Phase 3 Trial Investigating Eribulin in Patients with Advanced Soft Tissue Sarcoma Demonstrated Improved Overall Survival

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• USA - English

WOODCLIFF LAKE, N.J., May 30, 2015 /PRNewswire/ -- Eisai Inc. announced today the results of its Phase 3 trial (Study 309), which showed that eribulin met the study's primary endpoint evaluating overall survival in patients who had advanced leiomyosarcoma (LMS) or adipocytic sarcoma (ADI), two types of advanced soft tissue sarcoma. These data will be presented at the 51^st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago as part of the ASCO press conference on Saturday, May 30, and also in an oral session on Monday, June 1 at 3:48 p.m. CT (Abstract No. LBA10502).

"For patients with advanced soft tissue sarcoma, outcomes are often poor and there are limited treatment options," said Patrick Schöffski, MD, MPH, Department of General Medical Oncology, University Hospitals Leuven, Belgium. "These results are important in a disease where so few treatment options exist."

Data from Study 309 demonstrated patients treated with eribulin (n=228) experienced a median overall survival of 13.5 months compared to 11.5 months for those treated with dacarbazine (n=224) (HR 0.768; 95% CI 0.618-0.954; p=0.017). The secondary endpoints of the Phase 3 trial (Study 309) included progression-free rate (PFR) at week 12 and progression-free survival (PFS). While there was a numerical difference in PFR at week 12 between the eribulin and dacarbazine arms (33% vs 29%), this was not statistically significant. Median PFS was 2.6 months in both arms.

Safety was an additional secondary endpoint of Study 309. Data demonstrated eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. In this study, the most frequent treatment-emergent adverse events in the eribulin arm were neutropenia, fatigue, nausea, alopecia and constipation.

Study 309 was a randomized, open-label, multicenter trial of eribulin mesylate 1.4mg/m² administered intravenously (IV) on days one and eight of a 21-day cycle versus dacarbazine IV on day one, every 21 days (dose range of 850 mg/m² to 1,200 mg/m²) to patients (n=452) with locally advanced or recurrent and/or metastatic LMS or ADI who had disease progression following two standard therapies, one of which must have been an anthracycline (unless contraindicated).

"Study 309 represents the first investigational Phase 3 trial in patients with soft tissue sarcoma to demonstrate an overall survival benefit compared with an active agent," said Kenichi Nomoto, Ph.D., President, Oncology Product Creation Unit at Eisai Inc. "We are proud of our ongoing research efforts that may expand the value of existing therapies to address the unmet medical needs of patients, especially those with rare and orphan cancers, across the oncology spectrum."

The information discussed in this release presents an investigational use for an FDA-approved product. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that the investigational use of this FDA-approved product will successfully complete clinical development or gain FDA approval.

About Soft Tissue Sarcoma
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. The annual incidence of soft tissue sarcoma is approximately 30 cases per million of the population – equivalent to less than 1% of all malignant tumors.  Soft tissue sarcomas are mostly diagnosed in early-stage or localized disease, and many patients are amenable to complete surgical removal, yet relapse rates can be as high as 50% and outcomes for patients with advanced disease are poor, with median survival around 1 year or less. 

About Eribulin Mesylate Injection (Available as Halaven^®) 
Eribulin is not indicated for patients with advanced soft tissue sarcoma.

Eribulin mesylate injection is indicated for patients with metastatic breast cancer who have received at least two chemotherapeutic regimens for the treatment of metastatic breast cancer. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First in the halichondrin class, eribulin is a microtubule dynamics inhibitor with a distinct binding profile. Based on in vitro studies, eribulin exerts its effect via a tubulin-based antimitotic mechanism ultimately leading to apoptotic cell death after prolonged and irreversible mitotic blockage.

Important Safety Information

Neutropenia

• Monitor complete blood counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days
• Severe neutropenia (ANC <500/mm³) lasting more than 1 week occurred in 12% (62/503) of patients. Patients with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels
• Grade 3 and Grade 4 neutropenia occurred in 28% and 29%, respectively, of patients who received eribulin. Febrile neutropenia occurred in 5% of patients and two patients (0.4%) died from complications

Peripheral Neuropathy

• Patients should be monitored closely for signs of peripheral motor and sensory neuropathy
• Grade 3 peripheral neuropathy occurred in 8% of patients, and Grade 4 in 0.4% of patients who received eribulin. Delay administration of eribulin until resolution to Grade 2 or less
• Neuropathy lasting more than 1 year occurred in 5% of patients. Twenty-two percent of patients developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days)
• Peripheral neuropathy (5%) was the most common adverse reaction resulting in discontinuation

Pregnancy Category D

• Eribulin is expected to cause fetal harm when administered to a pregnant woman and patients should be advised of these risks

QT Prolongation

• In an uncontrolled ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no prolongation on Day 1. ECG monitoring is recommended for patients with congestive heart failure; bradyarrhythmias; concomitant use of drugs that prolong QT interval, including Class Ia and III antiarrhythmics; and electrolyte abnormalities
• Correct hypokalemia or hypomagnesemia prior to initiating eribulin and monitor electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome

Hepatic and Renal Impairment

• For patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic and/or moderate or severe (CrCl 15-49 mL/min) renal impairment, a reduction in starting dose is recommended

Most Common Adverse Reactions

• Most common adverse reactions (≥25%) reported in patients receiving eribulin were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%)
• The most common serious adverse reactions reported in patients receiving eribulin were febrile neutropenia (4%) and neutropenia (2%)

For more information about eribulin, click here for the full Prescribing Information.

About Eisai Inc.
At Eisai Inc., human health care is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care (Alzheimer's disease, epilepsy and metabolic disorders). To learn more about Eisai Inc., please visit us at www.eisai.com/US.

Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey, North Carolina and Pennsylvania, as well as a global demand chain organization that includes manufacturing facilities in Maryland and North Carolina. Eisai's global areas of R&D focus include neuroscience; oncology; metabolic disorders; vascular, inflammatory and immunological reaction; and antibody-based programs.

SOURCE Eisai Inc.

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