Thymosin Alpha-1
Thymalfasin (Thymosin α1; Tα1)
An endogenous 28-amino acid thymic peptide that modulates innate and adaptive immunity through Toll-like receptor signaling, enhancing dendritic cell maturation, T-cell function, and NK cell activity. Approved in over 35 countries as Zadaxin for hepatitis B/C treatment. Not FDA-approved.
Last updated: 2026-03-12
Safety Summary
Thymosin Alpha-1 has an exceptionally well-documented safety profile across >11,000 patients in 30+ clinical trials. Phase I dose-escalation found no dose-limiting toxicities up to 9.6 mg/m² (highest tested dose; MTD not reached). In the TESTS Phase 3 trial (n=1106), serious adverse events were similar between Tα1 (26%) and placebo (29%). No black box warnings. Long-term use (6--12 months) in hepatitis trials showed consistent safety with no evidence of cancer promotion or organ toxicity. Community users report occasional 'Herxheimer-like' immune flare reactions, particularly in Lyme disease or autoimmune conditions -- recommending starting at lower doses, PMC7747025
Known Side Effects
Common (most frequently reported AE)
Uncommon
Rare (<1%)
Rare (<1%, more common with IFN combination)
Rare
Very rare
Very rare
Who Should NOT Use This
Standard peptide allergy precaution.
Tα1 enhances immune function which could counteract therapeutic immunosuppression and trigger rejection
Immune stimulation could theoretically exacerbate autoimmune conditions. Community reports of immune flares. Use with caution and start at low doses.
Insufficient safety data. Use with caution only if benefit outweighs risk.
Talk to Your Doctor
Before considering Thymosin Alpha-1, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-5]
Evidence Assessment
Approved in >35 countries for hepatitis B/C (Zadaxin). Phase 3 TESTS trial (n=1106, double-blind RCT, BMJ 2024) completed for sepsis but did not meet primary endpoint (28-day mortality HR 0.99, p=0.93), though subgroup interactions were significant. Earlier ETASS trial (n=361) showed borderline benefit (RR 0.74, p=0.062). Meta-analyses of 11--19 smaller sepsis RCTs show pooled mortality benefit (OR 0.73, p=0.003), but driven by small, predominantly Chinese trials with risk of bias. Multiple Phase 2 trials in oncology and infectious diseases. Over 11,000 patients across 30+ clinical trials with consistent safety. Not FDA-approved. Note: Gemini rated Tier 2 based on Phase III existence and international approvals, but the definitive Phase III trial (TESTS) was negative for its primary endpoint. Tier 3 is more conservative and reflects the mixed clinical evidence.
1The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trialPMID 39814420
Wu J, Pei F, Zhou L, et al. - BMJ (2024) - Phase 3 RCT (double-blind, placebo-controlled, multicenter) - 1106 randomized (1089 mITT)
28-day mortality: Tα1 23.4% vs placebo 24.1% (HR 0.99, 95% CI 0.77--1.27, p=0.93). No significant reduction in primary endpoint. Significant subgroup interactions: age <60 HR 1.67 (1.04--2.67) vs -¥60 HR 0.81 (0.61--1.09), Pinteraction=0.01; diabetes HR 0.58 (0.35--0.99), Pinteraction=0.04. Safe: SAEs similar to placebo.
Limitations: Subgroup analyses post-hoc. Predominantly Chinese ICU population. No mortality benefit overall.
2The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial
Gao F, Zhang L, Fan E, et al. - Critical Care (2012) - RCT (single-blind, multicenter) - 361 (181 Tα1, 180 control)
28-day mortality: Tα1 26.0% vs control 35.0% (RR 0.74, 95% CI 0.54--1.02, p=0.062; log-rank p=0.049). Immune markers improved: mHLA-DR day 3 MD 3.9% (p=0.037), day 7 MD 5.8% (p=0.017). No serious drug-related AEs.
Limitations: Single-blind (not double-blind). Borderline statistical significance. Chinese ICU population.
3Systematic review and meta-analysis of thymosin alpha-1 in sepsis
Gu et al. - Various (meta-analysis) (2025) - Systematic review and meta-analysis - 11 RCTs, n=1927
Pooled 28-day mortality OR 0.73 (0.59--0.90, p=0.003). High-quality subgroup OR 0.82 (0.65--1.03, not significant). Significant heterogeneity.
Limitations: Heterogeneity across trials. Many small trials from China. Risk of publication bias. High-quality subgroup did not reach significance.
4Thymalfasin (Thymosin Alpha 1; Ta1) as an Enhancer of Vaccine Response Among Older Adults Receiving Booster Doses of COVID-19 VaccineNCT06821100
The Methodist Hospital Research Institute (sponsor) - ClinicalTrials.gov (2025) - Phase 1 (active, recruiting) - Not specified in registry
Currently recruiting. First US-based clinical trial of Tα1 as vaccine adjuvant in elderly. No results yet.
Limitations: Phase 1 only. Results pending.
5Thymosin Alpha 1 (Tα1) -- A Peptide for Use in the Treatment of Viral Diseases (comprehensive review)
Dominari A, et al. - World Journal of Virology (2020) - Comprehensive literature review - Review of >30 trials, >11,000 patients
Tα1 demonstrates immunomodulatory activity across multiple viral diseases (HBV, HCV, HIV, COVID-19). Safety profile excellent across large patient populations. Enhances vaccine responses in elderly.
Limitations: Review, not primary data. Heterogeneous trial quality.