---
slug: thymosin-alpha-1
title: Thymosin Alpha-1: Approvals, Trial Record, Dosing and What It Does Not Treat
canonical: https://miscsubjects.com/a/thymosin-alpha-1
---

Thymosin alpha-1 is a chain of 28 amino acids that the thymus gland releases into the blood, where it tells immature T cells to finish growing up. The synthetic copy is called thymalfasin, it is sold as Zadaxin, and it is a licensed prescription medicine in roughly 35 countries — which makes it the only compound in this library that a drug regulator anywhere has ever approved.

That single fact reorders everything else, so take the evidence state before anything is argued from it. Most peptides in this library have animal data and a handful of uncontrolled human reports. Thymosin alpha-1 has 63 studies registered on ClinicalTrials.gov, four completed phase 3 programmes, a licensed package insert with a real dosing schedule, and more than 3,000 patients dosed across over 70 studies since 1979. Two of the randomised trials are large and both missed their main endpoint: TESTS, 1,106 adults with sepsis, where 28-day death was 23.4% against 24.1% on placebo; and TRACE, 508 people with severe pancreatitis, where infected dead tissue came out at 15.7% against 18.1%. Two results went the other way: in chronic hepatitis B on its own the odds of clearing the virus and holding it cleared came out 2.87 times placebo, and in a 120-person randomised trial in dialysis patients the drug carried a flu vaccine over the European licensing threshold that the vaccine alone did not reach. One observational study in COVID-19 recorded worse outcomes. The animal record is mice, and its cleanest single result is that the whole effect vanishes in mice bred without the TLR9 receptor. Then the absence that governs this page: across all 63 registered trials there is no tendon, no ligament, no disc, no muscle and no joint. Nothing has been measured in a person for any musculoskeletal problem, and no animal model of one has been run either.

One disclosure, because it should change how you read the rest. The operator of this site has a commercial interest in compounds described here. That is a reason to weigh what is on this page against the sources it cites rather than against its tone, and every claim below carries the source that supports it for exactly that reason.

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## Approved in Beijing, unapproved in Bethesda

Thymalfasin holds marketing approvals for chronic hepatitis B, chronic hepatitis C, use as a vaccine adjuvant in immunocompromised patients, and certain cancers, with the exact indication set varying by country. The United States is not among them. Neither is the European Union.

| Jurisdiction | Status | Indications where approved |
|---|---|---|
| China | Approved; marketed as Zadaxin and by domestic manufacturers | Hepatitis B, immune enhancement, vaccine response, critical-illness adjunct |
| Italy | Approved | Hepatitis B, hepatitis C |
| Roughly 35 countries in total | Approved | Hepatitis B, hepatitis C, vaccine adjuvant, certain cancers, per each national label |
| United States | **Not approved.** No Drugs@FDA entry, no FDA-approved label, no openFDA label record | None |
| European Union | **Not approved** | None |

The manufacturer's own monograph puts the count at "over 30 countries" and states the exclusion in one sentence: "ZADAXIN has not been approved for sale in the United States or Europe." The peer-reviewed literature puts it at "more than 35 countries."

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The US absence is not a rejection on the merits. No sponsor has completed a US registration filing. Thymalfasin has held FDA orphan drug designations — for malignant melanoma, chronic active hepatitis B, DiGeorge anomaly with immune defects, and hepatocellular carcinoma. A designation is a development incentive: fee waivers, tax credits, and seven years of market exclusivity if the drug is later approved. It is not an approval, it permits no marketing, and it carries no finding about whether the drug works. Sources that describe those designations as approvals are wrong, and the distinction is the whole of the US position.

## Withdrawn from the danger list is not the same as cleared for use

The entire United States position turns on one table on one FDA page, and the row is easy to misread.

FDA maintains a page titled *Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks*. It carries two tables. The first is Category 2 proper — substances FDA has flagged as posing significant safety risks, which bars compounding under the interim policies. The second is headed *Bulk drug substances nominated but withdrawn*, described as substances "previously in category 2 of the interim policies" that "were withdrawn by the nominators."

