Research in plain language

Thymosin Alpha-1

What it is

Thymosin alpha-1 (thymalfasin, brand name Zadaxin) is a synthetic 28-amino-acid peptide identical to a fragment of the natural thymic hormone prothymosin alpha. It is an immune modulator: it boosts the maturation and activity of T-cells, dendritic cells and antibody responses while damping excessive inflammation. It has been studied as a treatment for chronic hepatitis B and C, as supportive therapy in sepsis, and as an add-on (adjuvant) to vaccines and cancer therapy.

How studies used it

Model: Human, adults with sepsis (Sepsis-3 criteria), 22 centres in China
Studied for: Sepsis (28-day mortality, immune modulation)
Dose: 1.6 mg per dose (absolute). Mean/median body weight was not reported in the trial. At a reference adult weight of about 70 kg this is roughly 0.023 mg/kg per dose; this per-kg figure is an estimate at an assumed weight, not a trial-reported value.
Dosing: Every 12 hours (twice daily)
Route: subcutaneous
Duration: 7 days

Effects measured: Largest and most rigorous trial to date (TESTS, phase 3, double-blind, placebo-controlled, modified intention-to-treat n=1089). 28-day all-cause mortality was 23.4% (127/542) with thymosin alpha-1 versus 24.1% (132/547) with placebo: hazard ratio 0.99 (95% CI 0.77 to 1.27; P=0.93). No clear mortality benefit. No secondary or safety outcome differed significantly between groups. Authors noted possible signals in elderly and diabetic subgroups, but these are exploratory only.

Side effects: No safety outcome differed significantly between thymosin alpha-1 and placebo in this study.

Sources: Wu J, et al. The efficacy and safety of thymosin alpha1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025.

Model: Human, adults with severe sepsis, 6 tertiary hospitals in China
Studied for: Severe sepsis (28-day mortality, immune restoration)
Dose: 1.6 mg per dose (absolute). Body weight was not reported in the trial. At a reference adult weight of about 70 kg this is roughly 0.023 mg/kg per dose; the per-kg figure is an estimate at an assumed weight, not a trial-reported value.
Dosing: Twice daily for 5 days, then once daily for 2 days (7-day course)
Route: subcutaneous
Duration: 7 days

Effects measured: ETASS trial, multicentre single-blind RCT, 361 patients (181 thymosin, 180 control). 28-day all-cause mortality was 26.0% (47/181) with thymosin alpha-1 versus 35.0% (63/180) with control, an absolute reduction of 9.0%. Relative risk 0.74 (95% CI 0.54 to 1.02); the primary nonstratified comparison was not statistically significant (P=0.062), though the log-rank survival comparison reached P=0.049. Note: this earlier positive-leaning trial was later not confirmed by the larger TESTS trial above.

Side effects: No thymosin alpha-1-related serious adverse event was reported and no treatment was discontinued due to intolerance or adverse events.

Sources: Wu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013.

Model: Human, adults with chronic hepatitis C non-responsive to prior interferon/ribavirin (88% genotype 1)
Studied for: Chronic hepatitis C (sustained virological response as add-on to peginterferon/ribavirin)
Dose: 1.6 mg per dose (absolute). Body weight was not reported for the thymosin dose. At a reference adult weight of about 70 kg this is roughly 0.023 mg/kg per dose; the per-kg figure is an estimate at an assumed weight, not a trial-reported value. (Ribavirin in the same regimen was weight-banded at 800-1200 mg/day.)
Dosing: Twice weekly, alongside peginterferon alfa-2a 180 ug/week and ribavirin
Route: subcutaneous
Duration: 48 weeks

Effects measured: Double-blind multicentre RCT, 552 prior non-responders (275 thymosin, 277 placebo). The primary intention-to-treat sustained virological response (SVR) did not differ: 12.7% with thymosin alpha-1 versus 10.5% with placebo (P=0.407). Only in the per-protocol subgroup who completed all 48 weeks was SVR higher (41.0% [34/83] vs 26.3% [26/99]; P=0.048). On-treatment viral response was not increased. Overall the trial was negative for its primary endpoint.

Side effects: No significant difference between groups in the incidence of adverse events.

Sources: Ciancio A, et al. Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role? J Viral Hepat. 2012.

Model: Human, adults with HBeAg-positive, HBV-DNA-positive chronic hepatitis B
Studied for: Chronic hepatitis B (HBV DNA loss / HBeAg seroconversion)
Dose: 1.6 mg per dose (absolute). Body weight was not reported in the trial. At a reference adult weight of about 70 kg this is roughly 0.023 mg/kg per dose; the per-kg figure is an estimate at an assumed weight, not a trial-reported value.
Dosing: Twice weekly
Route: subcutaneous
Duration: 6 months treatment plus 6-month follow-up

Effects measured: Phase III multicentre, randomized, double-blind, placebo-controlled trial, 97 patients (49 thymosin, 48 placebo). Complete response (sustained HBV DNA negativity at month 12) occurred in 14% (7/49) on thymosin versus 4% (2/48) on placebo (P=0.084, not significant). Sustained HBV DNA loss with HBeAg negativity occurred in 25% versus 13% (P about 0.11). The authors stated the results do not confirm the treatment efficacy reported in earlier studies, i.e. this pivotal trial was negative for its primary endpoint.

Side effects: No adverse events were reported in the trial abstract.

