Thymosin Alpha-1 Side Effects: Incidence Rates Across Clinical Trials
At a glance
- Serious adverse events vs comparator / risk ratio 0.72, 95% CI 0.53 to 0.99, 5 trials, 1,056 people, low certainty [1]
- Non-serious adverse events vs comparator / risk ratio 0.47, 95% CI 0.27 to 0.83, very low certainty [1]
- FDA adverse-event database / zero reports, search dated April 22, 2024 [2]
- US approval status / none; four orphan drug designations are not approvals [2]
What the trial record contains
A small 1991 placebo-controlled pilot trial gave thymosin fraction 5 or thymosin alpha-1 to 7 people with chronic hepatitis B and placebo to 5, twice weekly for six months, and reported no significant side effects [3]. Authors tied to the company that developed Zadaxin report more than 4,400 trial participants and more than 17 million marketed doses, with adverse experiences described as infrequent and mild [2]. That is company-linked data.
The 2026 Cochrane review: the best comparative data
The review pooled 10 randomized trials with 1,349 adults who had chronic hepatitis B, published 1991 to 2018 [1]. Comparators were placebo, no treatment or the same co-treatment. The adverse-event estimates come from a subset of those trials rather than all 10. The risk ratio was 0.72 for serious adverse events (95% CI 0.53 to 0.99; 5 trials, 1,056 people; low certainty) and 0.47 for non-serious events (95% CI 0.27 to 0.83; very low certainty). A ratio below 1 means fewer events with thymosin alpha-1 than with the comparison treatment. The reviewers said they were not sure the drug helps [1].
US adverse-event reports and the Italian label
FDA searched its adverse-event database on April 22, 2024 and found zero reports for thymosin alpha-1 [2].
Italy's Zadaxin label covers 1.6 mg given subcutaneously or intramuscularly twice weekly as an adjuvant to influenza vaccination in immunocompromised people. It says the product is not for children, is contraindicated in pregnancy and breastfeeding, and advises caution with allergies or autoimmune disease and with other immune-modulating drugs [2]. No US label exists [2].
Compounded thymosin alpha-1
FDA's page on bulk substances that may raise significant safety risks when compounded lists thymosin alpha-1 in the nominated-but-withdrawn table. It had been in category 2 and came off because the nominators withdrew. FDA's posted concerns include immunogenicity for certain routes of administration and peptide-impurity problems [4]. In December 2024 the FDA Pharmacy Compounding Advisory Committee voted 4 yes and 17 no on adding thymosin alpha-1 to the pharmacy bulks list [5].
Frequently asked questions
Were side effects less common than with comparison treatments in hepatitis B trials?
Is thymosin alpha-1 FDA approved?
What does the Italian Zadaxin label say?
What is FDA's concern about compounded thymosin alpha-1?
References
- 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. Thymosin-ɑ1 for people with chronic hepatitis B
- U.S. Food and Drug Administration. Thymosin alpha-1 review, December 2024. FDA review of thymosin alpha-1
- 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. Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial
- 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
- U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee, December 4, 2024. FDA advisory committee document