Thymosin-alpha 1 sits in the second table, alongside BPC-157, KPV, TB-500, epitalon, semax, selank and DSIP. FDA's recorded concern reads:

> Compounded drugs containing thymosin-alpha-1 (Ta1) may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. The safety-related information is inadequate for the agency to sufficiently understand the extent of any safety issues raised by the proposed compounded drug.

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Three consequences follow, and they are not the same as each other.

Withdrawal is a procedural act by the party who filed the nomination. It removes the substance from the active Category 2 listing. It is not FDA finding the substance safe, and no agency review concluded in the substance's favour.

Absence from Category 2 creates no permission. To be lawfully compounded from a bulk substance under section 503A, a substance must be the subject of an applicable USP or National Formulary monograph, be a component of an FDA-approved drug, or appear on the 503A bulks list. Thymosin alpha-1 is none of the three in the United States. The 503B outsourcing-facility channel is separate, narrower, and does not list it either.

The practical position in the United States is therefore an unapproved drug obtainable only through the grey market or a compounder operating outside the bulks framework. Any source still describing it as "FDA Category 2" is quoting a status the current page no longer assigns to it. That page was last updated 22 April 2026.

## It gives back a signal the thymus stops sending

The thymus is largest in childhood and shrinks from puberty onward. By the sixth decade most of its functional tissue has been replaced by fat, and the output of new naive T cells falls with it. Thymosin alpha-1 is one of the peptides that tissue secretes; circulating levels in healthy adults run between 0.1 and 1 ng/mL and are lower in disease.

The mechanism reads as a chain. The links are not equally well established, and the difference matters.

**Step one — it binds Toll-like receptors on dendritic cells.** This is the anchoring finding and it is demonstrated directly. In mice, thymosin alpha-1 activated plasmacytoid dendritic cells through TLR9 and MyD88, switching on interferon regulatory factor 7 and driving an interferon-alpha and interferon-gamma effector response. Mice lacking TLR9 lost the protection. That is a knockout-confirmed dependency, not a correlation.

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**Step two — the dendritic cell decides what kind of immunity follows.** Dendritic cells read an infection and instruct the rest of the immune system. Priming them through TLR/MyD88 produced Th1-type antifungal resistance in living animals. The same work found thymosin alpha-1 inducing indoleamine 2,3-dioxygenase in dendritic cells — the enzyme that pushes toward tolerance rather than attack.

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**Step three — T cells mature and differentiate.** The 1972 characterisation was of a thymic fraction that restored immune function to thymectomised mice. The measurable human version is a rise in CD4+ percentage and a normalising CD4+/CD8+ ratio. A meta-analysis of five randomised trials in severe acute pancreatitis quantified it: CD4+ percentage rose by 4.53 points (95% CI 3.02 to 6.04) and the CD4+/CD8+ ratio by 0.42 (95% CI 0.26 to 0.58). CD8+ counts did not fall significantly, which is the point — the ratio normalised by lifting the deficient arm.

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**Step four — natural killer cells and cytotoxic T lymphocytes.** Thymosin alpha-1 modulates NK cell maturation and cytotoxic T lymphocyte responses, and raises MHC class I surface expression on tumour cell lines. The target cell becomes easier to see, not only the effector cell more aggressive.

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**Step five — reversal of T-cell exhaustion.** In severe COVID-19 patients, treatment was associated with reduced PD-1 and Tim-3 expression on CD8+ T cells and a rise in T-cell receptor excision circles, the standard marker of fresh thymic output. This is observational human data from a retrospective cohort of 76 patients, not a controlled experiment, and it belongs in a different evidentiary tier from step one.

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What separates this compound from a stimulant is that the same molecule pushes in opposite directions depending on the state it finds. It induces tolerance-promoting IDO in one context and interferon-driven antiviral attack in another. That bidirectionality is why the literature calls it restoration rather than stimulation. It is also why the dose-response is not a straight line, and why the sepsis subgroups below point in opposite directions in different patients.

