Thymosin Alpha-1 Research

What thymosin alpha-1 is

Thymosin alpha-1 is a synthetic 28-amino-acid peptide with an acetylated N-terminus. Its sequence matches residues 2 to 29 of prothymosin alpha, and its international nonproprietary name is thymalfasin. PubChem resolves CAS 62304-98-7 and both names to one record, CID 16130571, formula C129H215N33O55, molecular weight 3108.3 ^[28]. FDA's 2024 review prints the same CAS, UNII and molecular weight for the free base ^[23].

Two other CAS numbers circulate for this sequence, and they do not mean the same thing. CAS 69440-99-9 resolves to a different record, CID 16167214, which is a stereochemistry-undefined depiction of the same sequence ^[28]. CAS 69521-94-4 resolves to CID 16130571, the same record as 62304-98-7, so it is an alternate registry form rather than a different molecule ^[28]. The acetate salt has no CAS of its own, and FDA records that it "uses the CAS number of the free base" ^[23]. A certificate quoting 62304-98-7 therefore does not distinguish free base from acetate.

Thymosin alpha-1 and thymosin beta-4 are different molecules

The two share part of a name and little else. Thymosin beta-4 is a 43-amino-acid actin-sequestering peptide, and the parent of the TB-500 fragment ^[28]. Evidence for thymosin beta-4 does not transfer to thymosin alpha-1. Thymopentin, thymulin, and the calf-thymus preparations thymosin fraction 5 and thymostimulin are also distinct substances, and pooled analyses have sometimes combined several of them under one heading ^[15].

Regulatory status is jurisdictional

Thymalfasin holds a national marketing authorization in Italy. The European Medicines Agency states that thymalfasin "is authorised in Italy, where it is used to enhance the immune response stimulated by the influenza virus vaccine" ^[25]. FDA states independently that it "is not approved in the United States, Japan, or Europe (except Italy)" ^[23]. The sponsor's SEC-filed annual report states: "In China, ZADAXIN is approved for the treatment of HBV and for use as an immune system enhancer" ^[26]. The same filing records that the Chinese import drug license has to be renewed every five years ^[26]. China's approval does not cover liver cancer. The filing records only that thymalfasin appears in Chinese Ministry of Health liver-cancer guidelines, and it concedes that off-label use occurs ^[26].

That filing also says the product "is approved in over 30 countries", primarily across the Pacific Rim, Latin America, Eastern Europe and the Middle East ^[26]. FDA reviewed the same claim in an earlier annual report and wrote that it "is unable to independently verify these claims of approval in all the specified countries" ^[23]. The widely repeated figure of 35 countries appears in neither source.

United States status is unambiguous. FDA wrote in December 2024 that "FDA has approved no drug products containing Ta1" ^[23]. The European Union holds only an orphan designation, EU/3/02/110, for hepatocellular carcinoma, designated 30 July 2002 ^[25]. That register states that "An orphan designation is not a marketing authorisation" ^[25]. No EU-wide authorization followed, and none was ever refused or withdrawn.

FDA has granted four orphan designations for thymalfasin, covering chronic active hepatitis B in 1991, DiGeorge anomaly with immune defects in 1998, hepatocellular carcinoma in 2000 and malignant melanoma in 2006 ^[30]. Every one of those records carries an orphan approval status field reading not approved for the orphan indication ^[30]. The sponsor's own annual report lists designations in melanoma, chronic hepatitis B and hepatocellular carcinoma, and speaks of FDA approval only as a future conditional ^[26]. A designation is a development incentive rather than a marketing approval.

On 4 December 2024, FDA's Pharmacy Compounding Advisory Committee considered the free base and the acetate for the 503A bulks list, across twelve proposed uses. FDA's written position was that "a balancing of the four evaluation criteria weighs against" adding either ^[23]. Its stated conclusion across all twelve was a "Lack of evidence to support the effectiveness of SC Ta1 (free base) and Ta1 acetate for the evaluated uses" ^[23]. FDA added that "None of the clinical practice guidelines for U.S. health professionals recommend Ta1 (free base) or Ta1 acetate" ^[23]. A procedural vote returned 20 yes, 1 no and 0 abstentions, and the two substance votes each returned 4 yes and 17 no ^[24].

