HATFIELD, England, July 31, 2015 /PRNewswire/ --

FOR EMEA MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S. JOURNALISTS  

A Type II variation application to extend the indication of Halaven^® (eribulin) was submitted in the European Union for the treatment of patients with inoperable soft tissue sarcoma who have received prior chemotherapy for locally advanced or metastatic disease. Efficacy and safety have been established primarily in patients with leiomyosarcomas and liposarcomas (adipocytic sarcomas), which make up approximately 30% of all soft tissue sarcomas. Similar applications have also been submitted in the US and Japan.

In a pivotal Phase III study, the median overall survival benefit (OS) for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit (HR 0.768; 95% CI 0.618-0.954; p=0.017). Study 309 met its primary objective for OS for use in patients treated with eribulin compared to dacarbazine, the current treatment standard.^[1] These data were presented at an oral session at the American Society of Clinical Oncology (ASCO) in June 2015.

"As clinicians treating soft tissue sarcoma, we have waited for further treatment options which can prolong survival in patients living with these aggressive and hard to treat cancers. Eribulin has a proven overall survival benefit against dacarbazine and I hope that clinicians and patients will not have to wait much longer before being able to access this important new treatment," comments Professor Patrick Schöffski, Head of the Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.

"These submissions confirm Eisai's commitment to helping people who live with rare cancers and represent an exciting step forward for people with soft tissue sarcomas and their families. We know that eribulin has a distinct mode of action and Study 309 was further confirmation of its overall survival benefit in the treatment of complex and aggressive cancers," comments Gary Hendler, President & CEO Eisai EMEA and President, Eisai Oncology Global Business Unit.

Soft tissue sarcomas are cancers that develop from cells in the soft, supporting tissues of the body such as fat, muscle, nerves, fibrous tissues and blood vessels.^[2] Leiomyosarcomas are one of the more common types of sarcoma to develop in adults. They develop from cells called smooth muscle and can start anywhere in the body.^[2] Liposarcomas (adipocytic sarcomas) arise from fat cells and can also occur anywhere in the body. Leiomyosarcomas and liposarcomas make up approximately 30% of all cases of soft tissue sarcomas.^[3]

While soft tissue sarcomas are relatively rare, there remains an unmet medical need for patients who often fail to respond to treatment and therefore have a poor prognosis.^[8]

Study 309 was a randomised, open-label multicentre Phase III study comparing the efficacy and safety of eribulin in 452 patients (aged 18 or over) to dacarbazine. Patients with locally advanced or relapsed metastatic soft tissue sarcomas who had disease progression following standard therapies including an anthracycline and at least one other additional regimen were recruited. Patients in the study had either leiomyosarcomas or liposarcomas.^[4]

In Europe, approximately 29,000 people will be diagnosed with soft tissue sarcomas each year.^[5] The annual incidence of soft tissue sarcomas is approximately 350,000 globally.^[7]

In this study, the most common treatment-emergent adverse events observed in the Halaven arm were fatigue or asthenia, neutropenia, nausea, alopecia, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.^[4]

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 currently 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.^[6]

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.

Notes to Editors  

About Soft Tissue Sarcomas  

Soft tissue sarcoma is a collective term for a diverse group of malignant tumours.

Leiomyosarcomas are one of the more common types of sarcoma to develop in adults. They start from cells in a type of muscle tissue called smooth muscle. Smooth muscles are involuntary muscles that we have no control over. They are found in the walls of muscular organs like the heart and stomach, as well as in the walls of blood vessels throughout the body. This means that leiomyosarcomas can start anywhere in the body. Common places are the walls of the womb (uterus), the trunk of the body, and the arms and legs.^[2]

Liposarcomas (adipocytic sarcomas) arise from fat cells and can occur anywhere in the body. Incidence rates in males are twice as high as those in females.^[7] Leiomyosarcomas and liposarcomas make up approximately 30% of all cases of soft tissue sarcomas.^[3]

Unlike other cancers such as non-small cell lung cancer (NSCLC), soft tissue sarcomas are mostly diagnosed with localised disease, and many are amenable to complete surgical removal, yet relapse rates can be as high as 50 percent.^[8]

Outcomes for patients with advanced disease are poor, with median survival around one year or less. Due to the rarity of these tumours, evidence for prognostic factors is weak and not well understood.^[9]

Global Phase III Clinical Study 309^[4]

The primary endpoint of the study was to compare overall survival between both treatment arms, and the additional endpoints included progression free survival and quality of life.

Patients were aged ≥18 years with advanced high/intermediate grade leiomyosarcoma or dedifferentiated, myxoid, round cell or pleomorphic variants of adipocytic sarcoma (ADI) incurable by surgery and/or radiotherapy were enrolled. Patients had ECOG status ≤2 and had received ≥2 standard systemic treatment regimens including an anthracycline. Patients were randomized 1:1 to eribulin mesilate (1.4 mg/m², IV on D1 and D8) or dacarbazine (850-1200 mg/m², IV on D1) every 21 days until disease progression.

Overall, 452 patients (67% female; 79% <65 years) were randomized (228 eribulin; 224 dacarbazine). Median OS for eribulin and dacarbazine was 13.5 and 11.5 months, respectively (HR=0.768, 95% CI 0.618-0.954; P=0.017). PFS was 2.6 months in both arms (HR=0.877, 95% CI 0.710-1.085; P=0.229). PFS rate at week 12 was 33% and 29% for eribulin and dacarbazine, respectively. Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. In this study, the most common adverse events observed in the eribulin arm were neutropenia, fatigue, nausea, alopecia and constipation, which is consistent with the known profile of eribulin.

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 EMEA in Oncology  

Eisai is committed to developing and delivering highly beneficial new treatments to help improve the lives of people with oncology. The development of cancer therapies is a major strategic area for Eisai in Europe, the Middle East, Africa, Russia and Oceania (EMEA).

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.

References  

1. Schöffski P et al. Randomized, open-label, multicenter, phase 3 study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI). American Society of Clinical Oncology annual meeting 2015; Abstract #LBA10502
2. Macmillan. What are soft tissue sarcomas? http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Softtissuesarcomas/Aboutsofttissuesarcomas/Softtissuesarcomas.aspx . Accessed: July 2015
3. Cancer Research UK, Soft Tissue Sarcoma Incidence Statistics: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/soft-tissue-sarcoma/incidence/ Accessed: July 2015
4. Clinicaltrials.gov https://clinicaltrials.gov/ct2/show/NCT01327885?term=halaven+soft+tissue+sarcoma&rank=2 Accessed: July 2015
5. ESMO Guidance: http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Accessed: July 2015
6. 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: July 2015
7. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/adult-soft-tissue-sarcoma/HealthProfessional/page1 . Accessed: July 2015
8. R. Pollock. Soft Tissue Sarcomas: A Volume in the American Cancer Society Atlas of Clinical Oncology Series. 2012
9. Fletcher et al. World Health Organization Classification of Tumours of Soft Tissue and Bone (4th Edition). Lyon: IARC Press, 2013.

Date of preparation: July 2015

Job code: Halaven-UK0437

SOURCE Eisai