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## Sixty-three registered trials, and the two largest disagree

Sixty-three studies are registered on ClinicalTrials.gov with thymosin alpha-1 as an intervention. The named human record is set out below with the result stated as each trial reported it, including the failures.

| Trial | NCT | n | Population | Dose | Duration | Primary endpoint | Result |
|---|---|---|---|---|---|---|---|
| TESTS — phase 3, quadruple-blind, 22 centres | NCT02867267 | 1,106 | Sepsis-3 adults, 18–85 | 1.6 mg SC every 12 h | ≤7 days | 28-day all-cause mortality | **Missed.** 23.4% vs 24.1% placebo; HR 0.99 (0.77–1.27); P=0.93 |
| ETASS — RCT, single-blind, 6 centres | NCT00711620 | 361 analysed | Severe sepsis | 1.6 mg SC twice daily ×5 d, then daily ×2 d | 7 days | 28-day all-cause mortality | Borderline. 26.0% vs 35.0%; RR 0.74 (0.54–1.02); P=0.062 unstratified, 0.049 log-rank |
| TRACE — phase 4, double-blind, 16 centres | NCT02473406 | 508 | Predicted severe acute necrotising pancreatitis | 1.6 mg SC q12h ×7 d, then daily ×7 d | 14 days | Infected pancreatic necrosis | **Missed.** 15.7% vs 18.1%; difference −2.4% (−7.4 to 5.1); P=0.48 |
| TRACE post-hoc, lymphocyte-stratified | NCT02473406 | 290 of 502 | Same trial, baseline ALC ≥0.8×10⁹/L | as above | 14 days | Infected pancreatic necrosis at 90 d | Positive in subgroup. Adjusted risk difference −0.12 (−0.21 to −0.02); P=0.015 |
| Hepatitis C non-responders — phase 3, 52 European sites | NCT01178996 | 552 | Chronic HCV, prior peg-IFN + ribavirin failure | 1.6 mg SC twice weekly + peg-IFN α-2a + ribavirin | 48 weeks | Sustained virological response at week 72 | Completed July 2009. **No results posted or published** |
| Hepatitis C non-responders, non-cirrhotic — phase 3 | NCT00040027 | 500 | Chronic HCV interferon non-responders | 1.6 mg twice weekly + peg-IFN α-2a | — | Virological response | Completed. **No results posted** |
| Metastatic melanoma — phase 2, dose-ranging, 5 arms | NCT00911443 | 488 | Stage IV melanoma | 1.6, 3.2 or 6.4 mg SC on days 8–11 and 15–18 of each 28-day cycle | ≤6 cycles | Overall tumour response | Responders 7/97, 10/97, 6/98, 12/99 in the four Tα1 arms vs 4/97 control. Median OS 8.6–10.3 months vs 6.6 |
| COVID-19 prevention in dialysis — phase 2 | NCT04428008 | 189 | ESRD on haemodialysis | 1.6 mg SC | 6 months | Number infected with COVID-19 | 5/91 treated vs 7/98 control. Deaths 3/91 vs 7/98. Underpowered for both |
| COVID-19 with lymphocytopenia — phase 2 | NCT04487444 | 56 | Hospitalised, lymphocytopenic | 1.6 mg SC daily ×7 d | 1 week | Time to freedom from respiratory failure | **Terminated** February 2023. No results posted |
| H1N1 vaccine adjuvant pilot | NCT01031966 | 120 enrolled, 94 ITT | ESRD on chronic dialysis | 3.2 mg or 6.4 mg on day −7 and day 0 | 2 doses | Antibody response measured by haemagglutination-inhibition | Positive. CHMP licensing criteria fully met in both Tα1 arms, not in vaccine-only |
| Colorectal cancer adjuvant — phase 3 | NCT05086614 | 2,500 planned | Resected high-risk stage II/III colorectal cancer | 1.6 mg SC twice weekly | 6 months | 3-year disease-free survival | **Recruiting.** Primary completion March 2027 |
| Acute aortic dissection, immune dysregulation | NCT05339529 | 330 | Post-operative acute aortic syndrome | Per protocol | — | Organ dysfunction | Recruiting |
| Vaccine response in older adults — phase 1 | NCT06821100 | 75 | Adults over 65 receiving COVID-19 vaccine | Per protocol | — | Immune response | Recruiting |

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## Hepatitis is the indication the licences rest on

The approvals were granted on chronic hepatitis B. An independent meta-analysis of 435 patients across randomised controlled trials of thymalfasin monotherapy found a sustained virological response advantage over placebo with an odds ratio of 2.87 (95% CI 1.58–5.22, P=0.0005), and a non-significant trend favouring it over interferon alpha (OR 2.62, 95% CI 0.80–8.56). Across the individual monotherapy studies, disease remission ran 26% to 41%.