Mechanism of action

(in vitro, animal) FDA summarizes the mechanism as immunomodulatory, mediated at least in part by interactions with Toll-like receptor 9 on dendritic and lymphoid progenitor cells ^[23]. (animal) Rodent studies report suppressed tumor growth, suppressed viral infection and reduced sepsis ^[23]. (animal) FDA notes that most of those studies used exposures that translate, by body surface area, to human equivalents markedly higher than the exposures used in clinical studies ^[23].

(human) A human pharmacokinetic study covered nine volunteers ^[17]. Time to peak concentration averaged 1 to 2 hours, the elimination half-life was under 3 hours, and exposure did not accumulate across the multiple-dose arm ^[17]. Nothing there supports a prolonged-exposure claim about unmodified thymosin alpha-1.

Sepsis and acute pancreatitis

(human) TESTS randomized 1106 adults with sepsis across 22 centers in China, double-blinded against placebo ^[1]. Mortality at 28 days was 23.4% on drug and 24.1% on placebo ^[1]. A May 2025 BMJ correction restates the 28-day hazard ratio as 0.97 (95% CI 0.76 to 1.24) and the 90-day ratio as 0.95 (0.77 to 1.17) ^[2]. That correction followed pandemic-related data-verification failures, with nine participants wrongly recorded as lost to follow-up ^[2]. Lymphocyte counts were also wrong for 35 of the 1106 participants ^[2]. The authors found "no clear evidence" that the drug reduces 28-day mortality ^[1]. No secondary or safety outcome differed ^[1].

(human) TESTS also carried a harm signal. In the prespecified subgroup of participants under 60 the hazard ratio was 1.67 (1.04 to 2.67), against 0.81 (0.61 to 1.09) at 60 and over, interaction P=0.01 ^[1]. A benefit signal appeared in the prespecified diabetes subgroup, 0.58 (0.35 to 0.99) ^[1]. Subgroup findings inside a null trial are hypothesis-generating.

(human) A second multicenter double-blind trial randomized 508 patients with predicted severe acute necrotizing pancreatitis ^[3]. Infected pancreatic necrosis occurred in 15.7% on drug and 18.1% on placebo, p=0.48 ^[3]. Results were similar across all four predefined subgroups, and organ failure, bleeding and fistula rates did not differ ^[3].

(human) The earlier single-blind sepsis trial that TESTS was built to confirm reported 28-day mortality of 26.0% against 35.0% in 361 patients ^[4]. Its unstratified analysis missed significance at P=0.062, with a relative risk of 0.74 (0.54 to 1.02) ^[4]. Only the log-rank test crossed 0.05, at P=0.049 ^[4]. FDA records no significant difference there in ICU mortality, ICU stay or ventilation duration ^[23].

Human research in hepatitis

(human) A phase 3 double-blind placebo-controlled monotherapy trial in chronic hepatitis B enrolled 97 patients ^[5]. Sustained loss of HBV DNA with negative HBeAg reached 25% on drug and 13% on placebo ^[5]. That difference did not reach significance, at P<0.11 ^[5]. The authors wrote that "These results do not confirm observations of treatment efficacy reported in other clinical studies" ^[5].

(human) The largest hepatitis C trial randomized 552 prior non-responders ^[6]. Sustained virological response in the intention-to-treat population was 12.7% against 10.5%, P=0.407 ^[6]. Among patients completing the full course, rates were 41.0% against 26.3%, P=0.048 ^[6]. That second comparison is post-randomization, covering 83 and 99 patients out of 275 and 277 randomized ^[6]. The authors wrote that thymosin alpha-1 "seems to play no role in the primary therapy of the disease" ^[6].

(human) A 690-patient open-label trial added the peptide to entecavir in HBV-related compensated cirrhosis ^[7]. Cumulative decompensation, hepatocellular carcinoma and death rates were similar between groups, as were virologic, serologic and biochemical responses at week 104 ^[7].

