Halozyme Therapeutics (HALO) and Eisai Inc. presented a scientific poster entitled, “Pegylated Recombinant Human Hyaluronidase PH20 (PEGPH20) Enhances Efficacy of Eribulin Mesylate (HALAVEN®) in Triple Negative Breast Cancer Xenografts” at the 38th Annual San Antonio Breast Cancer Symposium (SABCS).
The Combination used in the preclinical testing
HALAVEN® (eribulin mesylate) injection, which belongs to Eisai inc., is indicated for patients with metastatic breast cancer who have received at least two prior chemotherapeutic regimens. The previous rior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Halavan® 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.
PEGPH20 (PEGylated recombinant human hyaluronidase) aims at degrading hyaluronan (HA), a chain of natural sugars that accumulate around cancer cells. By degrading HA, PEGPH20 may increase the access of co-administered chemotherapeutic and immunotherapy agents and improve the efficacy of various cancer treatments.
Certain cancers, including pancreatic, breast, colon and prostate, have been shown to accumulate high levels of hyaluronan (HA). Aberrant accumulation of this component of the tumor’s infrastructure supports a protective network or “halo” that surrounds certain tumors. The accumulation of HA along with other matrix components increase tumor interstitial fluid pressure, constricting tumor blood vessels and creating a unique microenvironment for the growth of tumor cells compared to normal cells. These mechanisms generate barriers to drug delivery that inhibit the potential effectiveness of many anti-cancer agents. Dismantling the HA component of the tumor architecture disrupts this unique tumor microenvironment and opens the previously constricted vessels which may increase blood flow to the tumor. This may allow cancer therapies to be more efficiently delivered to their target and thus may be more efficacy. Combining
On Triple Negative Breast Cancer
Results of preclinical model testing of the combination of Halozyme’s PEGPH20 with Eisai drug HALAVEN® showed the potential impact for PEGPH20-mediated hyaluronan (HA) clearance on the concentration of Halaven in the cancer and on the antitumor effects on triple breast cancer therapy.
This is not the first time PEGPH20’s demonstrate capability of eliminating of hyaluronan (HA) from the environment of cancers where HA accumulates and the benefit from this action. This study adds to several validations made already about the value of PEGPH20 in improving the treatments of certain cancers. The current preclinical study revealed important data about the potential for PEGPH20 when used in combination of Halaven in improving the treatment of another difficult to treat cancer, i.e., triple negative breast cancer.
Halozyme and Eisai Co., Ltd., the parent company of Eisai Inc., have signed a clinical collaboration in July 2015 for the initiationg a phase 1b/2 clinical trial to evaluate PEGPH20 plus Halaven in first-line HER2-negative metastatic breast cancer patients with high-HA tumors.
Eisai Inc. is now looking to enrolling patients in clinical trial early next year.
Halozyme is a successful drug design and delivery firm.
Also: The above publication does not necessarily contain information that is consistent with the U.S. prescribing information for HALAVEN® (eribulin mesylate). It is an investigational use and there is no guarantee that this use will become available commercially.
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