Thymosin Alpha-1: Approved Abroad, Unapproved in the US

Q: Does thymosin alpha-1 work for sepsis?

The largest trial, TESTS (BMJ, 2025, 1,106 adults in China), found no clear difference in 28-day mortality between thymosin alpha-1 and placebo.

Thymosin alpha-1 is a 28-amino-acid peptide first isolated from the thymus, and its synthetic form, thymalfasin, sold as Zadaxin, is a licensed medicine in dozens of countries but has never been approved by the FDA. Its randomized trials are real and fairly large by the standards of this field, and their results are mixed: a positive signal in some hepatitis trials, a US hepatitis B trial that did not confirm it, and a 2025 sepsis trial of more than 1,000 patients that found no effect on mortality.

That makes it a rare case among peptides discussed online: a compound with a regulatory record abroad and a substantial clinical literature, which still does not add up to a US approval.

What it is

Thymosin alpha-1 was isolated from thymus tissue and characterized by Allan Goldstein in 1977, according to a historical review by Enrico Garaci (Annals of the New York Academy of Sciences, 2007). Reviews describe it as a highly conserved 28-amino-acid peptide (Mao and colleagues, International Immunopharmacology, 2023). Its sequence sits at the start of a larger protein, prothymosin alpha, which Haritos and colleagues (PNAS, 1984) isolated from rat thymus.

It is not related to thymosin beta-4, despite the shared name. Thymosin beta-4 is a 43-amino-acid actin-binding protein studied in tissue repair, covered in our comparison of BPC-157 and TB-500. The two come from different precursors and are studied for different reasons.

The proposed mechanism is immune modulation. Garaci's review describes reports that thymosin alpha-1 increased the expression of MHC class I molecules and toll-like receptors and increased cytokine production, largely from cell and animal work.

Where it is approved

Zadaxin was developed for hepatitis B after Milton Mutchnick, a gastroenterologist at Wayne State University, proposed testing thymosin alpha-1 for the disease in the mid-1980s, according to an account published by AUTM, the technology-transfer association. The same account says the company SciClone received its first approval in China in 1995 and that the drug is approved in 36 countries. In the European Union, the European Medicines Agency lists thymalfasin as authorized in Italy, where it is used to enhance the immune response to influenza vaccine.

The FDA has granted thymalfasin orphan drug designations, for hepatocellular carcinoma according to the EMA's record and for malignant melanoma according to a company announcement. An orphan designation is an incentive for development. It is not an approval.

The US clinical history

Two US trials from the 1990s are the core of the American record.

Hepatitis B. Mutchnick and colleagues (Journal of Viral Hepatitis, 1999) ran a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in 97 patients with chronic hepatitis B, treated for six months and followed for six more. Sustained loss of viral DNA with a negative HBeAg result occurred in 25 percent of the thymosin alpha-1 group and 13 percent of the placebo group, a difference that did not reach statistical significance. The authors wrote that the results did not confirm the efficacy reported in other clinical studies.

Hepatitis C. Sherman and colleagues (Hepatology, 1998) randomized 109 patients with chronic hepatitis C to thymosin alpha-1 plus interferon, interferon plus placebo, or placebo for both. At the end of treatment, a biochemical response (normalized liver enzymes) was seen in 37.1 percent of the combination group, 16.2 percent of the interferon group and 2.7 percent of controls. Sustained biochemical responses were lower, 14.2 percent and 8.1 percent in the combination and interferon groups. The authors described evidence of biological activity and called for further research.

What the wider trial record shows

Hepatitis B, Taiwan. Chien and colleagues (Hepatology, 1998) randomized 98 patients with chronic hepatitis B to a 26-week course, a 52-week course, or no treatment. Eighteen months after entry, the complete virological response rate was 40.6 percent in the 26-week group, higher than in the untreated group, though response rates were similar at the end of therapy. The contrast with the US trial a year later is the reason the hepatitis B evidence is usually described as inconsistent.

Metastatic melanoma. Maio and colleagues (Journal of Clinical Oncology, 2010) randomized 488 patients to combinations of thymosin alpha-1, interferon alfa and the chemotherapy drug dacarbazine. Median overall survival was 9.4 months with thymosin alpha-1 and 6.6 months in the control group, a hazard ratio of 0.80 that did not reach statistical significance (P = .08). The authors concluded the results justified further evaluation.

Sepsis. The TESTS trial (Wu and colleagues, BMJ, 2025) is the largest and most recent. It randomized 1,106 adults with sepsis at 22 centers in China. Twenty-eight-day mortality was 23.4 percent with thymosin alpha-1 and 24.1 percent with placebo, a hazard ratio of 0.99. No secondary or safety outcome differed significantly. The authors reported possible differences by age and diabetes status in prespecified subgroups, and concluded there was no clear evidence that thymosin alpha-1 reduces mortality in sepsis. The paper discloses support from SciClone, among other funders.

COVID-19. Several Chinese studies from 2020, including Liu and colleagues in Clinical Infectious Diseases, reported lower mortality with thymosin alpha-1 in severe COVID-19. They were retrospective cohort studies, which can show an association but cannot establish cause.

Compounding status in the US

Thymosin alpha-1 is not FDA-approved, and its status for US compounding is unsettled. The FDA had placed it in Category 2 of its interim compounding policy, for bulk substances that may present significant safety risks. The FDA's list, last updated in April 2026, now shows it among the substances previously in Category 2 whose nominations were withdrawn. We found nothing placing it in Category 1, the category covered by the FDA's interim enforcement policy.

It was not among the seven peptides reviewed at the July 2026 advisory meeting, and it is not among the five substances the FDA intends to bring to the committee before the end of February 2027, according to a Holland & Knight summary. We found no FDA statement scheduling a review of it. Whether the interim access policy now under White House review covers it is not known, because the policy's text is not public.

Material sold in research channels under the thymosin alpha-1 name is not the licensed product and does not carry its regulatory file. Our explainer on whether peptides are FDA-approved sets out the difference between a licensed medicine abroad and a US approval.

Frequently asked questions

Is thymosin alpha-1 FDA-approved?

No. Its synthetic form, thymalfasin (Zadaxin), is licensed in other countries, 36 according to one published account, but has never been approved by the FDA. It has received US orphan drug designations, which are not approvals.

Why was thymosin alpha-1 not approved in the US?

We found no FDA document explaining a decision. What is on the record is that the US phase 3 hepatitis B trial, published in 1999, did not confirm the efficacy reported in earlier studies.

Does thymosin alpha-1 work for sepsis?

The largest trial, TESTS (BMJ, 2025, 1,106 adults in China), found no clear difference in 28-day mortality between thymosin alpha-1 and placebo.

Is thymosin alpha-1 the same as thymosin beta-4?

No. They are different peptides from different precursor proteins, with different lengths and different research histories.

Sources:

No compound discussed in this review is FDA-approved. Nothing above is dosing guidance or a treatment claim. Research use only.

For research use only · Not for human or veterinary use · No research compound discussed here is FDA-approved for any indication