(human) Adding the peptide to peginterferon alfa-2a in 51 HBeAg-positive patients gave a combined response of 15.4% against 12.0% at end of treatment, p=0.725 ^[32]. At end of follow-up the rates were 23.1% and 20.0% ^[32]. The authors wrote that the short-term addition "was not superior to peginterferon alpha-2a alone in HBeAg-positive CHB patients on the basis of antiviral efficacy" ^[32].

(human) A double-blind placebo-controlled trial paired the peptide with lymphoblastoid interferon in 98 HBeAg-positive patients ^[33]. HBeAg loss at 72 weeks was 45.8% against 28.0% ^[33]. That 17.8 percentage-point difference did not reach significance, at P=0.067, and no secondary endpoint reached significance either ^[33]. The authors positioned the finding as needing confirmation in subsequent trials ^[33].

(human) In chronic hepatitis C, a placebo-controlled trial in 109 patients tested the peptide added to interferon ^[34]. End-of-treatment biochemical response was 37.1% for that combination, against 16.2% for interferon and 2.7% for placebo, P=0.04 ^[34]. Cumulative sustained biochemical response was 14.2% against 8.1%, and was not claimed as significant ^[34]. The end-of-treatment difference did not carry through to the sustained endpoint ^[34].

(human) The largest chronic hepatitis B monotherapy dataset randomized 316 Japanese patients between two dose groups, with no placebo arm and no active comparator ^[35]. At week 72 one group recorded 36.4% ALT normalization, 30% HBV DNA clearance by branched-DNA assay and 22.8% HBeAg clearance, and the other group returned similar rates ^[35]. The more sensitive TMA assay put HBV DNA clearance at 15% ^[35]. Without a control arm the trial cannot be read as an efficacy result. It is also the source of the ALT-flare signal FDA cites ^[23].

(human) Two US phase 3 hepatitis C trials, each registered for 500 patients, were announced as negative in December 2005 and June 2006. The comparison in both was against pegylated interferon alpha alone in non-responder patients ^[27]. The sponsor's filing states that they "did not demonstrate that the combination of ZADAXIN and pegylated interferon alpha provides a statistically significant clinical benefit" ^[27]. Both registry records read completed with no results posted, and PubMed returns no publication of either ^[29]. Roughly a thousand enrolled patients are represented only by that filing.

Cancer and COVID-19 evidence

(human) The 488-patient metastatic melanoma trial reported median overall survival of 9.4 against 6.6 months, hazard ratio 0.80, P=0.08, with a progression-free hazard ratio also of 0.80, P=0.06 ^[8]. Neither secondary endpoint reached significance. FDA's read is that the study "Failed to show a significant difference in the ORR with any Ta1 containing regimens compared to the control group" ^[23]. FDA adds that the comparator regimens are "rarely, if ever, used in current clinical practice" ^[23].

(human) A Cochrane review of thymic peptides in cancer covered 26 trials and 2736 patients ^[15]. Only six tested synthetic thymic peptides, and those six pooled thymopentin with thymosin alpha-1 ^[15]. For thymosin alpha-1, pooled overall survival returned a relative risk of 1.21 (0.94 to 1.56, P=0.14) and disease-free survival 3.37 (0.66 to 17.30, P=0.15) ^[15]. Neither reached significance. The review's favorable infection result, 0.54, belongs to the thymus extracts rather than to this molecule ^[15]. Most included trials carried at least a moderate risk of bias ^[15].

(human) Hepatocellular carcinoma carries an open conflict in the literature. An earlier trial of hepatectomy plus chemoembolization, with or without the peptide, reported an overall survival difference ^[23]. The Cochrane group reanalyzed that trial and, on FDA's summary, "did not find a statistically significant difference in either OS or disease-free survival" ^[23].

(human) A US randomized trial in hepatocellular carcinoma added thymalfasin to transarterial chemoembolization in 25 patients ^[36]. Responders were 57.1% against 45.5%, P=1.0, and median overall survival was 110.3 against 57.0 weeks, P=0.45 ^[36]. FDA's read is that the trial showed no significant difference in response rate or in median overall survival ^[23]. FDA also records that the study "was designed primarily as a safety study and therefore was not powered for efficacy outcomes" ^[23].

