Women With Advanced Breast Cancer Denied Life-extending Treatment Halaven(R) (black triangle drug) (Eribulin)

HATFIELD, England, November 17, 2011 /PRNewswire/ --

Eisai Considers Grounds to Appeal the NICE Decision

The National Institute for Health and Clinical Excellence (NICE) today published its final appraisal determination (FAD) on Halaven^® (eribulin). This final appraisal does not recommend NHS funding of eribulin in England and Wales.^[1] Eribulin is a new treatment approved for the treatment of patients with locally advanced or metastatic breast cancer whose disease has progressed after at least two chemotherapeutic regimens for advanced disease.^[2] Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments.

There is a clear unmet need for new treatment options for women with heavily pre-treated metastatic breast cancer whose disease has continued to progress despite receiving several lines of chemotherapy. Eribulin is the first single agent chemotherapy to demonstrate a prolongation of overall survival in late lines of therapy in metastatic breast cancer.^[3] It has an expected and manageable safety profile which is in line with other single agent drug treatments for advanced breast cancer.^[3] Despite the need for new treatment options and the proven benefits of eribulin in improving overall survival, NICE has issued a negative recommendation for the use of eribulin on the NHS.  Eisai intends to assess the FAD to determine grounds for appeal and will do all it can to ensure patient access to eribulin.

Professor Chris Twelves, Deputy Director, Cancer Research UK Clinical Centre in Leeds commented; "Eribulin has challenged the notion that improved overall survival is an unrealistic outcome for women with heavily pre-treated advanced breast cancer. The EMBRACE trial not only demonstrated that eribulin provides an improvement in median overall survival compared to single agent treatments, but that this survival benefit is not outweighed by any unexpected or unmanageable side effects, an important aspect for any treatment in this setting."

Nick Burgin, European Director of Market Access, Eisai said; "We are dismayed with this final NICE appraisal as it denies women access to a treatment that is proven to prolong life and provides an opportunity for the NHS to improve cancer outcomes in metastatic breast cancer patients. Eribulin is an innovative agent currently being offered to the NHS at the lowest price in the world. Eisai has tried to make eribulin affordable in England and Wales and has offered a discount on the price of the new drug.  We feel that patients should not be unable to access a life-prolonging drug like eribulin on the basis of an arbitrary threshold of cost per quality adjusted life year (QALY) used by NICE and we plan to appeal this decision."

Eribulin is already available and reimbursed in a number of countries throughout Europe and this negative NICE decision further demonstrates the inequality of access to cancer treatments for patients in the UK compared to other countries. The NICE decision restricts NHS access to eribulin in England and Wales, but fortunately the new drug can be accessed in England through the Cancer Drugs Fund where it has been approved in four of the 10 regions.  However, this denies access to those living outside these regions or in other parts of the UK where the Cancer Drugs Fund system does not exist.

Results of the pivotal Phase III study, EMBRACE, showed that patients treated with eribulin survived on average 2.7 months longer than patients who received 'treatment of physician's choice' (TPC) (eribulin 13.2 months vs. TPC 10.5 months, nominal p=0.014).^[2] TPC represents active treatment options currently used by doctors in real world clinical practice.

A further pre-planned analysis of region 1 (North America/Australia/Western Europe)
of the Phase III EMBRACE clinical trial was also carried out. The results showed a significant overall survival benefit of eribulin over TPC of 3.0 months (nominal p=0.031).^[3]Ten UK trial centres were included within region 1 and this further analysis was carried out as the patients in this region were felt to best represent how patients in the UK are managed.

Eribulin is approved in the European Union, USA, Switzerland, Japan, and Singapore. Eribulin is currently commercially available in Austria, Denmark, Finland, Germany, Japan, Netherlands, Norway, Portugal, Spain, Sweden, Singapore, Switzerland, United Kingdom, and the USA.

Notes to Editors

Halaven is the EU trade name for eribulin.

Eribulin was launched on 20 April 2011 in the UK and is commercially available in the UK. It is funded via the Cancer Drug Fund in four regions in England and through private insurance companies.

Global Phase III Clinical Study (EMBRACE)

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 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 (97%) of patients in the TPC arm received chemotherapy.^[2]

In the total Phase III EMBRACE study population, eribulin was shown to prolong 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).^[3] 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=0.031).^[3]

Eisai also sumitted data on the post capecitabine population which includes 554 patients (74% of the trial population)  that showed a 2.9 months improvement in survival (p=0.018) vs TPC.

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 interuptions to treatment were lower in the eribulin arm of the trial compared with the TPC arm ^[2]

Metastatic Breast Cancer

Breast cancer is now the most common cancer in the UK and the lifetime risk of being diagnosed with breast cancer is 1 in 8 for women in the UK.^[4] In 2008, almost 47,700 women were diagnosed with breast cancer, around 130 women a day.^[5]

Metastatic breast cancer is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body. Approximately five percent of women with breast cancer will have metastatic disease at the time of diagnosis^[5] and 35% will develop metastatic disease at some point after the initial diagnosis.^[6] Only 13% of women presenting with metastatic breast cancer will survive beyond five years.^[6]

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.^[3] 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. National Institute for Health and Clinical Excellence. Final appraisal determination. Eribulin for the treatment of locally advanced or metastatic breast cancer. November 2011

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

3. 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

4. Cancer Research UK. Cancer Statistics - Key Facts. Available at: http://info.cancerresearchuk.org/cancerstats/types/breast/ (Accessed 1 April 2011)

5. Cancer Research UK. Statistics and outlook for breast cancer. Available at: http://www.cancerhelp.org.uk/type/breast-cancer/treatment/statistics-and-outlook-for-breast-cancer (Accessed 1 April 2011)

6. Synovate track the usage of anti-cancer drugs, through a representative panel of cancer specialists completing forms directly from patient medical records in each country, including the UK. Eisai data on file.