GSK receives positive opinions in Europe for Tyverb® (lapatinib) and Votrient™ (pazopanib)
London UK - GlaxoSmithKline (GSK) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued two positive opinions in the European Union for two of its cancer medicines.
The CHMP has issued a positive opinion for the authorisation of a new therapeutic indication for Tyverb® (lapatinib) in the European Union. Lapatinib, in combination with an aromatase inhibitor (AI), is indicated for the treatment of post-menopausal women with hormone receptor (HR)-positive, HER2 (ErbB2) over-expressing metastatic breast cancer and for whom chemotherapy is currently not intended. The patients in the registration study were not previously treated with trastuzumab or an aromatase inhibitor.
The CHMP has also recommended the conditional marketing authorisation for VotrientTM (pazopanib), for the first-line treatment of advanced RCC and for patients who have received prior cytokine therapy for advanced disease.Once approved, both medicines will provide new, oral, targeted treatment options for eligible patients in Europe.
“In the past three months, the CHMP has issued four positive opinions for innovative cancer and haematology treatments researched and developed by GSK. We are proud that the rapid pace of our development programme is delivering products that may make a difference for those patients who continue to try and overcome these two types of cancers, which are challenging diseases to treat.” said Eddie Gray, President, GSK Pharmaceuticals Europe.
Lapatinib, first-line combination treatment, delays disease progression
The positive opinion from the CHMP is based on the results of study EGF30008. This randomised Phase III trial evaluated lapatinib, in combination with letrozole, in women with HR-positive metastatic breast cancer which may or may not also over-express the HER2/ErbB2 receptor.1,2 The results showed that combination therapy provided a significant improvement in progression-free survival (defined as time from starting treatment to disease progression or death due to any cause; PFS) compared with letrozole plus placebo, in patients with HR-positive, ErbB2 over-expressing tumours.1 Patients given lapatinib plus letrozole experienced a median 8.2 months of PFS, compared with 3 months for those in the letrozole plus placebo group.1
The side-effects observed with lapatinib plus letrozole were principally diarrhoea and rash, which were generally grade 1 or 2 in severity and were manageable.1 Nausea and vomiting also commonly occurred, as well as loss of appetite and fatigue. The safety profile of lapatinib was consistent with previously reported results from trials of lapatinib in the advanced or metastatic breast cancer population.1
Pazopanib significantly improved progression-free survival over placebo
The CHMP positive opinion for a conditional marketing authorisation is based on data from a pivotal double-blind, Phase III study of 435 patients with advanced kidney cancer who had either received no prior drug treatment or had failed a cytokine-based treatment.3
The results showed that pazopanib significantly improved progression-free survival compared to placebo, regardless of whether or not they had received prior therapy with cytokines. In the overall treatment population patients receiving pazopanib experienced 9.2 months of median PFS, compared with 4.2 months for those in the placebo group. Treatment-naïve patients who received pazopanib experienced 11.1 months of median PFS, versus 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with pazopanib versus 4.2 months with placebo.3.
The majority of adverse events seen in the trial were mild to moderate, the most common (with incidence of 20% or more) being diarrhoea, hypertension, hair colour change, nausea, anorexia, and vomiting. The most common grade 3 or 4 adverse events (incidence more than 2%) were diarrhoea (4%), hypertension (4%), and loss of strength (asthenia) (3%). The most common grade 3/4 chemistry abnormalities were liver enzyme elevations, such as ALT and AST. Most cases of drug-induced liver enzyme elevations were asymptomatic and occurred within the first 4 months of treatment. Certain class effects including proteinuria, thrombocytopenia, hypothyroidism, hand-foot syndrome, and mucositis/stomatitis occurred with an incidence of fewer than 10% each, with grade 3/4 events reported in less than 1% of patients.3
About conditional marketing authorisation
A conditional marketing authorisation is granted to a medicinal product with a positive benefit/risk assessment that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. A conditional marketing authorisation is renewable annually.
As part of the conditions of the conditional marketing authorisation for pazopanib, GSK will be required to provide further data comparing pazopanib with sunitinib. This study is ongoing.
Lapatinib is the first oral, small-molecule, dual-targeted therapy for metastatic breast cancer that over-express ErbB2. Over-expression of ErbB2 has been reported in a variety of human tumours and is associated with poor prognosis and reduced overall survival. Lapatinib inhibits the tyrosine kinase enzyme activities of ErbB1 and ErbB2, which blocks a series of biochemical signals associated with tumour growth.
Lapatinib, in combination with capecitabine, is authorised in more than 90 countries worldwide for the treatment of patients with advanced or metastatic breast cancer, whose tumours over-express ErbB2. Patients should have progressive disease following prior therapy, which must include an anthracycline, a taxane, and trastuzumab in the metastatic setting.
GSK is pursuing a comprehensive breast cancer clinical development programme evaluating lapatinib both alone and in combination with other therapies like chemotherapy and other targeted agents across the spectrum of ErbB2-positive breast cancer, from early to metastatic breast cancer. Trials are also ongoing in a range of other solid tumours thatover-express ErbB1 and/or ErbB2.
About metastatic breast cancer
Metastatic breast cancer describes stages of the disease when cancer cells break away from a primary breast tumour and spread to other parts of the body via the bloodstream or lymphatic system. The most common areas of the body for breast cancer cells to spread to are the bone, liver, lung, and brain. The lymph glands in the armpits or lower neck may also be affected. The five-year relative survival rate is lower among women with a more advanced stage of cancer at diagnosis 4 with the median survival for women treated for metastatic breast cancer about 2-4 years.5
Pazopanib, a once-daily, oral medication, is an angiogenesis inhibitor, which may help prevent the growth of new blood vessels as well as acting directly on the cause of renal cell cancer. Pazopanib is currently being investigated in a broad clinical development programme across multiple tumour types.
In adults, 85-90 per cent of kidney cancers are RCC.6In the EU, there were an estimated 63,300 new cases of kidney cancer and 26,400 deaths due to kidney cancer in 2006.7 RCC is the most common type of kidney cancer 8. The incidence is rising throughout the world9, with 208,000 new cases diagnosed annually and over 100,000 deaths.10 More than 10% of new cases are diagnosed in Western Europe.11Nearly 30% of patients with RCC are found to have metastatic disease at diagnosis.12
About GlaxoSmithKline 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 centres. 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
Notes to editors
Tykerb® is the registered trade mark of the GlaxoSmithKline group of companies in the United States and the countries outside Europe. Tyverb® is a registered trademark of the GlaxoSmithKline group of companies in the European Union.
Votrient® is a registered trade mark of the GlaxoSmithKline group of companies in the US and the proposed trade name in Europe, Asia-Pacific, Japan and emerging countries.
This press release is intended for business journalists and analysts/investors. Please note that this release may not have been issued in every market in which GSK operates.
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12. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115-124.
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