(human) A COVID-19 meta-analysis of 9 studies and 5352 patients found no significant mortality effect, relative risk 1.03 (0.60 to 1.75), P=0.92, I2 of 90% ^[13]. Its authors concluded that the results "do not support the use of Ta1 in hospitalized adult COVID-19 patients" ^[13]. FDA records that three of four COVID-19 meta-analyses found no mortality reduction ^[23]. (human) A retrospective study of 275 patients found no difference in CD4+ or CD8+ recovery, and longer virus clearance among treated patients in both baseline CD4 strata ^[14].

(human) A widely cited positive COVID-19 trial randomized 105 patients, 40 severe and 65 moderate ^[9]. The figures usually quoted from it, 11.1% against 38.5% mortality, describe the severe stratum rather than the whole cohort ^[9]. The paper reports eight deaths in the entire study, matching 3 of 27 and 5 of 13 severe patients ^[9]. No death occurred in the moderate stratum ^[9]. The same journal issue carried a critical editorial on that trial ^[10]. (human) A US randomized COVID-19 trial of this peptide was terminated early and analyzed 49 patients, with recovery hazard ratios of 1.48 (0.68 to 3.25) and 1.28 (0.35 to 4.63) ^[11]. Its authors state neither difference was significant ^[11].

What FDA found in the other reviewed uses

(human) Italy's approved indication was itself one of the twelve uses FDA reviewed. FDA concluded that "There is lack of sufficient evidence to determine any conclusion on the effectiveness of Ta1 as a vaccine adjuvant" ^[23]. Four of the five studies it reviewed measured ELISA antibody titers rather than clinical effectiveness ^[23]. FDA recorded that control groups were "missing, or inadequate", and that none of the studies used a comparator vaccine recommended in the United States ^[23].

(human) The origin study for that indication was a 1989 double-blind placebo-controlled trial in 90 elderly men, reporting augmented influenza antibody response ^[37]. Its endpoint was a four-fold rise in ELISA antibody titer after trivalent vaccination, not influenza illness ^[37]. Sera from 85 of the 90 men were acceptable for analysis ^[37].

(human) In non-small cell lung cancer, FDA wrote that "There is insufficient evidence to demonstrate the effectiveness of Ta1 as a treatment option for NSCLC" ^[23]. That review covered a set of individual studies going back to 1985, one of them randomized and placebo-controlled, together with two published meta-analyses ^[23].

(human) In chronic obstructive pulmonary disease, FDA reported a "Lack of evidence to support the effectiveness of Ta1 for the treatment of COPD" ^[23]. Of the two studies it reviewed, FDA recorded that "no details of results were provided" ^[23].

(human) In HIV, FDA reviewed four studies and reported that "None of these studies showed increases in CD4+ T cell counts when Ta1 was added" ^[23]. None of them showed an effect on clinical endpoints such as AIDS-defining illness or death, or on viral load ^[23].

(human) After hematopoietic stem cell transplantation, FDA concluded that "These studies do not provide evidence that Ta1 reduces infections and/or infection related mortality after HSCT" ^[23]. One of those studies recorded that the "Infection rate increased in Ta1 treated subjects" ^[23]. FDA also raises a mechanistic concern that the peptide could worsen graft-versus-host disease and lead to engraftment failure ^[23].

In myalgic encephalomyelitis and chronic fatigue syndrome, FDA stated that it "did not identify any clinical studies using Ta1 in subjects with ME/CFS" ^[23]. That is an absence of human evidence rather than weak human evidence, and ME/CFS was still one of the twelve proposed uses FDA evaluated ^[23].

The strongest positive controlled result in this record

(human) In HBV-related acute-on-chronic liver failure, 90-day transplant-free survival was 75.0% (63.2 to 86.8) against 53.4% (39.7 to 67.1), p=0.030 ^[12]. New infection occurred in 32.1% against 58.6%, p=0.005, and hepatic encephalopathy in 8.9% against 24.1%, p=0.029 ^[12]. The trial was open-label with no placebo and enrolled 120 patients ^[12]. Its authors report that "No significant difference was found in the survival using competitive risk analysis" ^[12]. This indication was not among the twelve FDA reviewed ^[23].

