Innovative Metastatic Breast Cancer Treatment Halaven® (eribulin) is Available in Belgium

HATFIELD, England, October 1, 2013 /PRNewswire/ --

Country with highest global rate of breast cancer^[1] welcomes treatment option with proven overall survival benefit^[2]

Halaven^® (eribulin) has today received reimbursement approval in Belgium as a novel treatment for patients with metastatic breast cancer. Eribulin is the first, single-agent chemotherapy to demonstrate a prolonged overall survival in patients with heavily pre-treated advanced breast cancer, compared to other single agent chemotherapies^[2].

"The availability of eribulin in Belgium is a significant milestone for women with advanced breast cancer," says Professor Ahmad Awada, Principal Study Investigator and Head of the Medical Oncology Clinic at Jules Bordet Institute, Brussels, Belgium. "Many women with metastatic breast cancer need urgently new treatment options.  Eribulin goes some way to address this unmet need and provides patients and clinicians with an option that has a proven overall survival benefit in heavily pretreated patients."

Belgium has a higher incidence of breast cancer than any other country in the world with around one in every 10 women developing breast cancer each year^[1]. Of these cases, metastatic breast cancer develops in 30 percent of women with an estimated 2,500 women dying from the condition.^[3]

"We are pleased that the Belgian health authorities recognise the innovative drug status and clinical value eribulin may offer to women with locally advanced or metastatic breast cancer. The reimbursement in Belgium underscores the potential importance of this treatment and is a positive step forward for women affected by this disease. Eisai will work closely with local health authorities to ensure that women in Belgium have rapid access to a treatment that has a proven overall survival benefit," says Dr Nicolas Kormoss, Medical Director for Belgium and Luxembourg, Eisai EMEA.

Eribulin received European Commission approval on 17 March 2011 based on the results of the pivotal Phase III EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389) study.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 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]

The most commonly reported adverse reactions among patients treated with eribulin were asthenia (fatigue), neutropenia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms and legs), nausea and constipation.^[2]

Eisai is committed to developing and delivering highly beneficial new treatments to help improve the lives of people with cancer. Built on scientific expertise, Eisai 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.

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.^[4],[5],[6] 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.^[7] 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.^[8],[9]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. http://www.wcrf-uk.org/research/cancer_statistics/world_cancer_statistics_breast_cancer.php Last accessed August 2013

2. Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. The Lancet. 2011; 377: 914 -923

3. Globocan 2008 statistics. http://globocan.iarc.fr/factsheet.asp#WOMEN [http://globocan.iarc.fr/factsheet.asp ]. Last accessed July 2013.

4. 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  

5. 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

6. 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

7. 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

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

9. 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 April 2013.

Date of preparation: October 2013

Job code: Halaven-UK0213