Eisai Inc. announced today that its parent company Eisai Co., Ltd. (Headquarters: Tokyo, President and CEO: Haruo Naito, “Eisai”) and Halozyme Therapeutics, Inc. (Headquarters: San Diego, California, President and CEO: Dr. Helen Torley, “NASDAQ: HALO”) have signed a clinical collaboration agreement to evaluate Eisai’s agent eribulin mesylate (brand name: Halaven®, “eribulin”) in combination with Halozyme’s investigational drug PEGPH20 (PEGylated recombinant human hyaluronidase) in first line HER2-negative metastatic breast cancer. The companies will jointly share the costs of a phase 1b/2 clinical trial to assess whether or not eribulin, in combination with PEGPH20, can improve overall response rate (ORR) — the proportion of women that have a predefined reduction in tumor burden — as compared with eribulin alone as a therapy in women with advanced breast cancer.
PEGPH20 (PEGylated recombinant human hyaluronidase) is an investigational drug administered intravenously that targets the degradation of hyaluronan, a glycosaminoglycan – or chain of natural sugars throughout the body – that can accumulate around cancer cells to inhibit other therapies. The collaborative study will seek to determine whether or not the combination therapy of eribulin and PEGPH20 can improve the overall response rate in patients with high levels of hyaluronan. In hyaluronan-rich triple-negative breast preclinical animal models, the addition of PEGPH20 to eribulin showed a significantly higher tumor growth inhibition and overall tumor regression when compared to eribulin alone.
Eribulin is not indicated for first-line therapy for patients with HER2-negative metastatic breast cancer.
Eribulin is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally, eribulin is a modified and synthetically produced analog of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibition of the growth phase of microtubule dynamics which prevents cell division.
“This is a very important collaboration, one that speaks to our continued commitment to address the unmet medical needs of patients with advanced breast cancer,” said RuiRong Yuan, MD, Vice President and Chief Medical Officer, Eisai Global Oncology. “We look forward to enrolling patients in the clinical trial and assessing the results.”
“This agreement marks the first clinical collaboration agreement for Halozyme and extends the study of PEGPH20 to a substantially wider population of patients with a partner that is a clear leader in the treatment of metastatic breast cancer,” said Dr. Helen Torley, President and CEO, Halozyme Therapeutics.
The information discussed in this release presents an investigational use for an FDA-approved product (eribulin). It is not intended to convey conclusions about efficacy or safety. There is no guarantee that the investigational use of the combination of eribulin and PEGPH20 will successfully gain FDA approval.
About Advanced Breast Cancer
Advanced or metastatic breast cancer is a very difficult condition to treat and only 25.9% of women will survive beyond five years.
PEGPH20 is currently under development in combination with chemotherapies for the treatment of metastatic pancreatic cancer and non-small cell lung cancer with plans for it to be studied in combination with an immunotherapy agent later this year.
About Eribulin Mesylate Injection (Available as Halaven®)
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
- 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 3) 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
- 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
- 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 atwww.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 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.
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 realize our hhc philosophy by delivering innovative products in various 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 visitwww.eisai.com.
Halozyme Therapeutics is a biotechnology company focused on developing and commercializing novel oncology therapies that target the tumor microenvironment. Halozyme’s lead proprietary program, an investigational drug PEGPH20, applies a unique approach to targeting solid tumors, allowing increased access of co-administered cancer drug therapies to the tumor. PEGPH20 is currently in development for metastatic pancreatic cancer and non-small cell lung cancer and has potential across additional cancers in combination with different types of therapies. In addition to its proprietary product portfolio, Halozyme has established value-driving partnerships with leading pharmaceutical companies including Roche, Pfizer, Janssen, Baxalta and AbbVie for its drug delivery platform, ENHANZE™, which enables biologics and small molecule compounds that are currently administered intravenously to be delivered subcutaneously. Halozyme is headquartered in San Diego. For more information, visit halozyme.com.