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Two caveats belong in the same breath. The comparator was interferon or placebo, in an era before tenofovir and entecavir; a 2020 review states plainly that hepatitis B and C treatment with thymosin alpha-1 "has been discontinued in favor of direct antiviral agents." And the two large phase 3 hepatitis C programmes in non-responders — 552 and 500 patients, both completed more than fifteen years ago — have never reported. A completed 552-patient phase 3 with no published outcome is not neutral evidence about a drug; it is a hole where the answer should be.

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## Sepsis is where it was tested hardest and came up short

ETASS in 2013 was the encouraging trial. 361 patients, 28-day mortality 26.0% on thymosin alpha-1 against 35.0% on control, plus a measurable rise in monocyte HLA-DR — the clearest available marker of reversed immunoparalysis — at day 3 (mean difference 3.9%, 95% CI 0.2–7.6) and day 7 (5.8%, 95% CI 1.0–10.5). The mortality difference did not clear significance on the primary unstratified analysis at P=0.062.

TESTS was built to settle it. 1,106 patients, 22 centres, quadruple-blinded, placebo-controlled, phase 3. It found nothing: 28-day mortality 23.4% against 24.1%, hazard ratio 0.99, P=0.93. No secondary endpoint separated, and no safety endpoint separated either.

The subgroup analysis is where it stops being simply negative. Patients under 60 did worse on the drug (HR 1.67, 1.04–2.67). Patients 60 and over trended better (HR 0.81, 0.61–1.09). Interaction P=0.01. Diabetic patients did better (HR 0.58, 0.35–0.99), non-diabetic patients did not (HR 1.16, 0.87–1.53), interaction P=0.04. These are prespecified subgroups inside a negative trial. They are hypotheses, and a younger patient doing worse on an immune-restoring drug is a hypothesis worth taking seriously in both directions.

A 2025 meta-analysis pooled 11 randomised trials and 1,927 patients. Overall it found a 28-day mortality benefit (OR 0.73, 95% CI 0.59–0.90, P=0.003). That benefit disappeared when restricted to high-quality trials (OR 0.82, P=0.09) and to multicentre trials (OR 0.86, P=0.20). Trial sequential analysis concluded the accumulated sample is still inadequate to answer the question.

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## Pancreatitis: the trial missed, and one subgroup did not

TRACE randomised 508 patients with predicted severe acute necrotising pancreatitis, 94.3% of whom required intensive care. Infected pancreatic necrosis occurred in 15.7% of treated patients and 18.1% of placebo patients, P=0.48. New-onset organ failure, bleeding and gastrointestinal fistula were all similar between arms.

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The post-hoc analysis found what the whole trial did not. Among the 290 patients whose baseline absolute lymphocyte count was at or above 0.8×10⁹/L, thymosin alpha-1 reduced infected necrosis with an adjusted risk difference of −0.12 (95% CI −0.21 to −0.02, P=0.015). Patients between 0.79 and 2.00×10⁹/L benefited most.

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Read carefully, that is the single most informative result in the file. An immune-restoring drug worked in the patients who still had lymphocytes to restore and did nothing in the patients too depleted to respond. It is post-hoc, it needs prospective confirmation, and it explains why an unselected population produces a null. It also implies that any honest use of this compound starts with a lymphocyte count.

## COVID-19 produced three answers, and one of them was harm

The Wuhan retrospective covered 76 severe cases and reported mortality of 11.11% with treatment against 30.00% without (P=0.044), alongside restored CD8+ and CD4+ counts and reduced exhaustion markers.

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A five-hospital multicentre cohort of 2,282 patients found the reverse. After adjustment for confounders, thymosin alpha-1 use was associated with a *higher* non-recovery rate (OR 1.5, 95% CI 1.1–2.1, P=0.028), with risk concentrated in patients with SOFA scores of 2 or more, ICU admission, and lower PaO₂/FiO₂. Later initiation was worse than earlier.

