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Thymosin Alpha-1 Seasonal Use Considerations

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At a glance

  • Drug / Thymosin alpha-1 (thymalfasin), a 28-amino-acid peptide [1]
  • US status / Not FDA-approved; no US-approved dose [1]
  • Seasonal evidence / Labelled schedule is vaccination-linked, not seasonal [1]
  • Labelled use / Adjuvant to influenza vaccination in immunocompromised people in Italy [1]
  • Labelled dose / 1.6 mg subcutaneously or intramuscularly twice weekly for 4 weeks per vaccination [1]
  • Safety concern / FDA cites immunogenicity risk for certain routes and inadequate safety information [2]
  • Sport status / Not named on WADA's 2026 or 2027 Prohibited List [3]

What season-related evidence exists for thymosin alpha-1?

What is known is narrower than a seasonal protocol. Thymosin alpha-1 is an immune modulator described as augmenting T-cell function [4]. In healthy volunteers, subcutaneous injection produced peak levels at about 0.7 to 2 hours, a half-life of about 1.8 to 2.6 hours, and no accumulation after daily dosing for five days [1][4].

Season itself affects immune markers. A 2015 study found more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue with seasonal expression profiles, and a pro-inflammatory transcriptomic profile in European winter, including higher soluble IL-6 receptor and C-reactive protein [5]. That work did not test thymosin alpha-1 or any dosing calendar for it.

What is Italy's labelled vaccination schedule?

Zadaxin is the finished injection sold outside the US, 1.6 mg per vial; it is not interchangeable with bulk thymosin alpha-1 powder [1]. Italy authorises Zadaxin as an adjuvant to influenza vaccination in immunocompromised people [1]. The label gives 1.6 mg powder subcutaneously or intramuscularly twice weekly for 4 weeks starting at the first vaccination, repeated from week 8 to week 12 at the second vaccination [1]. The schedule is anchored to vaccination dates.

The label says not for children, is contraindicated in pregnancy and breastfeeding, advises caution in people with allergies or autoimmune disease, and advises caution with other immune-modulating drugs [1].

What do the clinical trials show?

The hepatitis B trials are the main efficacy data, and they are not seasonal. A 2026 Cochrane review pooled 10 randomized trials with 1,349 adults, published from 1991 to 2018 in Bangladesh, China, Italy, Korea, Singapore and Taiwan [6]. It found possible lower all-cause mortality with thymosin alpha-1 (risk ratio 0.53, 95% CI 0.29 to 0.96; 3 trials, 907 people; very low certainty), little to no effect on quality of life or liver histology, and reviewers who said they were not sure it helps [6].

In a double-blind trial of 98 adults with HBeAg-positive hepatitis B, adding thymosin alpha-1 to lymphoblastoid interferon for 24 weeks produced HBeAg loss at 72 weeks in 45.8% versus 28.0% with interferon alone (difference 17.8%, 95% CI -1.2 to 35.3, P=0.067), which was not statistically significant [7]. An earlier randomized trial of 98 patients reported complete virological response at 18 months in 40.6% after 26 weeks of thymosin alpha-1 and 26.5% after 52 weeks, versus 9.4% with no treatment; no significant side effects were observed [8]. A 1991 pilot in 12 people, using thymosin fraction 5 or thymosin alpha-1, found HBV DNA clearance in 6 of 7 treated patients versus 1 of 5 on placebo (P<0.04) [9].

What is the US regulatory status?

Thymosin alpha-1 is not FDA-approved. FDA's Drugs@FDA search found no US application; four US orphan drug designations are a separate process and not an approval [1]. FDA's December 2024 review lists approvals in Italy, India and Hong Kong [1]. Two older reviews with authors tied to the developer say over 35 countries in 2009 or more than 30 countries in 2007 [10][11].

FDA's list for state-licensed pharmacies and physicians places thymosin alpha-1 in none of its three categories [12]. On FDA's list for outsourcing facilities it is category 3, nominated without adequate support [13]. FDA's Pharmacy Compounding Advisory Committee voted 4 yes and 17 no, with no abstentions, on both the free base and acetate forms in December 2024 [14]. It is not one of the six peptides in HHS's October 2026 draft enforcement-discretion policy [15].

