Draft Nice Guidance on Advanced Breast Cancer Treatment, Halaven(R) Black Triangle Drug (Eribulin)

HATFIELD, England, July 20, 2011 /PRNewswire/ --

The National Institute for Health and Clinical Excellence (NICE) today issued draft guidance on Halaven^® (eribulin) for public consultation. The draft guidance does not recommend NHS funding of eribulin, a treatment for locally advanced or metastatic breast cancer.

Eribulin is a novel treatment indicated for patients with locally advanced or metastatic breast cancer whose disease has progressed after at least two chemotherapeutic regimens for advanced and metastatic disease.^[1]  It was launched in the UK in April 2011 and some patients have already started to benefit from treatment. Before the approval of eribulin in the EU, no single treatment has demonstrated a statistically significant prolongation of median overall survival as shown in the clinical trial.^[2]

"We are hugely disappointed with the draft guidance issued by NICE. It has not recommended an innovative treatment for a vulnerable group of women with heavily pre-treated locally advanced or metastatic breast cancer, with a proven overall survival benefit," commented Nick Burgin, European Director of Market Access, Eisai. He adds; "Despite the UK price of eribulin currently being the lowest in the world, and a further patient access scheme agreement with the Department of Health which makes eribulin available at a discounted price, and unique real-world comparative data that has demonstrated overall survival, NICE’s unwillingness to approve this treatment is a real surprise."

There is a clear unmet need for treatments that improve overall survival for women with locally advanced or metastatic breast cancer, particularly those who do not respond or become refractory to treatments such as anthracyclines and taxanes and, in many cases, capecitabine.^[3]

Eribulin is approved in the European Union, USA, Switzerland, Japan, and Singapore. Eribulin is currently commercially available in Austria, Denmark, Finland, Germany, Netherlands, Norway, Portugal, Spain, Sweden, Singapore, Switzerland, United Kingdom, and the USA and will become commercially available in Japan on 19 July 2011.

The draft guidance is based on the Phase III data showing a median overall survival benefit of 13.1 months for patients receiving eribulin compared to 10.6 months for patients receiving ‘treatment of physician’s choice’ (TPC).^[4] The side-effect profile of eribulin was expected and manageable. The most commonly reported adverse reactions among patients were asthenia (fatigue), neutropenia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms and legs), nausea and constipation.^[1] Limited inference can be drawn from direct comparison of safety between patients treated with eribulin and those treated with TPC, as each of the therapies in the TPC group has a distinct safety profile. However, comparisons between eribulin and TPC showed that serious adverse events occurred in 25% of patients on eribulin and 26% of those on TPC, and adverse events leading to therapy discontinuation occurred in 13% of eribulin patients and 15% of TPC patients.

Professor Neville Davidson, Consultant Oncologist commented; "Having treated patients with eribulin, there were no unexpected side-effects in comparison with other treatments options in heavily pre-treated patients with locally advanced or metastatic breast cancer."

Pre-planned analysis of patients from geographical region 1 (North America/Western Europe/Australia) best represent how patients in the UK are managed and showed a significant overall survival benefit of eribulin over TPC of 3.0 months, nominal p=0.031 (updated analysis).^[4]

Eisai is currently evaluating the ACD and will be responding to the preliminary guidance to reverse the recommendations so that more patients can benefit from treatment with eribulin.

Notes to Editors

Halaven is the EU trade name for eribulin.

Eribulin was launched on 20 April 2011 and is commercially available in the UK. It is available via the Cancer Drug Fund 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]

The most common adverse reactions (incidence greater than or equal to 19%) among patients treated with Eribulin were asthenia (fatigue), neutropenia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms and legs), nausea and constipation. The most common serious side effect reported in patients receiving eribulin was neutropenia, with or without fever (occurring in 45% and 5% of patients respectively).The most common adverse reaction resulting in discontinuation of treatment with eribulin was peripheral neuropathy (five percent).^[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.^[5] In 2008, almost 47,700 women were diagnosed with breast cancer, around 130 women a day.^[4]

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^[6] and others with local and regional disease may eventually develop metastatic disease.^[7] An estimated 13 percent of women presenting with metastatic breast cancer will survive beyond five years.^[5]
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.

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 10,000 people worldwide, and reported consolidated sales of over £3.53 billion in FY2007, an increase of 8.9% year on year. 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 (updated March 2011). Available at: http://www.medicines.org.uk/EMC/medicine/24382/SPC/Halaven+0.44+mg+ml+solution+for+injection/

2. Jassem J, Carroll C, Ward SE, Simpson E, Hind D. The clinical efficacy of cytotoxic agents in locally advanced or metastatic breast cancer patients pretreated with an anthracycline and a taxane: a systematic review. Eur J Cancer. 2009 Nov;45(16):2749-58.

3. National Institute for Health and Clinical Excellence. NICE clinical guideline 81: Advanced breast cancer: diagnosis and treatment - full guideline. 2009.

4. 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

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

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

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