Life-extending Metastatic Breast Cancer Treatment Now Available in the Republic of Ireland

HATFIELD, England, January 6, 2014 /PRNewswire/ --



Halaven^® (eribulin) has today received reimbursement approval in the Republic of Ireland as a treatment for patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapeutic regimens for advanced disease. Prior therapy should have included two common types of chemotherapy, an anthracycline and a taxane, unless patients were not suitable for these treatments.^[1] Eribulin is the first, single-agent chemotherapy to demonstrate a prolonged overall survival benefit for metastatic breast cancer patients within this setting compared to other available single agent treatments.^[2]

"I am pleased that eribulin will be available to Irish public patients with advanced breast cancer," says Professor John Crown, Consultant Medical Oncologist at St Vincent's University Hospital, Dublin, Ireland. "It is active and offers the prospect of additional precious months of disease control to these women."

Breast cancer is the second most common form of cancer amongst Irish women.^[3] One in ten women in Ireland will develop breast cancer and more than 2,600 new cases are diagnosed each year.^[3] In almost ten percent of cases,^[4] breast cancer is metastatic at diagnosis with a five-year survival rate of only 21 percent.^[5] Ireland has the fourth highest breast cancer mortality rate across 30 European countries,^[4] however a recent report, published by St James's Hospital Dublin, has shown significant improvements in cancer survival rates over the last decade.^[6]

Gary Hendler, President and CEO, Eisai EMEA commented: "Eribulin will play an important role in improving the treatment and outcomes of metastatic breast cancer in Ireland. We are delighted that the innovative drug status and clinical value of eribulin has been recognised and that women will now have access to the drug. Its reimbursement in Ireland underscores the need to ensure that women with metastatic breast cancer have access to treatments that are best suited to their needs."

Eribulin received European Commission (EC) approval on 17 March 2011 based on the results of the Phase III EMBRACE study (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389).^[2] Eribulin is now available in 50 countries worldwide.

In the EMBRACE study population (n=762), eribulin was shown to prolong overall survival in heavily pre-treated patients with metastatic breast cancer by 2.5 months compared to patients receiving Treatment of Physicians Choice (TPC), representing a mix of real-life treatment choices (eribulin 13.1 months vs. TPC 10.6 months, HR 0.81 (95% CI 0.66, 0.99) p=0.041).^[2] Updated data from the trial confirmed these results, showing that patients treated with eribulin survived a median of 2.7 months longer than patients who received treatment of physician's choice (overall survival of 13.2 months versus 10.5 months, respectively, HR 0.81 (95% CI 0.067, 0.96), nominal p=0.014).^[2] A pre-planned analysis of patients from Region 1 of the study (North America/Western Europe/Australia) showed a significant overall survival benefit of eribulin over TPC of 3.0 months (p=0.009).^[2]

Eisai is dedicated to discovering, developing and producing innovative oncology therapies that can make a difference and impact the lives of women and their families. This passion for people is part of Eisai's human health care (hhc) mission, which strives for better understanding of the needs of patients and their families to increase the benefits health care provides.

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Notes to Editors

Halaven^® (eribulin)

Eribulin is a non-taxane, microtubule dynamics inhibitor indicated for the treatment of patients with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane.Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequesters tubulin into non-productive aggregates. Research indicates that eribulin may have a novel inhibitory effect on tumour metastasis by suppressing the expression in epithelial-mesenchymal transition (EMT) gene sets.^[7],[8],[9] EMT is a phenomenon in which cells acquire characteristics that allow them to develop into tumours and is highly significant in the infiltration and metastasise of cancer.

Further analysis of the MOA for eribulin has shown that eribulin also improves blood perfusion in tumour tissues meaning that it increases the amount of oxygen available to tumours.^[10] When tumours are deprived of oxygen they are more likely to metastasise and as such eribulin works to inhibit metastasis. Following treatment with eribulin, tumours were less aggressive and invasive.

Global Phase III Clinical Study 305 (EMBRACE)^[2]

EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389) was an open-label, randomised, global, multi-centre, parallel two-arm study designed to compare overall survival in patients treated with eribulin versus a Treatment of Physician's Choice (TPC) arm. TPC was defined as any single-agent chemotherapy, hormonal treatment or biologic therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice. The study included 762 patients with metastatic breast cancer who previously had been treated with at least two and a maximum of five prior chemotherapies, including an anthracycline and a taxane. The vast majority (96%) of patients in the TPC arm received chemotherapy.

