ANX-514 (docetaxel for injectable emulsion)

ANX-514 is a novel, detergent-free emulsion formulation of docetaxel, an intravenously-injected chemotherapy drug commonly used to treat solid tumors.

Taxotere®, a branded formulation of docetaxel, is approved to treat breast, non-small cell lung, prostate, gastric, and head and neck cancers.

The ANX-514 formulation was designed to have efficacy comparable to Taxotere without the non-active, toxic components found in Taxotere and without the corticosteroid premedication regimen required with Taxotere.

Background & Potential Benefits

The Taxotere formulation has certain limitations; principally, toxicity associated with its excipient, polysorbate 80, and the corticosteroid premedication regimen intended to ameliorate Taxotere-related toxicities. Docetaxel, the active ingredient in Taxotere, is lipophilic and practically insoluble in water. Taxotere and currently available non-Taxotere formulations of docetaxel use detergents to solubilize docetaxel.

ANX-514 was designed to have clinically comparable release of docetaxel relative to Taxotere while eliminating the presence of polysorbate 80 and ethanol, both of which are used to solubilize docetaxel in the Taxotere formulation. The ANX-514 formulation solubilizes docetaxel using oil droplets comprised of a combination of non-toxic excipients. Docetaxel is contained within these oil droplets and can be administered intravenously without using detergents as pharmaceutical vehicles. Once in central circulation, the emulsion is metabolized rapidly, leaving chemically-identical active ingredient to exert its cytotoxic effect. The rate and extent of absorption of docetaxel from ANX-514 was designed to be comparable to that of Taxotere, resulting in similar clinical outcomes attributable to the active ingredient.

Due to the absence of polysorbate 80 and ethanol in the ANX-514 formulation, ANX-514 may demonstrate an improved safety profile relative to Taxotere and other formulations of docetaxel that use detergents as solubilizing agents or contain alcohol. ANX-514 may reduce the incidence and severity of hypersensitivity reactions and delay the onset of fluid retention. In addition, dexamethasone premedication intended to address polysorbate 80-mediated hypersensitivity reactions and fluid retention may be unnecessary with detergent-free ANX-514. Avoiding the high-dose corticosteroid premedication required for treatment with Taxotere and other available docetaxel formulations could significantly benefit cancer patients, particularly diabetics or pre-diabetics (those with impaired fasting glucose), who we estimate constitute one-third of the patients who historically received Taxotere. Dexamethasone and other glucocorticoids are associated with development of hyperglycemia.

2007 American Association for Cancer Research (AACR) Annual Meeting Poster Presentation (Click here to view)

“A novel emulsion formulation of docetaxel eliminates hypersensitivity reactions without impacting pharmacokinetics of antitumor activity,” M. J. Cantwell, J. M. Robbins and A.X. Chen, Los Angeles, CA, October, 2007.