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ºÚÁÏÍø., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “ºÚÁÏÍø”) announced today that the results of a Phase Ⅲ clinical study (Study 309) of its in-house discovered and developed anticancer agent Halaven® (eribulin mesylate) in patients with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma)¹ have been published in the online version of The Lancet, a leading medical journal that is highly regarded worldwide.

Halaven is the first and only single agent systemic therapy to demonstrate an improvement in overall survival (OS) in people previously treated for soft tissue sarcomas in a randomized controlled trial. In Study 309, which examined the efficacy and safety of Halaven versus dacarbazine in patients with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) who had disease progression following standard therapies (including an anthracycline and at least one other additional regimen), Halaven demonstrated a statistically significant extension in the study's primary endpoint of OS over the comparator treatment dacarbazine (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months; Hazard Ratio (HR) 0.77 [95% CI=0.62-0.95], p=0.0169).
In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 25%) in patients treated with Halaven were fatigue, neutropenia, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia, which was consistent with the known side-effect profile of Halaven.

Halaven is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.² Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate.³ It was first approved for the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved for use in the treatment of breast cancer in approximately 60 countries including Japan and countries in Europe, the Americas and Asia.

In January 2016, Halaven was approved in the United States for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen, and applications seeking approval for use in the treatment of soft tissue sarcoma are currently under review in Japan and Europe. Halaven has been designated as an orphan drug for the treatment of soft tissue sarcoma in the United States and Japan.

ºÚÁÏÍø remains committed to providing further clinical evidence for Halaven aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

Halaven is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Structurally Halaven is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Halaven is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.² Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate.³
Halaven was first approved as a treatment in the United States in November 2010 for patients with metastatic breast cancer who have received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Halaven is currently approved for use in the treatment of breast cancer in approximately 60 countries worldwide, including Japan and countries in Europe, Americas and Asia. In Japan, Halaven has been approved to treat inoperable or recurrent breast cancer and was launched in the country in July 2011. Halaven has also been approved in countries in Europe and Asia indicated as a treatment for patients 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.
Regarding soft tissue sarcoma, Halaven has been approved in the United States for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen, and applications seeking approval for use in the treatment of soft tissue sarcoma have been submitted in Japan and Europe. Halaven has been designated as an orphan drug for the treatment of soft-tissue sarcoma in the United States and Japan.

Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (fat, muscle, nerves, fibrous tissues and blood vessels) in the body. As the structures where the tumors originate are diverse, there are various types of soft tissue sarcoma, and the most common types include leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. Approximately 12,000 patients in the United States and 29,000 patients in Europe are diagnosed with soft tissue sarcoma each year. According to a patient survey conducted by Japan's Ministry of Health, Labour and Welfare, there are approximately 4,000 patients with soft tissue sarcoma in Japan. While treatment of soft tissue sarcoma is focused on curative surgery, if the degree of malignancy is high, treatment then becomes a combination of chemotherapy and radiation therapy. As outcomes are poor for patients with advanced disease, it remains a disease with significant unmet medical need.

Conducted primarily in Europe and the United States, Study 309 was a multicenter, open-label, randomized Phase Ⅲ study comparing the efficacy and safety of Halaven versus dacarbazine in 452 patients (aged 18 or over) with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen. Patients received either Halaven (1.4 mg/m² administered intravenously on Day 1 and Day 8) or dacarbazine (850–1200 mg/m² administered intravenously on Day 1) every 21 days until disease progression.
From the results for the study, Halaven demonstrated a statistically significant extension in the study's primary endpoint of overall survival (OS) over the comparator treatment dacarbazine (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months; Hazard Ratio (HR) 0.77 [95% CI=0.62-0.95], p=0.0169). Furthermore, in the study's secondary endpoint of progression-free rate at 12 weeks (PFR_12wks), while there was a numerical difference in PFR12wks between the Halaven and dacarbazine arms (33% vs 29%), this was not statistically significant. Median progression-free survival was 2.6 months in both arms.
The most common adverse reactions (incidence greater than or equal to 25%) in patients treated with Halaven were fatigue, neutropenia, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia, which was consistent with the known side-effect profile of Halaven.

First published in 1823 and with a history spanning over 180 years, The Lancet is an influential medical journal that is highly regarded worldwide.