Comprehensive Monograph on Bexarotene (DB00307): A Selective Retinoid X Receptor Agonist

Executive Summary

Bexarotene is a third-generation, synthetic retinoid, distinguished pharmacologically as a "rexinoid" due to its high and specific affinity for the Retinoid X Receptors (RXRs). It is approved by the U.S. Food and Drug Administration (FDA) and other international regulatory bodies for the treatment of cutaneous manifestations of Cutaneous T-Cell Lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Available in both oral capsule and topical gel formulations, Bexarotene offers a targeted therapeutic approach based on its unique molecular mechanism.

The primary mechanism of action involves the potent agonism of all three RXR subtypes (RXRα, RXRβ, and RXRγ). Upon activation, RXRs form homodimers or heterodimers with other nuclear receptors, functioning as ligand-activated transcription factors that modulate the expression of a wide array of genes controlling cellular proliferation, differentiation, and apoptosis. This activity underlies its antineoplastic effects. Pivotal multinational clinical trials have established the efficacy of oral Bexarotene in advanced-stage, refractory CTCL, with overall response rates of approximately 45%. The topical formulation has demonstrated efficacy in early-stage disease, providing a localized treatment option with a distinct and more favorable safety profile.