Investigator-reported serious adverse events included liver-related events (3%), arterial thrombotic events (3%) and hemorrhage (3%).⁴In this study, approximately 4% of patients on treatment compared to 3% of patients on placebo had a fatal event.  Investigators attributed death due to study drug in approximately 1.4% of patients in the treatment arm.¹ Some of these adverse events/serious adverse events have been reported with this class of agents.⁵

Pazopanib is an oral medicine that prevents the growth of new blood vessels to tumors.⁶ The growth of new blood vessels is a process called angiogenesis.⁷ All solid tumors need blood vessels to survive, and by stopping or slowing this process, medicines in this category may halt the progression of tumor growth.⁷

In December 2008, GSK submitted a GSK new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and, in early 2009, a European marketing authorization application (MAA) to the European Medicines Agency (EMEA) for pazopanib for the treatment of advanced renal cell carcinoma (RCC) based on these data. The submission was recently accepted by the FDA. Pazopanib is not yet approved in any country for any indication at this time.

“We’re extremely pleased to see the progress in developing pazopanib for advanced kidney cancer, but this represents just one type of cancer in need of new treatments. Our global studies using pazopanib are designed to find new ways to use a proven mechanism to fight a diverse group of cancers,” said Paolo Paoletti, Senior Vice President, R&D Oncology Unit. “This further demonstrates our efforts to discover new medicines that provide tangible clinical benefits for patients.”

About RCC

Renal cell carcinoma (RCC) is the most common type of kidney cancer and accounts for approximately nine out of ten cases.⁸ In 2002, an estimated 208,000 new cases of kidney cancer were diagnosed globally.⁹

About Pazopanib and Clinical Development

Pazopanib has a broad clinical program across multiple tumor types, with study details available at www.clinicaltrials.gov. Programs currently underway in advanced RCC include a head-to-head comparison trial with sunitinib in patients with no prior drug treatment. More than 2,000 patients have been treated to date in clinical trials.

GSK is dedicated to developing effective treatment options for oncology patients. GSK has a pipeline and portfolio of fundamental and innovative medicines seen across the industry.

GSK in Oncology

GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s revolutionary ‘bench to bedside’ approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centers. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com. 

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Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2008.

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1. Sternberg C, et al. Abstract #5021 – A Randomized, Double-blind Phase III Study of Pazopanib in Treatment-naive and Cytokine-pretreated Patients with Advanced Renal Cell Carcinoma (RCC). To be presented orally at the 2009 American Society of Clinical Oncology annual meeting.

2. NCI. Dictionary of Cancer Terms. “Progression Free Survival.” Available at:

    http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=44782. Accessed April 21, 2009.

3. ASCO. 2009 Meeting Planner. “pazopanib.” Available at: http://meetingplanner.asco.org/. Accessed April 21, 2009.

4. Data on file, GSK

5. Hutson, T, Figlin, R, Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies. The Oncologist. 2008; 13: 1084-1096.

6. Sonpavde, G. and Hutson, T. Pazopanib: A Novel Multitargeted Tyrosine Kinase Inhibitor. Curr Oncol Rep. 2007;Mar9(2):115-9.

7. American Cancer Society. What is Anti-Angiogenesis Treatment? Available at http://www.cancer.org/docroot/ETO/content/ ETO_1_4X_What_Is_Antiangiogenesis_Therapy.asp?sitearea=ETO. Accessed April 21, 2009.

8. American Cancer Society. “What is Kidney Cancer (Adult) – Renal Cell Carcinoma?” Available at http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_kidney_cancer_22.asp?sitearea=. Accessed April 21, 2009.

9. Parkin M, Bray F et al. Global Cancer Statistics. CA Cancer J Clin. 2002;55:74-108.