New Breast Cancer Treatment Available in Italy

HATFIELD, England, January 26, 2012 /PRNewswire/ --

Halaven^® (eribulin) increases life expectancies for women with locally advanced or metastatic breast cancer

Halaven^® (eribulin), a novel treatment for patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapeutic regimens for advanced disease, is now available under national reimbursement in Italy. 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 in patients with heavily pre-treated* advanced breast cancer when compared to an active control in the EMBRACE clinical trial.^[2]

Breast cancer is now the most common cancer in Italy with more than 47,500 cases diagnosed annually, and is the leading cause of death among women in Italy and worldwide.^[3,4] However, breast cancer mortality rates in Italy have shown a decline from the early 1990s, which is mainly attributable to advancements in treatments and the role of screening in detecting the cancer at an earlier stage.^[5,6]

"There is still a clear unmet need for new treatment options for women with heavily pre-treated metastatic or locally advanced breast cancer. The launch of eribulin in Italy marks a significant medical advance in a setting where there is currently no standard of care. Eribulin is an effective and well tolerated option that has been shown to extend life, offering women precious additional time to spend with their family and loved ones," commented Professor Stefania Gori, AIOM Board Member.

"The reimbursement of eribulin in Italy is a positive step for women living with metastatic breast cancer who would have otherwise been faced with limited treatment options. Access to this novel chemotherapy means that eligible patients will benefit from a new treatment which significantly increases their survival, providing them with valuable extra time with their families. We are very proud to bring this new treatment to Italy, and are committed to improving the lives of our patients," commented Laura Forni, Oncology Business Unit Head for Italy, Eisai Europe Ltd.

Discovered and developed by international pharmaceutical company Eisai, eribulin is a non-taxane, microtubule dynamics inhibitor and a synthetic analogue of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai.^[7] Results of the pivotal Phase III study, EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389), showed that patients treated with eribulin survived a median of 2.5 months longer than patients who received TPC (overall survival of 13.1 months vs. TPC 10.6 months, respectively p=0.014).^[1,2] An updated analysis demonstrated that patients treated with eribulin survived a median of 2.7 months longer than patients who received TPC (eribulin 13.2 months vs. TPC 10.5 months, nominal p=0.014).^[1,2] TPC represents active treatment options currently used by doctors in real world clinical practice.

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]

Eribulin received European Commission approval on 17 March 2011 based on the results of the EMBRACE study. Eribulin is approved in the European Union, USA, Switzerland, Japan, and Singapore. Eribulin is currently commercially available in Austria, Denmark, Finland, Germany, Japan, Norway, Sweden, Singapore, Switzerland, United Kingdom, and the USA.

Eisai's 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 low molecular weight organic compounds, therapeutic vaccines, monoclonal antibody-based therapies, biologics, and supportive care agents for cancer across multiple indications. Through these efforts, Eisai will make further contributions to addressing the diversified needs of and increasing the benefits provided to patients and their families as well as healthcare professionals as it seeks to fulfill its human health care (hhc) mission.

Notes to Editors

Halaven^® is the EU trade name for eribulin.

*Heavily pretreated metastatic breast cancer is defined as locally advanced or metastatic breast cancer that has progressed following use of at least two chemotherapeutic regimens for advanced disease. Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments.

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

EMBRACE 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 locally recurrent or 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.^[2]

In the Phase III EMBRACE study population, eribulin was shown to prolong overall survival in heavily pre-treated patients with metastatic breast cancer by 2.5 months compared to patients receiving TPC (eribulin 13.1 months vs. TPC 10.6 months p=0.014).^[1,2] An updated analysis, demonstrated a statistically significant improvement of 2.7 months in median overall survival for patients receiving eribulin compared to those receiving TPC (eribulin 13.2 months vs. 10.5 months, nominal p=0.014)^[1]

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 (nominal p=0.009).^[2]

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 (neutropenia), 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. Neutropenia only led to eribulin discontinuation for 0.6% patients. Death due to serious side effects, discontinuation and dose interruptions to treatment were less common in the eribulin arm of the trial compared with the TPC arm.^[2]

Metastatic Breast Cancer
Metastatic breast cancer is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body. In Europe, approximately 6% of breast cancers are metastatic at diagnosis with a 5-year survival rate of 21%.^[8]

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.^[1] 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.

Eisai in Oncology

Eisai is dedicated to discovering, developing and producing innovative oncology therapies that can make a difference and impact the lives of patients 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. 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, biologic and supportive care agents for cancer across multiple indications.

About Eisai

Eisai is one of the world's leading R&D-based pharmaceutical companies that has defined its 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:

• Neuroscience: Alzheimer's disease, multiple sclerosis, neuropathic pain, epilepsy, depression, etc
• Oncology: Anticancer therapies; tumour regression, tumour suppression, antibodies, etc and Supportive cancer therapies; pain relief, nausea, etc
• Vascular/Immunological Reaction: Acute coronary syndrome, atherothrombotic disease, sepsis, rheumatoid arthritis, psoriasis, Crohn's disease, etc

With operations in the U.S., Asia, Europe and its domestic home market of Japan, we employ more than 11,000 people worldwide. In Europe, Eisai undertakes sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic, Hungary, Slovakia and the Netherlands.

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

References

1. Summary of Product Characteristics Halaven (March 2011). Available at: http://www.medicines.org.uk/EMC/medicine/24382/SPC/Halaven+0.44+mg+ml+solution+for+injection

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. Grande et al. Regional estimates of breast cancer burden in Italy. Tumori 2007; 93: 374-379

4. Globocan 2008 http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=380. Last acccessed: November 2011

5. Levi F, Bosetti C, Lucchini F, Negri E, La Vecchia C: Monitoring the decrease in breast cancer mortality in Europe. Eur
J Cancer Prev, 14: 497–502, 2005

6. Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C: Cancer mortality in Europe, 1995-1999, and an overview of trends
since 1960. Int J Cancer, 110: 155–169, 2004

7. Jordan MA et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther 2005;4:1086–95

8. Cardoso, M. and Castiglione F. Locally recurrent or metastatic breast cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. On behalf of the ESMO Guidelines Working Group. Ann Oncol (2009) 20 (suppl 4): iv15-iv18