Thymosin alpha 1 (Thymalfasin)

Thymosin alpha 1 (Talpha1; Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn; thymalfasin; CAS 62304-98-7; molecular formula C129H215N33O55; molecular weight 3108.27) is a 28-residue N-acetylated peptide originally isolated from bovine thymus tissue by Allan Goldstein and colleagues at the Albert Einstein College of Medicine in 1977 as a fraction of the broader thymosin fraction 5 immunomodulator. The synthetic peptide was developed by SciClone Pharmaceuticals as Zadaxin and approved in approximately 35 jurisdictions (including most of Asia, Latin America, and parts of Europe) for chronic hepatitis B, chronic hepatitis C (in combination with interferon and ribavirin), and as adjunctive immune-restorative therapy in immunocompromised oncology patients. The compound is not FDA-approved (Phase 3 trials in hepatitis C did not establish independent efficacy at the threshold required by FDA; the agent is approved on different evidence packages in the jurisdictions where it is marketed). Mechanism is multifactorial immunomodulation: enhancement of T cell maturation through Toll-like receptor 9 signaling on dendritic cells, increased Th1 cytokine production, enhanced natural killer cell cytotoxicity, and a more complex effect on regulatory T cell phenotypes that varies with disease context. Routes of administration are subcutaneous twice weekly at 1.6 mg per dose. The compound is distinct from the broader Thymosin Fraction 5 extract and from other thymosin family peptides (Thymosin beta-4, KDC-MN-003; Thymalin; Thymulin; Thymopentin) in being the principal alpha-class thymic immunomodulator with regulatory approval and a substantial randomized clinical trial database. Adverse events are mild and dominated by injection site reactions. Clinical use in COVID-19 and sepsis received attention in 2020 to 2022 with mixed efficacy results in randomized trials.