Enzon Pharmaceuticals, Inc. (Nasdaq: ENZN) today announced the Investigational New Drug (IND) approval by the US Food and Drug Administration (FDA) and plan to commence enrollment into a Phase 1a/1b study shortly. The study will evaluate the safety and tolerability of EZN-4176, the company’s novel androgen receptor (AR) mRNA antagonist, for the treatment of patients with castration-resistant prostate cancer (CRPC). Unlike other novel agents for CRPC that inhibits androgen production or receptor activation, EZN-4176 is unique in its ability to eliminate androgen receptor.
The open-label, Phase 1a/1b, non-randomized study will enroll adult patients with CRPC, who will receive EZN-4176 as a weekly, one-hour intravenous infusion in four-week treatment cycles. The study will have two phases: Phase 1a will determine the maximum tolerated dose, after which pharmacokinetic and pharmacodynamic studies will be conducted at one or more dose levels in Phase 1b to determine the recommended Phase 2 dose.
Enzon’s initiation of this study follows the presentation of preclinical data at the 2010 EORTC-NCI-AACR meeting demonstrating potent anti-tumor activity for EZN-4176, both alone and in combination with MDV-3100, a novel AR antagonist that is currently in Phase 3 testing.
Prostate cancer is a common cause of cancer-related deaths among men in the United States, a fact that underscores the need for new treatment options, particularly for late-stage disease. In the preclinical setting, EZN-4176 exhibited robust tumor-growth inhibition that correlated with down-modulation of the AR, and consequently inhibition of transcription activity.
Ivan Horak, MD, Enzon’s president of research and development and chief scientific officer, commented, “The initiation of this study marks an important step in the advancement of Enzon’s third-generation mRNA antagonists, which are based on proprietary Locked Nucleic Acid technology. We believe that the enhanced stability, potency and affinity of these compounds will translate to meaningful improvements in the treatment of CRPC and other cancers with high unmet medical need.”