Eisai Inc. announced that the United States Food and Drug Administration (FDA) has approved HalavenTM (eribulin mesylate) Injection for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included two common chemotherapy treatments, an anthracycline and a taxane, for early or advanced breast cancer. Discovered and developed by Eisai, Halaven is a non-taxane, microtubule dynamics inhibitor that is a synthetic analogue of halichondrin B, a product isolated from the marine sponge Halichondria okadai.
"Many women with metastatic breast cancer see their disease progress after receiving multiple therapies," said Linda Vahdat, M.D., Professor of Medicine, Division of Hematology & Medical Oncology at the Iris Cantor Women's Health Center at New York-Presbyterian Hospital/Weill Cornell Medical Center in New York City. "Now, with the approval of Halaven, we can offer a new option that has been shown to improve survival in women with metastatic disease."
The FDA approval of Halaven is based on results from the pivotal Phase III clinical study EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus Eribulin), which showed that patients treated with Halaven survived a median of 2.5 months longer than patients who received a single-agent therapy chosen by their physician (Treatment of Physician's Choice). Overall survival was 13.12 months with Halaven versus 10.65 months with TPC (p=0.041). In an updated survival analysis, conducted when 77 percent of events had been observed, the result was consistent with the primary analysis.
The most common side effects (incidence ≥ 25 percent) reported by patients receiving Halaven were neutropenia (low white blood cells), anemia (low red blood cells), asthenia/fatigue (weakness/tiredness), alopecia (hair loss), peripheral neuropathy (numbness, tingling or burning in the hands and feet), nausea and constipation. The most common serious side effects reported in patients receiving Halaven were neutropenia with or without fever (four percent and two percent, respectively). Severe weakness/tiredness occurred in 10 percent of patients receiving Halaven. The most common side effect resulting in discontinuation of treatment with Halaven was peripheral neuropathy (five percent).
"The FDA approval of Halaven is significant news for the metastatic breast cancer community in an area of unmet medical need," said Lonnel Coats, President & CEO, Eisai Inc.
"This achievement is consistent with our human health care mission of striving to produce therapies that may help make a difference in the lives of patients and their families."
About the Global Phase III Clinical Study (EMBRACE)
EMBRACE was an open-label, randomized, global, multi-center study designed to compare overall survival in patients treated with Halaven versus a Treatment of Physician's Choice (TPC arm). TPC was defined as any single-agent chemotherapy, hormonal treatment or biologic therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice. The study included 762 patients with metastatic breast cancer who previously had been treated with an average of four prior chemotherapies. The vast majority of patients in the TPC arm received chemotherapy.
"This approval is encouraging news for women with metastatic breast cancer," said Liz Thompson, president of Susan G. Komen for the Cure, the global leader in breast cancer advocacy. "This is a challenging disease and the possibility of improved survival is meaningful to patients and their families."
Halaven is expected to be available in the United States within 10 business days after approval. In addition, Eisai has submitted regulatory applications for approval of eribulin mesylate for the treatment of metastatic breast cancer to regulatory agencies in Japan, the European Union, Switzerland and Singapore.
Important Safety Information about Halaven
Decreased White Blood Cells (Neutropenia)
A doctor will do a blood test to monitor patients' complete blood cells before they receive each dose of HALAVEN, and will monitor patients more often if they develop lower white blood cells. If patients have severe neutropenia lasting longer than seven days or neutropenia with a fever, their next dose of HALAVEN will be delayed and reduced. Severe neutropenia occurred in 57 percent (287/503) of patients who received HALAVEN and lasted more than one week in 12 percent (62/503) of patients. Neutropenia with a fever occurred in five percent (23/503) of patients; two patients died from complications of neutropenia with a fever. Neutropenia with a fever can result in serious infections that could lead to hospitalization or death. Patients should call their healthcare provider immediately if they have any of the following symptoms; fever (100.5 º F), chills, coughing, and burning and pain when they urinate.
Nerve Disorders (Peripheral Neuropathy)
HALAVEN can cause numbness, tingling or burning in the hands and feet (peripheral neuropathy). Patients should be monitored closely for signs of neuropathy. If patients develop severe neuropathy, treatment with HALAVEN should be delayed until the neuropathy improves and the next dose of HALAVEN should be reduced. Severe peripheral neuropathy occurred in eight percent (42/503) of patients who received HALAVEN. Neuropathy lasting more than one year occurred in five percent of patients. Twenty-two percent (109/503) of patients developed a new or worsening neuropathy that had not recovered after an average of 269 days. Peripheral neuropathy was the most common side effect that caused patients to stop taking HALAVEN.
Pregnancy and Nursing
HALAVEN may harm an unborn baby. Patients should avoid becoming pregnant while receiving HALAVEN. Patients should tell their healthcare providers right away if they become pregnant or think they may be pregnant while receiving HALAVEN. With their healthcare providers, patients should decide if they will take HALAVEN or breastfeed. They should not do both.
HALAVEN can cause changes in a patient's heartbeat (called QTc prolongation). This can cause irregular heartbeats that may lead to death. Healthcare providers will decide if patients need heart monitoring (electrocardiogram, or ECG) or blood tests during treatment with HALAVEN to watch for this problem.
Liver and Kidney Problems
A lower dose of HALAVEN should be used if patients have liver and/or kidney problems.
About Metastatic Breast Cancer
Metastatic breast cancer is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body.
In 2010, an estimated 207,000 women will be diagnosed with breast cancer in the United States and 40,000 women will die from the disease. Although statistics on metastatic breast cancer vary, approximately 10 percent of women with breast cancer will have metastatic disease at the time of diagnosis, and an estimated 20 percent of patients with early-stage disease will go on to develop metastatic disease within the next five years. An estimated one in four women with metastatic breast cancer is expected to survive five years.
About Halaven (eribulin mesylate) Injection
Halaven is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane either in the adjuvant or metastatic setting. A non-taxane, microtubule dynamics inhibitor, Halaven is derived from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequesters tubulin into nonproductive aggregates.