Thymosin alpha-1 (generic name thymalfasin, marketed as Zadaxin) holds regulatory approval in more than 35 countries for hepatitis B and C, but not from the FDA. This page describes what its trials found — including where they found nothing.
Overview
Thymosin alpha-1's established use is as an adjunct in chronic viral hepatitis, where it is approved in dozens of countries. Its proposed benefit is immune modulation rather than stimulation: a 28-amino-acid fragment of thymic protein that appears to normalise T-cell and antigen-presenting-cell activity rather than push it in one direction.
Two things distinguish this peptide from most immune-support compounds sold alongside it. First, it has genuine approvals and decades of clinical trials. Second — and this cuts the other way — its single largest and most rigorous trial, published in the BMJ in 2025, found no benefit for its most prominent investigational use. Both facts belong in any honest summary.
Hepatitis — the approved indication
The hepatitis B evidence has an unusual shape. A meta-analysis of four randomised trials comparing thymosin alpha-1 with interferon alpha in 199 patients found that during treatment interferon looked better — odds ratios around 0.54 to 0.62 favouring interferon at six months — but that at six months of follow-up the pattern reversed, with odds ratios of 3.71 for virological response and 2.69 for complete response favouring thymosin alpha-1 (Antiviral Research 2008; PMID 18078676). The authors describe the benefit as accumulating gradually after therapy ends rather than during it.
A larger meta-analysis of seven randomised trials in 1,144 patients with HBV-related cirrhosis compared entecavir plus thymosin alpha-1 against entecavir alone. At 24 weeks the combination looked clearly better — HBV DNA undetectability RR 1.91 (95% CI 1.56–2.35), HBeAg loss RR 2.05 (95% CI 1.62–2.60) — but by 48 to 52 weeks there was no significant difference between the groups. Adverse events were actually fewer with the combination (RR 0.48, 95% CI 0.24–0.95). All seven trials came from mainland China (BMC Gastroenterology 2020; PMID 33076834).
The honest reading is that thymosin alpha-1 accelerates early virological response as an add-on, with the advantage narrowing over a year, in a literature concentrated in one country.
Sepsis — the largest trial, and a null result
Thymosin alpha-1 has long been proposed for sepsis on the theory that sepsis-induced immune paralysis is exactly what an immune normaliser should correct. TESTS tested that directly: a multicentre, double-blind, randomised, placebo-controlled phase 3 trial with 1,089 adults in the modified intention-to-treat analysis, given subcutaneous thymosin alpha-1 or placebo every 12 hours for seven days.
Twenty-eight-day all-cause mortality was 23.4% (127 of 542) with thymosin alpha-1 and 24.1% (132 of 547) with placebo — a hazard ratio of 0.99 (95% CI 0.77–1.27; p=0.93). The authors concluded there was no clear evidence of a mortality benefit (BMJ 2025; PMID 39814420). Exploratory subgroup signals by age and diabetes status were flagged as hypothesis-generating, which is the appropriate weight to give them.
This is the best-powered study the compound has, and it is negative. That does not invalidate the hepatitis approvals, but it does show what happens when a plausible immune-modulation rationale meets a properly sized trial.
How it is thought to work
The mechanistic account, set out in a review by Goldstein and Goldstein (Expert Opinion on Biological Therapy 2009; PMID 19392576), positions thymosin alpha-1 as a biological response modifier acting on:
- Maturation and function of T-cells, reflecting its thymic origin.
- Dendritic cells and other antigen-presenting cells.
- Toll-like receptor signalling in the innate immune system.
That review also lists the investigational territory it has been proposed for — septic shock, ARDS, peritonitis, cytomegalovirus infection, tuberculosis, and chemoprotection during cancer chemotherapy. Breadth of proposed application is a feature of immune modulators generally, and it is not evidence of benefit in any of those settings.
Not the same as thymosin beta-4
The naming causes persistent confusion. Thymosin alpha-1 and thymosin beta-4 (sold as TB-500) are unrelated molecules that share a name only because both were first isolated from thymic tissue extracts. Alpha-1 is an immune signalling peptide with regulatory approvals; beta-4 is an actin-binding peptide studied for cell migration and tissue repair, with no approvals anywhere. They are not interchangeable and their evidence bases have nothing in common.
Evidence and caveats
- Not FDA-approved; approval elsewhere does not transfer.
- The hepatitis literature is heavily concentrated in Chinese trials, and pooled adjunct benefit narrowed to non-significance by one year in the cirrhosis meta-analysis.
- The largest and most rigorous trial in the compound's history was null.
- Benefit demonstrated as an adjunct to antivirals says nothing about standalone use.
- No trial has evaluated it for general immune support in healthy adults — the use most often marketed.