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Thymosin alpha-1 after TESTS: two large negative trials

It is sold as an "immune optimizer". It is approved in more than 35 countries for hepatitis B and C. But two large double-blind trials, in sepsis and in pancreatitis, showed no benefit. And in patients under 60 a signal pointed the other way.

Published October 9, 2026 · 3 min read · 15 sources

Why thymosin alpha-1 is different

Unlike most trendy peptides, thymosin alpha-1 has a pharmaceutical history: it was isolated from calf thymus in 1977 as a 28-amino-acid peptide8, it has been studied for decades in hepatitis B411 and is approved in more than 35 countries for hepatitis B and C, according to a 2009 review7. That history gives it credibility. That is why the large trials of recent years carry so much weight.

TESTS: the sepsis trial

TESTS was a phase 3, double-blind, placebo-controlled trial at 22 centers in China, with 1,106 patients with sepsis (1,089 in the modified intention-to-treat analysis)14. 28-day mortality was 23.4% with thymosin alpha-1 vs 24.1% with placebo (HR 0.99; 95% CI 0.77–1.27; P = 0.93)1. Earlier, a smaller, single-blind trial (ETASS, 361 patients with severe sepsis) had suggested a benefit: 28-day mortality had been 26.0% vs 35.0%, with an RR of 0.74 (0.54–1.02) and a marginal P value9.

The subgroups showed something uncomfortable: in patients under 60, HR 1.67 (1.04–2.67), a possible harm signal; in patients with diabetes, HR 0.58 (0.35–0.99)1. Subgroups generate hypotheses, not conclusions. The trial was partly funded by SciClone Pharmaceuticals1, the company that also supplied the thymosin alpha-1 in TRACE2. A 2025 meta-analysis of 11 trials found lower mortality overall (OR 0.73), but not in the high-quality (OR 0.82; 0.65–1.03) or multicenter (OR 0.86; 0.68–1.08) subgroups, and concluded that the cumulative sample size is still inadequate10.

HR 0.9928-day mortality in sepsis (TESTS, 1,106 patients)1
HR 1.67under-60 subgroup1
15.7 vs 18.1%infected necrosis in pancreatitis (TRACE)2

TRACE: pancreatitis

In TRACE, 508 patients with predicted severe necrotizing pancreatitis received thymosin alpha-1 or placebo15. Infected pancreatic necrosis was 15.7% vs 18.1% (P = 0.48): negative2. A later analysis by lymphocyte count suggested possible benefit in the subgroup with lymphocytes ≥0.8 × 10⁹/L, but its authors note the subgroup was not prespecified and must be confirmed in a prospective trial3.

Hepatitis B and COVID-19

The 2026 Cochrane review pooled 10 trials with 1,349 patients with chronic hepatitis B (1991–2018). Mortality (3 trials, 907 patients) showed an RR of 0.53 (0.29–0.96), but with very low certainty: "we are not sure whether thymosin-α1 ... reduces all-cause mortality"4. In COVID-19, a meta-analysis of 8 studies gave RR 0.59 with very high heterogeneity (I² = 84%); the authors call for randomized trials5. Observational studies contradict each other: in 76 severe cases in Wuhan, mortality was 11.1% with thymosin alpha-1 vs 30.0% without it12, while in a multicenter cohort of 2,282 patients its use was associated with a higher non-recovery rate (adjusted OR 1.5)13.

Sources

  1. Wu J, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025;388:e082583. PubMed 39814420 ↗
  2. Ke L, et al. Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial. Intensive Care Med. 2022;48(7):899-909. PubMed 35713670 ↗
  3. Ke L, et al. Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial. EClinicalMedicine. 2023;58:101915. PubMed 37007743 ↗
  4. Naing C, et al. Thymosin-α1 for people with chronic hepatitis B. Cochrane Database Syst Rev. 2026;9(9):CD014610. PubMed 42713852 ↗
  5. Soeroto AY, et al. The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression. Inflammopharmacology. 2023;31(6):3317-3325. PubMed 37845598 ↗
  6. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. fda.gov ↗
  7. Goldstein AL, Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin Biol Ther. 2009;9(5):593-608. PubMed 19392576 ↗
  8. Goldstein AL, Low TL, McAdoo M, McClure J, et al. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977;74(2):725-9. PubMed 265536 ↗
  9. Wu J, Zhou L, Liu J, Ma G, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. PubMed 23327199 ↗
  10. Gu B, Zhou Y, Nie Y, Wang L, et al. Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol. 2025;15:1673959. PubMed 40969554 ↗
  11. Chien RN, Liaw YF, Chen TC, Yeh CT, et al. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology. 1998;27(5):1383-7. PubMed 9581695 ↗
  12. Liu Y, Pan Y, Hu Z, Wu M, et al. Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells. Clin Infect Dis. 2020;71(16):2150-2157. PubMed 32442287 ↗
  13. Liu J, Shen Y, Wen Z, Xu Q, et al. Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study. Front Immunol. 2021;12:673693. PubMed 34408744 ↗
  14. ClinicalTrials.gov. NCT02867267: The Efficacy and Safety of Ta1 for Sepsis (TESTS). Completed; actual enrollment 1,106. clinicaltrials.gov ↗
  15. ClinicalTrials.gov. NCT02473406: Thymosin Alpha 1 in the Prevention of Pancreatic Infection Following Acute Necrotizing Pancreatitis (TRACE). Completed; actual enrollment 508. clinicaltrials.gov ↗

Informational article. It summarizes news, official statements and published studies; it is not medical or legal advice. Sources were checked on the publication date.

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