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A propensity-matched cohort of 1,388 non-severe patients found no difference in progression to severe disease (2.17% vs 2.71%) or in mortality, but shorter viral shedding (13 vs 16 days, P=0.025) and shorter hospital stay (14 vs 18 days, P<0.001).

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All three are observational and all three are subject to confounding by indication — sicker patients get more drugs. The only randomised study that targeted the lymphocytopenic patients the mechanism predicts should respond was terminated at 56 patients and never reported.

## Vaccine response is the cleanest positive signal in the file

Haemodialysis patients mount poor antibody responses to influenza vaccine. In the pilot trial, patients given the adjuvanted H1N1 vaccine alone did not meet the CHMP licensing criteria for seroconversion, seroprotection and geometric mean ratio. Patients given the vaccine plus 3.2 mg or 6.4 mg of thymosin alpha-1 on day −7 and day 0 met all three. No adverse event was attributed to the peptide, and no change appeared in haematology or blood chemistry.

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This is 94 patients in an intention-to-treat analysis, in a population defined by immune failure, in a pilot study. It is also the one result where the drug did the specific thing its mechanism predicts, in humans, judged against a prespecified regulatory standard rather than an author's own endpoint.

## The cancer file is adjuvant work with one real trial still running

The melanoma dose-ranging study is the largest completed oncology dataset: 488 patients across five arms, responses in 6 to 12 patients per thymosin arm against 4 of 97 in the dacarbazine-plus-interferon control, and median overall survival of 8.6 to 10.3 months against 6.6. It was a phase 2 designed to select a dose, not to prove survival, and no phase 3 followed it in the nineteen years since it started.

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The trial that would settle the oncology question is enrolling now: 2,500 patients with resected high-risk stage II and III colorectal cancer, randomised to 1.6 mg twice weekly for six months or to no thymosin, with three-year disease-free survival as the primary endpoint and primary completion in March 2027.

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## Every trial population is an infection, an organ failure or a cancer, and not one of them is a back

Every trial population above is a hepatitis patient, a septic ICU patient, a pancreatitis patient, a cancer patient, or a dialysis patient. Not one is a back-pain patient. There is no musculoskeletal indication, no tendon, ligament, disc or muscle model, and no mechanism connecting T-cell maturation to tissue repair.

| What brings a person to look this up | What the human record actually covers | Strength of the connection |
|---|---|---|
| Recurrent infection, slow recovery from every cold | Vaccine-response pilot in dialysis patients; hepatitis approvals; 3,000-patient safety file | Moderate, and only by extrapolation from immunocompromised populations |
| Documented immunosuppression with a measured low-normal lymphocyte count | TRACE subgroup: the effect appeared where lymphocytes were preserved but suppressed | Moderate. Post-hoc, and it requires the blood test to identify |
| Post-viral fatigue after a confirmed infection | No completed randomised trial. The COVID file is acute hospitalised disease and it contradicts itself | Absent |
| Chronic inflammatory load in a chronic-pain patient | CRP fell 30.12 mg/L in the lower-dose arms of the pancreatitis meta-analysis — in patients with necrotising pancreatitis in intensive care | Absent for this population |
| Immune-related fatigue with no diagnosis and no abnormal labs | No trial, no endpoint, no measurement | Absent |
| Tendinopathy, disc pain, muscle strain, joint repair | No model, no trial, no proposed mechanism | Absent. The extrapolation is unsupported |
| Post-adjustment soreness | Nothing | Absent |
| Hashimoto's, MCAS, ankylosing spondylitis, other autoimmunity | No trial. The mechanism cuts both ways — tolerance in one context, interferon-driven attack in another | Absent, and the self-reports below include people who got measurably worse |

The one row the record can defend is the immune row, in a person with documented immune compromise, and even that defence is an off-label extrapolation from populations that do not look like that person. Selling thymosin alpha-1 for musculoskeletal repair is a claim that nothing in 63 trials supports.

