Advanced Breast Cancer Treatment Halaven® (eribulin) Receives Reimbursement in Israel

HATFIELD, England, February 8, 2016 /PRNewswire/ --

Breast cancer is the most prevalent cancer in Israel, with one in eight women affected^[i]

Halaven^® (eribulin), a first-in-class treatment for women with locally advanced or metastatic breast cancer who have progressed after at least one prior chemotherapeutic regimen for advanced disease, has received reimbursement by the health authorities in Israel for the treatment of women with triple-negative breast cancer.  Prior therapy should have included an anthracycline and a taxane, unless patients were not suitable for these treatments.

Eribulin remains the only single agent chemotherapy to significantly improve overall survival in women with advanced breast cancer after anthracycline and taxane treatment compared to commonly used agents.^[ii] Eisai will continue to partner with the Neopharm group to ensure eribulin's continued availability to women in Israel.

Approximately 4500 women in Israel are diagnosed with breast cancer each year, with 900 expected to die from the disease.^[iii] The rate of breast cancer in Israel is higher than in most Organisation for Economic Co-operation and Development (OECD) countries.^[iv] Metastatic breast cancer is a very difficult condition to treat and only 15% of women will survive beyond five years.^[v]

"We are grateful to the Israeli health authorities for recognising the needs of women with advanced breast cancer in their decision. Today is an important day for these women and for all those who treat them. Eribulin has demonstrated efficacy in women with advanced breast cancer and may offer people with breast cancer more time to spend with their loved ones. Given the rates of breast cancer in Israel, the fact that eribulin will now be reimbursed in the country is very welcome news indeed," comments Gary Hendler, CEO of Eisai EMEA and President, Global Oncology Business Unit.

"We are very pleased with this news and welcome the opportunity to continue to work in partnership with Eisai for the benefit of women with advanced breast cancer across Israel," states Mr. Efi Shnaidman, GeneraL Manager, Neopharm Israel.

The availability of eribulin in Israel underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well-being of people worldwide. Eisai is committed to oncology to address the unmet medical needs of patients and their families.

Notes to Editors 

Halaven^® (eribulin)  

Eribulin is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.

Eribulin is indicated for the treatment of women with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.^[vi]

Global Phase III Study 305 (EMBRACE)^[ii]

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 women treated with eribulin versus a 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 participants with metastatic breast cancer (MBC) 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 participants 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 women with MBC compared to women receiving TPC by 2.7 months (13.2 vs. 10.5 HR 0.81 (95% CI 0.67, 0.96) nominal p=0.014). A pre-planned analysis of participants 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 people 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 women involved in the EMBRACE trial. Neutropenia only led to eribulin discontinuation for 0.6%. 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.

Global Phase III Study 301^[vii] 

Study 301 was an open-labelled, randomised, two-parallel-arm, multicentre study of eribulin versus capecitabine in 1,102 women with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes, either in the (neo) adjuvant setting or for locally advanced or metastatic disease. Women in the study received zero to two previous chemotherapies for advanced disease.

The study opened in 2006 and the last patient was randomised in 2010. Patients were randomised to treatment with either eribulin 1.23mg/m^[2] (administered intravenously over two to five minutes on days 1 and 8, every 21 days) or capecitabine 1.25 g/m^[2], administered orally twice daily on day 1 to 14, every 21 days.

Study 301 had a co-primary endpoint of overall survival and progression free survival. The study demonstrated a trend favouring improved overall survival with eribulin compared to capecitabine in the ITT population, although the improvement was not statistically significant. Women treated with eribulin had a median overall survival of 15.9 months (HR 0.879; 95% CI: 0.770-1.003; p=0.056) versus 14.5 months with capecitabine. The trial did not meet the pre-specified endpoint for progression-free survival, with 4.1 and 4.2 months for eribulin and capecitabine (independent review) respectively (HR 1.079; 95% CI: 0.932-1.250; p=0.305).

