GlaxoSmithKline (GSK) announced that the European Commission (EC) has granted Marketing Authorisation for HYCAMTIN(R) (topotecan powder for concentrate for solution for infusion) for the treatment of patients with relapsed small cell lung cancer (SCLC) for whom re-treatment with the first-line regimen is not considered appropriate. HYCAMTIN(R) is the first drug to be approved in Europe that is specifically indicated for the treatment of relapsed SCLC. Data from the HYCAMTIN(R) clinical trials show that treatment with HYCAMTIN(R) is associated with prolonged survival and quality of life compared to best supportive care in patients battling the disease.

The marketing authorisation follows a positive opinion in November 2005 by the European Committee for Human Medicinal Products (CHMP) for HYCAMTIN(R).

HYCAMTIN(R) is a compound already familiar to oncologists as a treatment for relapsed ovarian cancer. The chemotherapeutic agent belongs to a class of drugs known as topoisomerase I (topo-I) inhibitors, and works by inducing DNA damage which results in the death of dividing cells. Because two thirds of patients with SCLC already have extensive disease at the time of diagnosis and nearly all patients with extensive disease eventually relapse, approval of HYCAMTIN(R) is a significant step forward in widening options for patients.

"The oral form of HYCAMTIN(R) has shown promising and unexpected results in improving symptoms and lengthening the life of patients with relapsed SCLC, a disease that is traditionally associated with a grave outlook for patients," says Dr. Mary O'Brien, Head of the Lung Cancer Unit, The Royal Marsden NHS Foundation Trust, UK. "This approval of intravenous HYCAMTIN(R) will now provide physicians and our patients an important new treatment option in SCLC."

"HYCAMTIN(R) appears to provide greater symptom improvement than CAV. The regimen has no neurotoxicity and in a randomised study, SCLC patients experienced a significant improvement in breathing difficulties and anorexia," says Dr J. von Pawel, Head, Department of Oncology, Asklepios Kliniken Munchen-Gaunting, Germany and an investigator in the study. "HYCAMTIN(R) is an important step forward in terms of improving the quality of life for SCLC patients and essentially allows them to make the best use of the time they have left."

European approval was principally based on three key Phase III studies. The first study (protocol 090) compared the safety and efficacy of HYCAMTIN(R) to the triple combination cyclophosphomide, doxorubicin and vincristine (CAV) in patients with sensitive SCLC. Median overall survival was comparable between the two arms of the study (25.0 versus 24.7 weeks, p = 0.80).

The second study (protocol 396) compared the safety and efficacy of an oral formulation of topotecan versus IV HYCAMTIN(R) in patients with sensitive SCLC. Median overall survival was comparable between the two arms (33.0 versus 35.0 weeks, Hazard Ratio = 0.98) and both treatments were generally well-tolerated.

The third study (protocol 478) was conducted to prove the survival benefit of second-line chemotherapy for relapsed SCLC patients. The study was conducted using oral HYCAMTIN(R) plus best supportive care and compared safety and efficacy to best supportive care (BSC) alone. Median overall survival for HYCAMTIN(R) plus BSC was 25.9 weeks compared to 13.9 weeks for patients who received BSC alone (p = 0.01).

Mike Unger, Chief Executive, The Roy Castle Lung Cancer Foundation, UK comments, "Small cell lung cancer is a particularly devastating disease, with a very serious outlook for those suffering from it. SCLC comprises 25% of all lung cancers and at the moment there are very few treatment options. The approval of HYCAMTIN(R) by the European Committee for Human Medicinal Products is a very exciting development and will give support and benefits to many patients in the UK and across Europe. The Foundation looks forward to further clinical research and experience concerning HYCAMTIN(R)."

"HYCAMTIN(R) offers an important new therapeutic option for patients in Europe who are faced with managing this devastating disease," said Andrew Witty, President, Pharmaceuticals Europe, GSK. "This approval is another example of GSK's continued commitment to researching and developing an industry leading oncology portfolio to address the unmet medical needs of cancer patients around the world."

About Small Cell Lung Cancer

Lung cancer is the most common cancer in the world attributing to 13.2% of all cancer cases.[i] About 20 out of every 100 cases diagnosed are small cell lung cancer.[ii] Of all those diagnosed with small-cell lung cancer, around one in three have limited disease at the time of diagnosis. Two out of three already have extensive disease at the time of diagnosis. Of those who have limited disease and have chemotherapy, between 35 - 40% will be alive two years later. People with extensive disease are also treated with chemotherapy, but unfortunately the survival rate is even lower. Most only survive another ten to twelve months.[iii]

Globally the highest rates of lung cancer in men are found in Europe, especially eastern Europe, and North America. For women, the highest rates are found in North America and European countries such as Denmark, Hungary, Iceland and the UK.[iv]

About HYCAMTIN(R)

HYCAMTIN(R) (topotecan powder for concentrate for solution for infusion) is a chemotherapeutic agent that belongs to a class of drugs known as topoisomerase I (topo-I) inhibitors. Topo-I is an enzyme essential for the replication of DNA, and therefore cell division, in both normal and cancer cells. Interaction between topo-I and HYCAMTIN(R) results in damage to the cell's cancerous genetic material and the death of dividing cancer cells.

HYCAMTIN(R) is already registered in the European Union, and 59 other countries around the world for the treatment of relapsed ovarian cancer following platinum-based therapy. More than 230,000 patients have been treated with HYCAMTIN(R) since its launch in 1996. More information on HYCAMTIN(R) can be found at www.emea.eu.int

For further product information please access the Electronic Medicines Compendium at www.medicines

Important Safety Information

HYCAMTIN(R) can suppress the body's ability to produce blood cells, in particular the white blood cells which fight infection. This condition is known as neutropenia. The clotting elements (platelets) can also be decreased, a condition known as thrombocytopenia. HYCAMTIN(R) is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or any of its ingredients. HYCAMTIN(R) should not be used in patients who are pregnant or breast-feeding, or in those with severe bone marrow depression.

About GlaxoSmithKline

GlaxoSmithKline (NYSE: GSK) is one of the world's leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling cancer patients to do more, feel better and live longer. For more information, visit gsk.

[i] Boyle P, Ferlay J. Cancer incidence and mortality in Europe 2004. Annals of Oncology, 2005. 16: 481-488
[ii] Onkos Plus Study #5, Small Cell Lung Cancer, December 2004, pg 7
[iii] wwwncerhelp/help/default.asp?page=2965#small, accessed January 2006
[iv] GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide (2002 estimates), 2005

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