## Dosing, and the arithmetic behind the syringe

The licensed product is a 1.6 mg lyophilised vial supplied with 1.0 mL of Sterile Water for Injection. Reconstituted, that is 1.6 mg/mL, and the whole vial is one dose. The approved hepatitis B regimen is 1.6 mg (900 µg/m²) subcutaneously twice a week for 6 to 12 months. Patients under 40 kg receive 40 µg/kg.

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| Setting | Dose | Frequency | Duration |
|---|---|---|---|
| Hepatitis B — approved label | 1.6 mg SC | Twice weekly | 6–12 months |
| Hepatitis C — phase 3 protocol | 1.6 mg SC | Twice weekly | 48 weeks |
| Sepsis — TESTS | 1.6 mg SC | Every 12 hours | ≤7 days |
| Sepsis — ETASS | 1.6 mg SC | Twice daily ×5 d, then daily ×2 d | 7 days |
| Necrotising pancreatitis — TRACE | 1.6 mg SC | Every 12 h ×7 d, then daily ×7 d | 14 days |
| Colorectal adjuvant — phase 3 | 1.6 mg SC | Twice weekly | 6 months |
| Metastatic melanoma — phase 2 | 1.6, 3.2 or 6.4 mg SC | Days 8–11 and 15–18 of a 28-day cycle | ≤6 cycles |
| Influenza vaccine adjuvant | 3.2 or 6.4 mg SC | Day −7 and day 0 | 2 doses |

The critical-illness regimens run at 3.2 mg per day — twice the hepatitis dose, for one to two weeks. The vaccine regimen runs up to 6.4 mg in a single dose. The cumulative safety record spans 1 mg to 16 mg per dose, and 0.6 to 9.6 mg/m². There is no dose ceiling hiding in that range. There is also nothing showing that a larger dose does more for a stable outpatient.

### Reconstitution, shown as arithmetic

Grey-market vials come as 5 mg or 10 mg of lyophilised powder, not 1.6 mg, so the arithmetic has to be done rather than read off a label.

Concentration in mcg per mL = total micrograms in the vial ÷ millilitres of bacteriostatic water added.
A U-100 insulin syringe holds 1.0 mL across 100 units, so one unit is 0.01 mL, and micrograms per unit = concentration ÷ 100.

Worked: a 10 mg vial holds 10,000 mcg. Add 4.0 mL of bacteriostatic water. 10,000 ÷ 4.0 = 2,500 mcg/mL. 2,500 ÷ 100 = 25 mcg per unit. A 1.6 mg dose is 1,600 ÷ 25 = 64 units on the barrel.

| Vial | Bacteriostatic water added | Concentration | Mcg per unit | Units for 1.6 mg | Full 1.6 mg doses per vial |
|---|---|---|---|---|---|
| 5 mg (5,000 mcg) | 2.0 mL | 2,500 mcg/mL | 25 | 64 | 3, with 200 mcg left over |
| 5 mg (5,000 mcg) | 2.5 mL | 2,000 mcg/mL | 20 | 80 | 3 |
| 5 mg (5,000 mcg) | 5.0 mL | 1,000 mcg/mL | 10 | 160 — two injections | 3 |
| 10 mg (10,000 mcg) | 2.0 mL | 5,000 mcg/mL | 50 | 32 | 6, with 400 mcg left over |
| 10 mg (10,000 mcg) | 4.0 mL | 2,500 mcg/mL | 25 | 64 | 6 |
| 10 mg (10,000 mcg) | 5.0 mL | 2,000 mcg/mL | 20 | 80 | 6 |

At 5,000 mcg/mL — a 10 mg vial in 2.0 mL, the concentration that keeps every trial dose inside one syringe — the conversion is:

| Dose | Micrograms | Units on a U-100 barrel |
|---|---|---|
| 0.25 mg | 250 | 5 |
| 0.5 mg | 500 | 10 |
| 0.8 mg | 800 | 16 |
| 1.0 mg | 1,000 | 20 |
| 1.6 mg | 1,600 | 32 |
| 3.2 mg | 3,200 | 64 |
| 6.4 mg | 6,400 | 128 — two injections |

Below about five units, graduation error on a U-100 barrel starts to dominate the dose, which is the argument for more diluent at the sub-milligram tiers and less at 1.6 mg and above.