In the total Phase III EMBRACE study population, eribulin was shown to prolong median overall survival in heavily pre-treated patients with metastatic breast cancer compared to patients receiving TPC by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI 0.067, 0.96) nominal p=0.014). A pre-planned analysis of patients from Region 1 of the study (North America/Western Europe/Australia) showed a significant median overall survival benefit of eribulin over TPC of 3.0 months (nominal p=0.031).

The most commonly reported adverse reactions among patients treated with eribulin in the EMBRACE study were fatigue (asthenia), a decrease in infection-fighting white blood cells (neutropaenia), hair loss (alopecia), numbness and tingling in arms and legs (peripheral neuropathy), nausea and constipation. Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in less than 5% of the patients involved in the EMBRACE trial. Neutropaenia only led to eribulin discontinuation for 0.6% patients. Death due to serious side effects, discontinuation and dose interruptions to treatment were lower in the eribulin arm of the trial compared with the TPC arm.

Metastatic Breast Cancer

Over 300,000 women are diagnosed with breast cancer in Europe every year, of whom about one third subsequently develop metastatic disease.^[11],[12]Metastatic disease is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body.

Eisai in Oncology

Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, and biologic and supportive care agents for cancer across multiple indications.

About Eisai

Eisai is one of the world's leading research and development (R&D) based pharmaceutical companies and we define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call human health care (hhc).

Eisai concentrates its R&D activities in three key areas:

• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc.
• Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight loss
• Vascular/Immunological reaction including: thrombocytopenia, rheumatoid arthritis, psoriasis, inflammatory bowel disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 10,000 people worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, Russia and the Middle East.

For further information please visit our web site http://www.eisai.co.uk

References

1. SPC Halaven (updated August 2013). Available at: http://www.medicines.org.uk/emc/medicine/24382. Last accessed December 2013

2. Cortes J, et al. The Lancet. 2011; 377: 914-923

3. Irish Cancer Society. Breast Cancer - the key facts. Available from:

 http://www.cancer.ie/reduce-your-risk/breast-cancer-what-you-should-know/key-facts (Last accessed October 2013)

4. National Medicines Information Centre, St James' Hospital, Ireland

http://www.stjames.ie/GPsHealthcareProfessionals/Newsletters/NMICBulletins/NMICBulletins2012/breast%20cancer%202012%20amend.pdf (Last accessed October 2013)

5. Cardoso, M., Castiglione F. Ann Oncol 2009; 20 Suppl 4: iv15-iv18

6. Cancer Audit Programme Team, St James's Hospital. Ten year cancer audit report 2003-2013

7. McCracken P.J, Ito. K, Yanagimachi M, et al. Eribulin alters vascular function in human triple-negative (TN) breast MX-1 and MDA-MB-231 tumor xenograft models as measured by DCE-MRI. AACR abstract 2013 abstract # 4502 

8. Dezso Z, Oestreicher J, Weaver A et al. Gene expression profiling (GEP) reveals Epithelial Mesenchymal Transition (EMT) genes selectively differentiating eribulin sensitive breast cancer cell lines. AACR abstract 2013 abstract # 1522

9. Agoulnik SI, Oestreicher JL, Taylor NH et al. Eribulin and Paclitaxel differentially affect gene expression profiling of blood vessel cells and in vitro angiogenesis in co-cultures of human endothelial cells with pericytes. AACR abstract 2013 abstract # 3830

10. Matsui J, Toyama O, Ino M et al. Eribulin caused re-modeling of tumor vasculature altering gene expression profiling in angiogenesis and Epithelial Mesenchymal Transition (EMT) signaling pathway of host cells within human breast cancer cell (BCC) xenografts in nude mice. AACR abstract 2013 abstract # 1413

11. World Health Organization. Atlas of Health in Europe. 2003. World Health Organization, Regional Office of Europe, Copenhagen, Denmark.

12. Cancer Research UK. Breast cancer incidence statistics. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/#world [ http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence ]. Last accessed October 2013.

Job code: Halaven-UK0220

Date of preparation: December 2013