Halaven® (Eribulin) Receives Positive CHMP Opinion in Advanced Liposarcoma Following Significant Phase III Data

HATFIELD, England, April 4, 2016 /PRNewswire/ --

FOR EU MEDIA ONLY: NOT FOR SWISS AND AUSTRIAN MEDIA 

Variation to extend indication of eribulin for treatment of adult patients with unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease^[1] 

Positive opinion for licence extension to Halaven^® (eribulin) from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is based on pivotal Phase III data which show a median 7.2 month increase in overall survival compared to dacarbazine (15.6 months versus 8.4 months, HR = 0.511; 95% CI 0.346-0.753; P=0.0006) for people with unresectable advanced or metastatic liposarcomas.^[1] Eribulin is the first and only single agent therapy to show a significant survival advantage in this type of soft tissue sarcoma.^[2]

"Eribulin has been shown to extend the lives of adults with specific types of progressive soft tissue sarcoma, which are rare and have a high rate of mortality. This positive opinion is welcomed by sarcoma specialists in Europe, who have few options to treat these patients. These data are a clinically meaningful result given the significant unmet need. This is the first and only time that we have been able to demonstrate an overall survival benefit in soft tissue sarcoma in a large Phase III trial, which mirrors the results for eribulin in advanced breast cancer," said Patrick Schöffski, Head of the Department of General Medical Oncology, University Hospitals Leuven, Belgium.

Eribulin shows a median overall survival improvement of 2.6 months (13.5 months versus 11.5 months) in patients with leiomyosarcomas or liposarcomas (L-type soft tissue sarcomas) when compared with dacarbazine, an active treatment option (HR=0.768, 95% CI 0.618-0.954; P=0.017).^[2] There were no unexpected or new safety findings; the toxicity profile is consistent with the known safety profile of eribulin.^[2] The pivotal study results were published in The Lancet, February 2016.^[2]

Eribulin is a microtubule-dynamics inhibitor, structurally modified analogue of halichondrin B, originally isolated from the marine sponge Halichondria okadai. Its mode of action is distinct from other tubulin inhibitors and involves binding to specific sites on the growing positive ends of microtubules to inhibit their growth. Eribulin also induces vascular remodelling, suppresses migration and invasion of cancer cells, and reverses the epithelial-to-mesenchymal transition in many cancer cell lines.

Only 50% of people with soft tissue sarcomas are expected to live five years.^[3] 29,000 people are diagnosed with soft tissue sarcomas each year, approximately 1% of all cancers diagnosed in Europe.^[4] Liposarcomas (adipocytic sarcomas) originate in fat cells and can occur anywhere in the body.^[5]

"For the first time, people with liposarcoma, a rare and difficult to treat cancer, have an option that can significantly extend their lives. This is the second form of cancer in which eribulin has demonstrated an overall survival cancer benefit, and we remain committed to developing eribulin's potential for people with cancer, their family and carers," comments Gary Hendler, President and Commercial Director, Eisai Global Oncology Business Unit and Chairman & CEO, Eisai EMEA.

In January 2016 the Food and Drug Administration (FDA) approved eribulin for the treatment of people in the US with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen. Licence was granted in Japan to extend the indication of eribulin to treat patients with soft tissue sarcomas in February 2016.

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  

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 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]

About Soft Tissue Sarcomas 

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

Leiomyosarcomas and liposarcomas make up around 30% of all cases of soft tissue sarcomas^[7] and develop from cells in the tissues that surround the body such as fat, muscle, nerves, fibrous tissues and blood.^[4] Leiomyosarcomas form from cells called smooth muscle and can start anywhere in the body.^[4]

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^[2]

Study 309 is a randomised, open-label multicentre Phase III study comparing the efficacy and safety of eribulin mesilate in 452 patients (aged 18 or over).^[2]

The primary endpoint of the study was to compare overall survival between patients treated with eribulin mesilate 1.4 mg/m² (equivalent to eribulin 1.23mg/m^[2]) intravenously on days 1 and 8 and those treated with dacarbazine (850 mg/m², 1000 mg/m², or 1200 mg/m² [dose dependent on centre and clinician] intravenously on day 1). The additional endpoints included progression free survival and quality of life.^[2]

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.^[2] Patients were randomized 1:1 to eribulin mesilate (1.4 mg/m^[2], IV on D1 and D8) or dacarbazine (850-1200 mg/m2, IV on D1) every 21 days until disease progression.^[2]

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.^[2] 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.^[2]

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.  

References  

1. European Medicines Agency. Summary of Opinion (post authorisation) Halaven, eribulin April 2016. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/002084/WC500203965.pdf

2. Schöffski P et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2016

3. National Cancer Institute - http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-survival-rates

4. ESMO Guidance. Available at: http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html  Accessed: November 2015

5. Macmillan. What are soft tissue sarcomas? Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Softtissuesarcomas/Aboutsofttissuesarcomas/Softtissuesarcomas.aspx .  Accessed: November 2015

6. SPC Halaven (updated November 2015). Available at: http://www.medicines.org.uk/emc/medicine/24382  Accessed: December 2015

7. Cancer Research UK, Soft Tissue Sarcoma Incidence Statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/soft-tissue-sarcoma/incidence/    Accessed: November 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