Thymosin Alpha-1 vs Thymosin Beta-4

How Thymosin Alpha-1 and Thymosin Beta-4 differ

Thymosin Alpha-1 and Thymosin Beta-4 are not the same molecule: they share part of a name and little else. Thymosin Alpha-1 is a synthetic 28-residue peptide whose sequence matches residues 2 to 29 of prothymosin alpha. Its international nonproprietary name is thymalfasin. Thymosin Beta-4 is a 43-residue peptide found across most human tissues. The material supplied is made in the laboratory. Thymosin Alpha-1 comes from a different precursor gene, yet Thymosin Beta-4 is routinely confused with it.

Evidence for Thymosin Beta-4 does not transfer to Thymosin Alpha-1. In the literature reviewed for Thymosin Alpha-1, the human record includes randomized trials. The largest, of 1,106 participants, in one indication, found no significant difference overall on the measures reported for it.^[2] In that trial, no safety outcome differed from placebo overall, and one prespecified subgroup showed higher mortality on the drug than on placebo, a hypothesis-generating finding.^[2] FDA's review also cites reports of fatal immune hemolytic anemia and engraftment failure in transplant recipients; such reports cannot show cause or frequency.^[5] Two registered trials are listed as completed but unpublished.^[3]

Thymosin Beta-4 has a two-decade record of human clinical development, and most of what has read out has failed. Three later trials in one indication randomized 1,618 patients between them, and none of the three has a peer-reviewed publication. The literature reviewed for Thymosin Beta-4 reports no serious safety finding from its published human studies.

A medicine containing thymalfasin holds a national marketing authorization in Italy, in one indication.^[4] Thymalfasin is the active ingredient of a medicine authorized in Italy. The material supplied here is a research-grade preparation, is not that medicine, and holds no marketing authorization. The Italian authorization belongs to thymalfasin alone and is not an approval of Thymosin Beta-4. The FDA has approved no drug product containing thymalfasin.^[5] No marketing application for Thymosin Beta-4 has ever been submitted to the FDA, in any formulation.

Have Thymosin Alpha-1 and Thymosin Beta-4 been compared directly?

Between 1981 and 2007, fourteen studies in the literature reviewed for Thymosin Beta-4 each applied both Thymosin Alpha-1 and Thymosin Beta-4 in the same experimental system. Seven used human cells in vitro, among them blood cells and sperm cells.^{[10][11][12][13][14][15][16]} Four used rat cells in vitro, among them adrenal and spleen cells.^{[17][18][19][20]} One used rat hypothalamic tissue, superfused outside the body.^[7] Two more included work in vivo. One exposed mouse macrophages to both peptides in culture, then transferred cells from those cultures into mice.^[8] The other applied both peptides to the chick chorioallantoic membrane.^[21] One of the human-cell studies also tested both peptides in mice.^[15] Results are reported for each compound in each paper. For two further papers, the abstracts do not establish that both peptides were applied.^[22][23]