1-, 2- and 3- year overall survival rates for eribulin versus capecitabine showed an early improvement which was maintained throughout the study (1 year, 64.4% eribulin vs 58.0% capecitabine (p=0.0351), 2 year 32.8% eribulin vs. 29.8% capecitabine (p=0.324), 3 year, 17.8% eribulin vs. 14.5% capecitabine (p=0.175).

Unlike studies conducted today, Study 301 included all women regardless of their human epidermal growth factor receptor 2 (HER2), oestrogen receptor (ER) or progesterone receptor (PR) status. Patients are usually tested for their HER2 status as there are now effective treatments specifically for patients with the HER2 mutation. HER2 positive patients would generally be treated with anti-HER2 positive targeted therapy. For women with HER2 negative MBC (n=755), overall survival was 15.9 months for eribulin vs. 13.5 months for capecitabine (HR 0.838; 95% CI: 0.715-0.983). In the HER2 positive population, overall survival was 14.3 months for eribulin vs. 17.1 months for capecitabine (HR; 95% 0.965; CI: 0.688-1.355).

Adverse events in Study 301 were consistent with the known profile of both drugs.

Metastatic Breast Cancer and the HER2 Protein 

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

HER2 is a protein that is found on the surface of cells. In HER2-positive breast cancer there is more (over expression) of this protein found on the surface of tumour cells compared with normal breast cells. This protein can be targeted with HER2 targeted therapies such as Herceptin, in people who overexpress HER2, but not in people with normal levels of HER2 protein (HER2-negative) breast cancer. Breast cancers are routinely tested for the presence of HER2 to decide the most appropriate treatment. Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for oestrogen receptor, progesterone receptor (<1%) and HER2 (<30%).

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 Co., Ltd. 

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. 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 our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology. 

As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit http://www.eisai.com.  

About Neopharm Group 

Neopharm Group, established in 1941, through its family of companies, is engaged in the research and development, manufacturing and sales of a broad range of products in the health care field in 60 countries around the world. We embrace the promotion of innovative ideas, products and services to advance health and well-being. Our family of companies operates in three major segments: Pharmaceutical, Consumer Healthcare, and Medical.  

The Pharmaceutical segment provides a complete spectrum of integrated services for international companies seeking to enter or expand their presence in the Israeli pharma, biotech and healthcare markets. For over 70 years we have grown the value of our products, consistently increased our turnover and enhanced our market leadership in Israel. We are considered the Israeli partner-of-choice and a one-stop-shop for multinational bio-pharma companies. Our success is based upon a track record of close collaboration with the world's leading multinational bio-pharma companies.

Neopharm is the exclusive representative and partner of leading multinational bio-pharma and consumer healthcare brands including: Abbott, Actelion, Alexion, Celgene, Johnson & Johnson, Pfizer Consumer Health among others.

Neopharm enjoys a sales turnover in excess of 400M $US in 2015 and employs 700 employees worldwide.

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

References 

i. Israel Cancer Association, Breast Cancer - http://en.cancer.org.il/template_e/default.aspx?PageId=7749 Accessed: January 2016 

ii. Cortes J 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 

iii. Israel Cancer Association, Breast Cancer - http://en.cancer.org.il/template_e/default.aspx?PageId=7749  Accessed: January 2016 

iv. The Jerusalem Post, Cancer tops list of deaths in Israel - http://www.jpost.com/Health-and-Science/Death-rate-from-heart-disease-down-80-percent-compared-to-1970s-332407  Accessed: January 2016 

v. Cancer Research UK, Breast Cancer - Outlook by Grade - http://www.cancerresearchuk.org/about-cancer/type/breast-cancer/treatment/statistics-and-outlook-for-breast-cancer#overall  Accessed: January 2016 

vi. SPC Halaven (updated June 2014). Available at: http://www.medicines.org.uk/emc/medicine/24382/SPC/Halaven+0.44+mg+ml+solution+for+injection/   Accessed: January 2016 

vii. Kaufman P et al. A Phase III, open-label, randomised, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Presented at 2012 CTRC-AACR San Antonio Breast Cancer Symposium 

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

ix. Cancer Research UK. Breast cancer incidence statistics. Available at:http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/#world  Accessed: January 2016