A failed replication

(in vitro) A 2017 Nature Medicine paper reported that thymosin alpha-1 corrects the F508del-CFTR defect in cystic fibrosis ^[18]. It drew an author correction and a publisher correction in 2018 ^[18]. Two independent laboratories then reported it "devoid of activity on mutant CFTR" ^[19]. A further group reported that F508del-CFTR "is not corrected by thymosin alpha1" ^[20]. A 2019 study tested the original authors' explanations, rejected them, and recorded that "six independent laboratories failed to demonstrate F508del-CFTR correction" ^[21]. That paper adds that its results do not exclude immunomodulatory effects ^[21].

Trials that were abandoned or never reported

Three phase 2 trials paired the peptide with radiotherapy, in metastatic colorectal cancer, metastatic non-small cell lung cancer and small cell lung cancer ^[31]. All three are recorded as withdrawn with zero enrollment ^[31]. A phase 2 breast cancer trial that included it is recorded as withdrawn, with the reason given as no patients enrolled ^[31]. The 360-patient adjuvant trial in HBV-related hepatocellular carcinoma carries a registry status of unknown, an estimated completion date of October 2018 and no posted results ^[31]. That is a second reporting gap alongside the two unpublished US hepatitis C trials.

Safety signals and conflicts inside the literature

(human) FDA lists local irritation, redness and injection-site discomfort as the most commonly reported adverse events in clinical studies ^[23]. Other reported signals include ALT flares in chronic hepatitis B ^[23][35], TSH abnormalities alongside interferon ^[23], and fatal immune hemolytic anemia and engraftment failure in transplant recipients ^[23]. Foreign product labels for thymalfasin carry warnings or contraindications covering children, pregnancy, lactation, autoimmune disease and immunosuppressed patients ^[23]. FDA names immunogenicity as a specific unresolved risk for an injectable peptide, amplified by aggregation and peptide-related impurities ^[23]. The certificate of analysis submitted for its review carried no results for the control of impurities and aggregates ^[23].

SciClone Pharmaceuticals funded or sponsored the pivotal trials in this record, including the ones that returned null results. TESTS discloses company support for the submitted work, grants to twelve named authors and consultancy fees to three ^[1]. (human) A 2025 sepsis meta-analysis pooled 11 trials and reported a 28-day mortality odds ratio of 0.73 (0.59 to 0.90) ^[16]. Its high-quality subgroup returned 0.82 (0.65 to 1.03) and its multicenter subgroup 0.86 (0.68 to 1.08) ^[16]. Its own trial sequential analysis states the sample size is inadequate ^[16]. Three of its authors were TESTS investigators ^[1][16].

One review often cited in the compound's favor describes itself as a narrative review ^[22]. It concludes that "The FDA's restriction appears unfounded" and recommends that FDA permit compounding pharmacies to compound the peptide ^[22]. That is a position on a regulatory question, not a neutral synthesis.

Conclusion

thymosin alpha-1 holds a national marketing authorization in Italy, covering the immune response to influenza vaccination. China approves it for hepatitis B and as an immune system enhancer. FDA has approved no drug product containing it. Its largest randomized trial, in 1106 adults with sepsis, found no clear evidence of a reduction in 28-day mortality. FDA's December 2024 review reported a lack of evidence of effectiveness across all twelve uses it evaluated. Research-grade material is not a medicine and is not for human consumption.

Frequently Asked Questions

Is thymosin alpha-1 approved anywhere? Yes, in some jurisdictions. Thymalfasin is authorized in Italy for enhancing the immune response to influenza vaccination, and in China for hepatitis B and as an immune system enhancer ^[25][26]. FDA states that it is not approved in the United States, Japan or Europe outside Italy, and that "FDA has approved no drug products containing Ta1" ^[23]. The sponsor claims over 30 countries, and FDA states it cannot independently verify that claim ^[23][26].

Is thymosin alpha-1 the same thing as TB-500? No. TB-500 is a fragment of thymosin beta-4, a 43-amino-acid actin-sequestering peptide ^[28]. Thymosin alpha-1 is a separate 28-amino-acid molecule with its own evidence base ^[28]. The two share part of a name only.

