Topline Results of Phase 3 Trial Show Eribulin Mesylate Injection Meets Primary Endpoint of Overall Survival in Advanced Soft Tissue Sarcoma

Eisai Demonstrates Commitment to Patients with Rare Cancers

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Feb 25, 2015, 07:55 ET

WOODCLIFF LAKE, N.J., Feb. 25, 2015 /PRNewswire/ -- Eisai Inc. today announced that eribulin met the primary endpoint in its Phase 3 trial (Study 309), demonstrating a statistically significant improvement in overall survival (OS) in patients with advanced soft tissue sarcomas versus the comparator treatment dacarbazine. Eisai plans to present these data at an upcoming medical meeting.

This is the second Phase 3 trial in which eribulin, as a single agent, demonstrated an overall survival benefit in a distinct solid tumor type (metastatic breast cancer and advanced soft tissue sarcomas) following two prior treatment regimens in the advanced setting. Eribulin is an investigational product not currently FDA approved for soft tissue sarcoma. It is an FDA-approved treatment 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.

"The study results show the potential role of eribulin for the treatment of patients with soft tissue sarcoma, where a need exists for additional treatment options," said Kenichi Nomoto, Ph.D., President, Oncology Product Creation Unit, Eisai Inc. "We are excited about the results of this study, which reinforces our continued commitment to discovering potential new treatment options for people with rare and orphan cancers."

Eribulin was granted orphan drug designation by the FDA as an investigational compound for the treatment of soft tissue sarcoma. Approximately 12,000 cases of soft tissue sarcoma will be diagnosed in the United States this year and 4,700 Americans are expected to die of the disease. While many patients with soft tissue sarcoma are diagnosed early in their disease and are curable with surgery, outcomes for patients with advanced or metastatic disease are poor and median survival is around one year or less.

Study 309 was a randomized, open-label multicenter Phase 3 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 adipocytic sarcoma or leiomyosarcoma who had disease progression following two standard therapies which must have included an anthracycline and at least one additional regimen after anthracycline failure. The primary endpoint of the study was to compare OS between both treatment arms. In this study, the most common adverse events (AEs) observed in the eribulin arm were neutropenia, fatigue, nausea, alopecia and constipation.

Based on the results of Study 309, Eisai intends to submit applications during Fiscal Year 2015 to regulatory authorities in multiple regions, including the United States, Japan and Europe, seeking an expansion of the indication for eribulin to include soft tissue sarcoma.

This research demonstrates Eisai's commitment to oncology and helping to address the unmet medical needs of patients, especially those with rare and orphan cancers. 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.

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. 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. Because of the rarity of these tumors, evidence for prognostic factors is weak and not well understood.

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

Eribulin 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 Product 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.