FDA still posts safety concerns: significant risk for immunogenicity for certain routes of administration, peptide-impurity and characterization problems, and safety information it calls inadequate to understand the extent of any safety issues [2]. It appears in the nominated-but-withdrawn table after the nominators withdrew, not in the active category 2 table [2]. WADA does not name thymosin alpha-1 on its 2026 or 2027 Prohibited List; WADA does name thymosin-beta-4 and TB-500, which are different peptides [3].

What side effects are known?

FDA's search of its adverse-event database on April 22, 2024 found zero reports for thymosin alpha-1 [1]. Authors tied to the manufacturer report more than 4,400 people enrolled in trials and more than 17 million doses of Zadaxin given after marketing, with adverse experiences described as infrequent and mild; that is company-linked data [1]. In the 2026 Cochrane review, thymosin alpha-1 may have caused fewer serious adverse events than comparison treatments (risk ratio 0.72, 95% CI 0.53 to 0.99; 5 trials, 1,056 people; low-certainty evidence) and fewer non-serious adverse events (risk ratio 0.47, 95% CI 0.27 to 0.83; very low-certainty evidence) [6].

Frequently asked questions

Is there a seasonal dosing schedule for thymosin alpha-1?
The closest labelled schedule is Italy's Zadaxin regimen: 1.6 mg subcutaneously or intramuscularly twice weekly for 4 weeks starting at the first influenza vaccination, repeated from week 8 to week 12 at the second vaccination in immunocompromised people [1]. It is tied to vaccination dates, not to a general season [1].
Is thymosin alpha-1 FDA-approved?
No. FDA's Drugs@FDA search found no US application. Four US orphan drug designations are not an approval [1]. FDA lists approvals in Italy, India and Hong Kong [1].
Is thymosin alpha-1 on WADA's prohibited list?
It is not named on WADA's 2026 or 2027 Prohibited List. WADA does name thymosin-beta-4 and TB-500, which are different peptides [3].
What are the main label cautions?
The Italian label says not for children, contraindicated in pregnancy and breastfeeding, caution in people with allergies or autoimmune disease, and caution with other immune-modulating drugs [1]. FDA separately cites immunogenicity risk for certain routes and inadequate safety information [2].

References

  1. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  2. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks | FDA. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks | FDA
  3. World Anti-Doping Agency. World Anti-Doping Agency
  4. Ancell CD, Phipps J, Young L. Thymosin alpha-1. Am J Health Syst Pharm. 2001;58(10):879-85; quiz 886-8. Thymosin alpha-1
  5. Dopico XC, Evangelou M, Ferreira RC, Guo H, Pekalski ML, Smyth DJ, et al. Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nat Commun. 2015;6:7000. Widespread seasonal gene expression reveals annual differences in human immunity and physiology
  6. Naing C, Ni H, Aung HH, Aye SN, Nikolova D, Poovorawan Y, et al. Thymosin-ɑ1 for people with chronic hepatitis B. Cochrane Database Syst Rev. 2026;9(9):CD014610. Thymosin-ɑ1 for people with chronic hepatitis B
  7. Lim SG, Wai CT, Lee YM, Dan YY, Sutedja DS, Wee A, et al. A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B. Antivir Ther. 2006;11(2):245-53. A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B
  8. Chien RN, Liaw YF, Chen TC, Yeh CT, Sheen IS. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology. 1998;27(5):1383-7. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial
  9. Mutchnick MG, Appelman HD, Chung HT, Aragona E, Gupta TP, Cummings GD, et al. Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial. Hepatology. 1991;14(3):409-15. Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial
  10. Goldstein AL, Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin Biol Ther. 2009;9(5):593-608. From lab to bedside: emerging clinical applications of thymosin alpha 1
  11. Tuthill C. Issues in pharmaceutical development of thymosin alpha1 from preclinical studies through marketing. Ann N Y Acad Sci. 2007;1112:351-6. Issues in pharmaceutical development of thymosin alpha1 from preclinical studies through marketing
  12. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  13. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  14. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  15. Official web page. Official web page
Evidence overview for Thymosin Alpha-1 Seasonal Use Considerations