What did the largest randomized trial find? TESTS randomized 1106 adults with sepsis and found 28-day mortality of 23.4% against 24.1% on placebo, with a corrected hazard ratio of 0.97 (95% CI 0.76 to 1.24) ^[1][2]. The authors found "no clear evidence" of a mortality reduction ^[1]. A prespecified subgroup showed a harm signal in participants under 60, at 1.67 (1.04 to 2.67), and another showed a benefit signal in participants with diabetes, at 0.58 (0.35 to 0.99) ^[1]. Subgroup findings inside a null trial are hypothesis-generating.

Has the cystic fibrosis finding been replicated? No. A 2017 Nature Medicine report of F508del-CFTR correction drew two 2018 corrections ^[18]. A 2019 in vitro study recorded that "six independent laboratories failed to demonstrate F508del-CFTR correction" ^[21]. That paper adds that its results do not exclude immunomodulatory effects ^[21].

References

1. 1

   Wu J, et al. BMJ, 2025;388:e082583. PMID 39814420.; DOI: 10.1136/bmj-2024-082583.
2. 2

   Correction. BMJ, 2025;389:r1098. PMID 40447307.; DOI: 10.1136/bmj.r1098. Full text read at PMC12123687.
3. 3

   Ke L, et al. Intensive Care Medicine, 2022;48(7):899-909. PMID 35713670.; DOI: 10.1007/s00134-022-06745-7.
4. 4

   Wu J, et al. Critical Care, 2013;17(1):R8. PMID 23327199.; DOI: 10.1186/cc11932.
5. 5

   Mutchnick MG, et al. Journal of Viral Hepatitis, 1999;6(5):397-403. PMID 10607256.; DOI: 10.1046/j.1365-2893.1999.00181.x.
6. 6

   Ciancio A, et al. Journal of Viral Hepatitis, 2012;19 Suppl 1:52-59. PMID 22233415.; DOI: 10.1111/j.1365-2893.2011.01524.x.
7. 7

   Wu X, et al. Expert Opinion on Biological Therapy, 2018;18(sup1):61-69. PMID 30063860.; DOI: 10.1080/14712598.2018.1451511.
8. 8

   Maio M, et al. Journal of Clinical Oncology, 2010;28(10):1780-1787. PMID 20194853.; DOI: 10.1200/JCO.2009.25.5208.
9. 9

   Shetty A, et al. Indian Journal of Critical Care Medicine, 2022;26(8):913-919. PMID 36042753.; DOI: 10.5005/jp-journals-10071-24298.
10. 10

    Divatia JV. Indian Journal of Critical Care Medicine, 2022;26(8):892-893. PMID 36042755.
11. 11

    Shehadeh F, et al. Journal of Infectious Diseases, 2023;227(2):226-235. PMID 36056913.; DOI: 10.1093/infdis/jiac362.
12. 12

    Chen JF, et al. Hepatology International, 2022;16(4):775-788. PMID 35616850.; DOI: 10.1007/s12072-022-10335-6.
13. 13

    Shang W, et al. International Immunopharmacology, 2023;114:109584. PMID 36527881.; DOI: 10.1016/j.intimp.2022.109584.
14. 14

    Wang Z, et al. Frontiers in Immunology, 2021;12:568789. PMID 34149679.; DOI: 10.3389/fimmu.2021.568789.
15. 15

    Wolf E, et al. Cochrane Database of Systematic Reviews, 2011;2011(2):CD003993. PMID 21328265.; DOI: 10.1002/14651858.CD003993.pub3.
16. 16

    Gu B, et al. Frontiers in Cellular and Infection Microbiology, 2025;15:1673959. PMID 40969554.; DOI: 10.3389/fcimb.2025.1673959.
17. 17

    Rost KL, et al. International Journal of Clinical Pharmacology and Therapeutics, 1999;37(1):51-57. PMID 10027483.
18. 18

    Romani L, et al. Nature Medicine, 2017;23(5):590-600. PMID 28394330. Author Correction PMID 29934534.; Publisher Correction PMID 29934535.
19. 19