Sources: Mutchnick MG, et al. Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. J Viral Hepat. 1999.

Model: Human, elderly men aged 65-99 (mean 77.3 years), n=90 (85 analysed)
Studied for: Influenza vaccine adjuvant (boosting antibody response to trivalent flu vaccine)
Dose: 900 micrograms per square metre of body surface area per dose (published per-BSA dose, not per-kg). The trial dosed by body surface area, not by body weight, and did not report body weight, so a mg/kg value cannot be derived without inventing a weight.
Dosing: Twice weekly for 8 doses, given alongside the 1986 trivalent influenza vaccine
Route: subcutaneous
Duration: About 4 weeks (8 doses over the post-vaccination period)

Effects measured: Double-blind placebo-controlled study. Antibody response was scored as a fourfold or greater rise in titre 3-6 weeks after vaccination, measured by ELISA. The published abstract reports that thymosin alpha-1 augmented the antibody response to influenza vaccine in this elderly male population versus placebo; the abstract text available did not include the full per-strain percentage and p-value breakdown. This is a small, single, decades-old pilot-scale immunogenicity study, not a clinical-endpoint (infection-prevention) trial.

Side effects: No toxicity was observed in either group.

Sources: Gravenstein S, Duthie EH, Miller BA, et al. Augmentation of influenza antibody response in elderly men by thymosin alpha one. A double-blind placebo-controlled clinical study. J Am Geriatr Soc. 1989.

Model: Human, adults with end-stage renal disease on hemodialysis, 5 dialysis centres (Kansas City)
Studied for: COVID-19 prevention / immune support in dialysis patients (pilot)
Dose: 1.6 mg per dose (absolute). Body weight was not reported in the trial. At a reference adult weight of about 70 kg this is roughly 0.023 mg/kg per dose; the per-kg figure is an estimate at an assumed weight, not a trial-reported value.
Dosing: Twice weekly for 8 weeks (then 4 months of follow-up)
Route: subcutaneous
Duration: 8 weeks dosing, 4 months follow-up

Effects measured: Randomized 1:1 pilot trial, preliminary report. Deaths were 3 in the thymalfasin group versus 7 in the control group, and COVID-19-related serious adverse events were 5 versus 7, both numerically lower with thymalfasin but reported descriptively without statistical testing. Planned antibody and lymphocyte-count analyses were still pending at the time of this preliminary report, so no efficacy conclusion can be drawn. Hypothesis-generating only.

Side effects: Serious adverse events occurred in 27 subjects in the thymalfasin group versus 26 in the control group, i.e. comparable between groups; no thymalfasin-specific safety signal was highlighted.

Sources: Tuthill CW, Awad A, Parrigon M, Ershler WB. A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report. Int Immunopharmacol. 2023.

How solid the evidence is

All six entries are real, PubMed-verified human trials (titles, authors and years confirmed on PubMed/PMC). Evidence quality is mixed and, on the strongest endpoints, largely disappointing, so this should not be oversold. Sepsis: The single best-powered study is TESTS (BMJ 2025, n>1000, double-blind, placebo-controlled), and it was clearly NEGATIVE for 28-day mortality (HR 0.99, P=0.93). The earlier ETASS trial (2013, n=361, single-blind) showed a 9% absolute mortality reduction but missed statistical significance on its primary nonstratified analysis (P=0.062) and was only single-blind, a weaker design. So the apparent early benefit did not survive a rigorous larger replication. Meta-analyses that pooled many small, mostly Chinese, single-centre RCTs reported a mortality benefit (e.g. RR around 0.59), but these are dominated by small lower-quality trials and are at odds with TESTS. Hepatitis B: The pivotal phase III placebo-controlled trial (Mutchnick 1999) was NEGATIVE for its primary endpoint (complete response 14% vs 4%, P=0.084) and the authors explicitly said it did not confirm earlier positive reports. This is old (1999) and the modern standard of care for hepatitis B (nucleos(t)ide analogues) is far more effective. Hepatitis C: The Ciancio 2012 RCT (n=552) was NEGATIVE on intention-to-treat SVR (12.7% vs 10.5%, P=0.407). Only a per-protocol subgroup analysis was positive, which is a weaker, post-hoc-type signal. Also, hepatitis C is now cured by direct-acting antivirals, so this indication is largely historical. Vaccine adjuvant: The Gravenstein 1989 elderly-flu study is small (n about 90), single, decades-old, and measures only an immunogenicity surrogate (antibody titre rise), not actual infection prevention. COVID-19/dialysis: Tuthill 2023 is an explicitly preliminary pilot with descriptive numbers only, key analyses pending, and no statistical testing: hypothesis-generating, not evidence of efficacy. Note this study was authored by people affiliated with the drug's developer (Tuthill/SciClone lineage), a potential sponsor-interest consideration. Consistent positive across all studies: SAFETY. Across every trial, thymosin alpha-1 was well tolerated, with adverse events comparable to placebo/control and side effects generally limited to mild injection-site reactions where reported; no serious drug-related toxicity was identified. Doses were given as absolute amounts (1.6 mg) or per body-surface-area (900 ug/m2); none of the abstracts reported mean body weight, so the mg/kg figures shown are reference-weight estimates (about 0.023 mg/kg at 70 kg) and are explicitly flagged as such, not trial-reported per-kg doses.

Sources

Study data, research use only. No established human dosing protocol.