Route is subcutaneous in every trial and on every label. Sites are the abdomen at least two inches from the navel, the outer thigh, or the back of the upper arm, rotated between doses. Nothing in the record supports taking this peptide into a muscle, into a vein or by mouth outside a study protocol.

Bring the vial to room temperature before adding water. Run the water down the inside wall rather than jetting it onto the powder. Swirl until dissolved and never shake — shear at the air-liquid interface unfolds peptides and makes them clump, and that clumping is the exact mechanism FDA named when it warned about the immune system reacting to the drug.

### Storage, and the difference the diluent makes

| State | Temperature | Practical shelf life |
|---|---|---|
| Sealed lyophilised vial | 2–8 °C, protected from light | To the manufacturer's date |
| Reconstituted with Sterile Water for Injection — the licensed diluent | — | Use immediately. No preservative present |
| Reconstituted with bacteriostatic water, 0.9% benzyl alcohol | 2–8 °C | About four weeks, set by the preservative rather than by the peptide |
| Reconstituted, held at room temperature | 20–25 °C | Hours to days. Treat as compromised |
| Reconstituted, frozen | −20 °C | Avoid. Freeze-thaw aggregates peptides |

The licensed insert says use immediately because the supplied diluent is preservative-free. A multi-dose vial reconstituted with bacteriostatic water is a different object running a different clock.

### Timelines

Peak serum concentration is reached about 2 hours after a subcutaneous dose, the elimination half-life is about 2 hours, and 31% to 60% of the dose is recovered in urine. The drug leaves the blood the same day. Everything that persists is downstream of what it did to cells, which is why the schedules are twice weekly rather than daily.

| What was measured | When it read out in the trials |
|---|---|
| Monocyte HLA-DR improvement — ETASS | Days 3 and 7 |
| CD4+ percentage and CD4+/CD8+ ratio change | Within the 7–14 day critical-illness courses |
| Vaccine seroconversion — H1N1 pilot | Day 21 after vaccination, dosed day −7 and day 0 |
| Hepatitis B sustained virological response | 6–12 months of dosing, assessed 6 months after treatment |
| Hepatitis C sustained virological response | Week 72, after 48 weeks of dosing |
| Colorectal disease-free survival | 3 years, after 6 months of dosing |

## The safety record is the longest in this library, which is not the same as no risk

Most compounds in this library have no human safety file at all. This one has a specific, quantified record.

Since 1979, thymalfasin has been given to more than 3,000 patients in over 70 clinical studies, at doses from 1 mg to 16 mg, for periods from a single day to 18 months. The monograph's summary sentence is that "no serious adverse experiences have been observed." Patients as old as 101 and children as young as 13 months have been dosed. Patients with decompensated liver disease and patients on haemodialysis tolerated it.

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The label puts drug-related adverse events at under 1% across all indications and describes them as "infrequent and mild, consisting primarily of local discomfort at the injection site, and rare instances of erythema, transient muscle atrophy, polyarthralgia combined with hand edema, and rash." It is contraindicated in hypersensitivity to the drug or its components.

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The controlled trials support that. TESTS randomised 1,106 patients and reported no safety outcome differing significantly between drug and placebo. TRACE randomised 508 and found no difference in bleeding, fistula or new organ failure. The H1N1 pilot attributed no adverse event to the peptide. In the dialysis prevention trial, serious adverse events were 28 of 91 on treatment against 26 of 98 on control, and deaths were 3 of 91 against 7 of 98.

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Preclinical toxicity never reached a maximum tolerated dose. Single subcutaneous doses up to 20 mg/kg in mice, rats and marmosets — more than 800 times the human 1.6 mg dose by weight — produced no drug-related toxicity, as did repeat dosing at 6 mg/kg/day for 13 weeks.

Three qualifications matter more than the reassurance.

**Immune activation can itself be the adverse event.** A 29-year-old man with nasopharyngeal carcinoma received a single 1.6 mg subcutaneous dose eleven days after the checkpoint inhibitor sintilimab. Within 48 hours he had fever of 39–40.5 °C, facial rash and oedema, progressive hypoxaemia with interstitial pulmonary oedema, AST of 742 U/L, and a prothrombin time of 23.2 seconds. He required 160 mg of intravenous methylprednisolone daily and was discharged on day 33. He later tolerated a sintilimab rechallenge without recurrence, which points the causal finger at the peptide rather than the checkpoint inhibitor.

