Eisai Co., Ltd., a research-based pharmaceutical company, and Halozyme Therapeutics, Inc., a biotechnology company focused on developing and commercializing novel oncology therapies, have signed a clinical collaboration agreement to evaluate Eisai’s anticancer agent eribulin mesylate ((brand name: Halaven, eribulin) in combination with Halozyme’s investigational new drug PEGPH20 (PEGylated recombinant human hyaluronidase) in first line HER2-negative advanced breast cancer.

Eribulin, a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action, is currently approved for the treatment of advanced breast cancer in approximately 60 countries worldwide.

Structurally, eribulin is a simplified and synthetically produced version 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.

PEGPH20 is an investigational drug administered intravenously that targets the degradation of hyaluronan, a glycosaminoglycan – or chain of natural sugars throughout the body. Hyaluronan accumulates around cancer cells, increasing tumoru interstitial fluid pressure and constricting tumor vasculature, subsequently
inhibiting anticancer agents from reaching cancer cells. By degrading hyaluronan, PEGPH20 increases blood flow to the tumour which may allow cancer therapies to be more efficiently delivered to their target.

Under the agreement, the companies will jointly conduct and share the costs of a phase Ib/II clinical study seeking to determine whether or not the combination therapy of eribulin and PEGPH20 can improve the overall response rate in advanced breast cancer 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 tumour growth inhibition including tumor regression when compared to eribulin alone.

“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 advanced breast cancer,” said Dr. Helen Torley, president and chief executive officer, Halozyme Therapeutics,

Eribulin, a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action, belongs to a class of antineoplastic agents, the halichondrins, which are natural products isolated 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 sequestering tubulin into nonproductive aggregates. Eribulin was first approved as a treatment for breast cancer in the United States in November 2010, and is now approved in nearly 60 countries worldwide, including Japan and countries in the Americas, Europe and Asia. In Japan, eribulin has been approved to treat inoperable or recurrent breast cancer and was launched in the country in July 2011.

Eribulin 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. In July 2015, an application seeking approval for a new indication of soft tissue sarcoma for eribulin was submitted in Japan, the United States and Europe. Meanwhile, eribulin has been designated as an orphan drug for soft-tissue sarcoma in the United States and Japan.