HALAVEN™ (ERIBULIN) RECEIVES EUROPEAN COMMISSION APPROVAL FOR ADVANCED BREAST CANCER

EMBRACE was an open-label, randomized, global, multi-center, parallel two-arm study designed to compare overall survival in patients treated with Halaven™ 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. (overall survival for patients treated with Halaven™ when compared with TPC, median OS 13.1 and 10.6 months respectively; HR 0.81; p=0.041)¹⁾

An updated analysis of overall survival (not protocol prespecified) of EMBRACE study was performed under the request of European and US regulatory authorities. The results confirmed the significant increase in overall survival for Halaven™ compared with TPC, and no change in safety profile, which was presented in San Antonio Cancer Symposium in 2010. (median OS 13.2 and 10.5 months respectively; HR 0.81; p=0.014)²⁾

The most common adverse reactions (incidence greater than or equal to 25%) among patients treated with Halaven™ were asthenia (fatigue), neutropenia, anemia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms, legs and other parts of the body), nausea and constipation. The most common serious side effects reported in patients receiving Halaven™ were neutropenia with or without fever (4% and 2%, respectively). The most common adverse reaction resulting in discontinuation of treatment with Halaven™ was peripheral neuropathy (5%).

Halaven™ is a non-taxane, microtubule dynamics inhibitor, 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 sequestering tubulin into nonproductive aggregates.

Synthesizing Halaven™ is an extremely difficult and complex process, involving some 62 steps to achieve total synthesis. Halaven™ has a molecular weight of 826, including 19 chiral carbons, which means the theoretical number of stereoisomers is 2¹⁹, or a possible 524,000, making stereocontrol potentially extremely difficult. However, due to the advanced technological capabilities and strategies of the Eisai discovery and process research teams, it was possible to stereoselectively control all synthetic reactions and commercially synthesize Halaven™.

Eisai is currently conducting late stage clinical trials investigating the potential of Halaven™ as a single-agent therapy in the treatment of other types of cancer such as breast cancer with fewer prior treatments, non-small cell lung cancer, sarcoma, and prostate cancer with the aim of expanding the range of indications for which the agent can be used to treat.

Worldwide, more than one million women a year are diagnosed with breast cancer, including 421,000 women in Europe. Approximately 30 percent of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent or metastatic disease, and while around 9 out of 10 of women diagnosed with early stage breast cancer survive beyond five years, this drops to around 1 in 10 among women first diagnosed with MBC. Most MBC patients have a limited survival time of approximately 18 to 24 months.