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**The COVID cohort recorded worse outcomes, not merely absent benefit.** An adjusted odds ratio of 1.5 for non-recovery in the sicker patients is a harm signal, and the mechanism is plausible: adding immune activation to a hyperinflammatory state is not obviously safe.

**FDA's stated concern is manufacturing, not what the drug does in the body.** The risk of the immune system reacting to the drug, raised by clumping and by peptide-related impurities, is a supply-chain problem. The 3,000-patient safety record belongs to a pharmaceutical product made to a licensed specification. A grey-market vial carrying a vendor's own certificate of analysis is not that product, and a cloudy reconstitution is a visible sign of the exact aggregation the agency named.

## What people using it outside the trials report

These are self-reports with dates and permalinks, gathered from public discussion. They are not evidence of whether it works, they are not filtered for anything, and they are here because they show what the experience looks like and how often it goes badly.

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[[embed:source:s41]]

The most consistent thread across the positive reports is a flu-like reaction in the first days, which users describe as the immune system waking up.

[[embed:source:s14]]

The negative reports describe the same reaction without the recovery on the other side of it.

[[embed:source:s63]]

[[embed:source:s37]]

[[embed:source:s13]]

Two reports concern measured markers rather than symptoms, in the same condition, and they disagree.

[[embed:source:s38]]

[[embed:source:s59]]

One comment states the risk in exactly the terms the mechanism implies.

[[embed:source:s77]]

And one describes the physical failure mode that FDA's warning is about.

[[embed:source:s84]]

## Proven, unproven, unknown

| Status | Claim |
|---|---|
| Proven | Approved as thymalfasin in roughly 35 countries for hepatitis B, hepatitis C and vaccine adjuvant use |
| Proven | Not approved in the United States or the European Union; no Drugs@FDA entry and no FDA label |
| Proven | Listed in FDA's "nominated but withdrawn" bulk-substances table, not in Category 2, and on neither the 503A nor the 503B bulks list |
| Proven | Acts through TLR9/MyD88/IRF7 on plasmacytoid dendritic cells; the effect is abolished in TLR9-deficient mice |
| Proven | Raises CD4+ percentage by 4.53 points and the CD4+/CD8+ ratio by 0.42 in critically ill humans |
| Proven | Peak serum at about 2 hours, elimination half-life about 2 hours, 31–60% urinary recovery |
| Proven | Sustained virological response advantage in chronic hepatitis B monotherapy, OR 2.87 (1.58–5.22) |
| Proven | Met the European regulator's antibody-response criteria as an influenza vaccine adjuvant in haemodialysis patients where vaccine alone did not |
| Proven | No mortality benefit in sepsis in a 1,106-patient placebo-controlled phase 3 |
| Proven | No reduction in infected pancreatic necrosis in a 508-patient placebo-controlled trial |
| Proven | Drug-related adverse events under 1% across indications in the licensed record, predominantly injection-site discomfort |
| Unproven | Any benefit in post-viral fatigue, chronic fatigue, MCAS, or any autoimmune condition — no completed randomised trial exists |
| Unproven | Benefit in COVID-19. Three observational studies, three different answers, one of them harm |
| Unproven | Whether the pancreatitis lymphocyte-count subgroup effect survives prospective testing |
| Unproven | Whether it improves disease-free survival in colorectal cancer; that trial reads out in 2027 |
| Unknown | The outcome of two completed phase 3 hepatitis C trials totalling 1,052 patients, never reported |
| Unknown | Any effect on tendon, ligament, disc, muscle or joint tissue. No model, no trial, no mechanism |
| Unknown | The correct dose for an outpatient with no diagnosed immune deficiency |
| Unknown | Whether grey-market material matches the pharmaceutical product that generated the safety record |

*Thymosin alpha-1 is not an approved drug in the United States and is not lawfully available there through the bulk-compounding pathways. Nothing here is a dosing or treatment recommendation.*

The sibling objects for this page, each one inspectable on its own terms:

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[[embed:bpc-157]]

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