    Tomati V, et al. JCI Insight, 2018;3(3):e98699. PMID 29415893.; DOI: 10.1172/jci.insight.98699. Published correction PMID 30944255.
20. 20

    Matthes E, Hanrahan JW, Cantin AM. Nature Medicine, 2018;24(7):890-891. PMID 29942095.
21. 21

    Armirotti A, et al. Scientific Reports, 2019;9(1):10310. PMID 31311979.; DOI: 10.1038/s41598-019-46639-1.
22. 22

    Dinetz E, Lee E. Alternative Therapies in Health and Medicine, 2024;30(1):6-12. PMID 38308608.
23. 23

    US Food and Drug Administration, CDER. Pharmacy Compounding Advisory Committee briefing presentation, thymosin alpha-1 (free base) and thymosin alpha-1 acetate, 4 December 2024. fda.gov/media/183892/download. Retrieved and read in full 28 August 2026.
24. 24

    US Food and Drug Administration. Pharmacy Compounding Advisory Committee meeting transcript, Topic 3, 4 December 2024. fda.gov/media/185640/download. Vote tallies read directly 28 August 2026.
25. 25

    European Medicines Agency. Orphan designation EU/3/02/110, thymalfasin, treatment of hepatocellular carcinoma; designated 30 July 2002. Public register entry retrieved 28 August 2026.
26. 26

    SciClone Pharmaceuticals, Inc. Form 10-K for fiscal year 2016, SEC EDGAR CIK 0000880771, accession 0000880771-17-000035. Retrieved and quoted directly 28 August 2026.
27. 27

    SciClone Pharmaceuticals, Inc. Form 10-K for fiscal year 2008, SEC EDGAR CIK 0000880771, accession 0001193125-09-053980. Retrieved and quoted directly 28 August 2026.
28. 28

    NCBI PubChem. CID 16130571 (CAS 62304-98-7 and CAS 69521-94-4, UNII W0B22ISQ1C, C129H215N33O55, MW 3108.3); CID 16167214 (CAS 69440-99-9); CID 45382195 (thymosin beta-4). Round-tripped via PUG-REST 28 August 2026.
29. 29

    ClinicalTrials.gov registry records NCT00040027 and NCT00039962. Both completed, enrollment 500 each, hasResults false. Retrieved via API v2 on 28 August 2026, with a PubMed search for either identifier returning zero records.
30. 30

    US Food and Drug Administration, Office of Orphan Products Development. Orphan drug designation database, four thymalfasin designations, sponsor SciClone Pharmaceuticals: chronic active hepatitis B designated 05/03/1991; DiGeorge anomaly with immune defects 01/08/1998; hepatocellular carcinoma 03/06/2000; stage IIb through stage IV malignant melanoma 03/13/2006. Each record's FDA Orphan Approval Status field reads "Not FDA Approved for Orphan Indication". Not re-retrieved in this pass: the OOPD listing did not respond to direct queries from this environment on 28 August 2026, so these four rows are reported as previously recorded rather than read live. Three of the four designations are independently corroborated by reference 26.
31. 31

    ClinicalTrials.gov registry records NCT02535988 (colorectal), NCT02542930 (non-small cell lung), NCT02542137 (small cell lung), all withdrawn with actual enrollment 0 and the reason "No recruitment."; NCT00935558, withdrawn, reason "no patients enrolled"; NCT02281266, status UNKNOWN, estimated enrollment 360, completion date 2018-10, hasResults false. Retrieved via API v2 on 28 August 2026.
32. 32

    Kim BH, et al. Scandinavian Journal of Gastroenterology, 2012;47(8-9):1048-1055. PMID 22726105.
33. 33

    Lim SG, et al. Antiviral Therapy, 2006;11(2):245-253. PMID 16640105.
34. 34

    Sherman KE, et al. Hepatology, 1998;27(4):1128-1135. PMID 9537454.
35. 35

    Iino S, et al. Journal of Viral Hepatitis, 2005;12(3):300-306. PMID 15850471.
36. 36

    Gish RG, et al. Hepatology International, 2009;3(3):480-489. PMID 19669251.
37. 37

    Gravenstein S, et al. Journal of the American Geriatrics Society, 1989;37(1):1-8. PMID 2642497.