A Comprehensive Monograph on Thymalfasin (Thymosin Alpha 1): From Molecular Mechanisms to Clinical and Regulatory Perspectives

Executive Summary

Thymalfasin is a chemically synthesized, 28-amino acid immunomodulatory peptide identical to the endogenous human polypeptide Thymosin Alpha 1 (Tα1). Classified as a biologic drug, its primary therapeutic function is the restoration and enhancement of cell-mediated immunity. The core mechanism of action involves a multifaceted modulation of the immune system, centered on the promotion of T-cell differentiation and maturation. At a molecular level, Thymalfasin acts as an agonist for Toll-like receptors (TLRs), particularly TLR2 and TLR9, on antigen-presenting cells, which initiates a signaling cascade that drives a T-helper 1 (Th1) polarized immune response, characterized by the production of key cytokines such as interferon-gamma (IFN-γ) and interleukin-2 (IL-2).

Clinically, Thymalfasin has achieved widespread use, with regulatory approval in over 35 countries for the treatment of chronic hepatitis B (HBV) and hepatitis C (HCV) infections.[1] Beyond its antiviral indications, it has been extensively investigated and is used in some regions as an adjuvant to chemotherapy in various cancers and as an enhancer of vaccine responses in immunocompromised populations.[4] Its investigational scope continues to expand into areas of acute immune dysregulation, including sepsis and severe COVID-19.