Thymalin
Thymalin is a heterogeneous calf-thymus peptide extract, not the defined nonapeptide thymulin. A developer-run program reported lower mortality in randomized arms of 24 and 22 people within a 266-person observed cohort. The overlapping Russian and English reports have not been independently replicated.
calf-thymus peptide extract
- Calf-thymus peptide mixture
- Different from thymulin
- Developers’ patent specifies a 600 to 6,000 Da band
- Public trial registries list no exact-name Thymalin intervention study.
What exactly is Thymalin?
Thymalin is an acid-extracted calf-thymus peptide mixture spanning a molecular-weight range in the developers’ patent. It has no single sequence or mass and is not thymulin, thymalfasin, thymopentin, or the defined Glu-Trp fraction.
US5070076A · mixture specification
Developer patent
Morozov VG, Khavinson VK. US Patent 5,070,076, granted 1991.
The patent describes a calf-thymus preparation as peptide fractions across roughly 600 to 6,000 Da with process and physicochemical characteristics. It provides no clinical efficacy data or independent batch verification.
- Study design
- Granted composition and process patent
A patent is not a clinical trial, regulator assay, or proof that a current vial matches the claimed process.
Read the original sourceCell study · extract diverged from peptides
In vitro comparative study
Avolio F et al. International Journal of Molecular Sciences, 2022.
Four defined peptides reduced monocyte adhesion in the assay, while the heterogeneous thymalin extract increased it and differed on other cellular outputs. The result demonstrates that named fractions cannot stand in for the parent extract.
- Treatment
- Thymalin extract and four defined peptides in THP-1 cells
- Study design
- Replicated in vitro comparative experiment
Does Thymalin extend human life?
One developer-run program reports lower mortality, but the key randomized comparison was 24 thymalin recipients against 22 placebo recipients inside a 266-person overall dataset. The Russian 2002 and English 2003 publications overlap and do not count as independent replications.
2003 report · small mortality arms inside n=266
Developer-run controlled follow-up report
Khavinson VKh, Morozov VG. Neuro Endocrinology Letters, 2003.
The paper describes 266 older people overall, but the St Petersburg randomized mortality comparison used 24 thymalin recipients and 22 placebo recipients. Over six years, 10 of 24 in the thymalin arm and 18 of 22 in placebo died. The paper reports no confidence intervals, survival model, allocation-concealment detail, or dropout accounting, and the developers authored the work.
- Participants / model
- 266 older adults across St Petersburg and Kyiv cohorts; randomized mortality arms of 24 thymalin and 22 placebo in St Petersburg
- Treatment
- Thymalin, epithalamin, their combination, or placebo in course-based regimens
- Follow-up
- 6 to 8 years of follow-up depending on cohort
- Study design
- Developer-run stratified controlled follow-up, described as double-blind for the St Petersburg arm
The overall 266 is not the denominator for the key thymalin-versus-placebo mortality comparison.
Read the original sourceRussian 2002 paper · duplicate dataset
Russian-language clinical report
Хавинсон ВХ, Морозов ВГ. Успехи геронтологии, 2002.
The Russian-language publication reports the same geroprotective program later published in English in 2003. It is evidence that a Russian human report exists, but it should not be counted as an independent replication.
- Participants / model
- Older adults in the same St Petersburg and Kyiv research program
- Treatment
- Thymalin and epithalamin course-based interventions
- Study design
- Russian-language report of the developer-run controlled cohorts
The 2002 and 2003 reports describe overlapping cohorts and are not independent replications.
Read the original sourceDoes it improve immune outcomes?
The modern 92-person COVID-19 study reported favorable within-group biomarker changes, but no deaths in either arm and no prespecified between-group clinical effect estimate. A separate Russian retrospective report lacks group denominators in its abstract.
Open-label trial · 42 versus 50
Open-label randomized clinical study
Khavinson V et al. Stem Cell Reviews and Reports, 2021.
Forty-two patients received thymalin plus standard care and 50 received standard care. Both arms had no deaths. The paper emphasizes within-group immune and inflammatory marker changes and provides no prespecified between-group clinical effect estimate with confidence interval.
- Participants / model
- 92 hospitalized adults with moderate to severe COVID-19, lymphopenia, and bilateral pneumonia
- Treatment
- Thymalin plus standard care versus standard care
- Follow-up
- Five-day treatment with in-hospital follow-up
- Study design
- Single-center open-label randomized study
Within-group fold changes do not substitute for a direct randomized between-group effect.
Read the original sourceRussian 2022 report · abstract lacks group denominators
Russian-language retrospective study
Кузник БИ et al. Успехи геронтологии, 2022.
The Russian abstract reports mortality percentages for standard therapy, tocilizumab, and thymalin groups but does not state group sizes, so deaths cannot be reconstructed or compared reliably from the abstract alone.
- Participants / model
- Hospitalized people with severe COVID-19; group sizes not reported in the abstract
- Treatment
- Standard therapy, tocilizumab, or thymalin
- Study design
- Retrospective Russian-language comparison
The abstract does not report group sizes, so deaths and treatment effects cannot be reconstructed.
Read the original sourceCan the named short peptides explain the extract?
No. Human-cell experiments show nonspecific immune effects and, in one direct comparison, the extract moved adhesion in the opposite direction from four defined peptides. A mixture cannot inherit a single fraction’s target or clinical result.
Four-donor cell study · in vitro cytokines
Human-cell laboratory study
Linkova N et al. International Journal of Molecular Sciences, 2023.
Peripheral blood mononuclear cells from four donors were exposed to thymalin and two named dipeptides. Several inflammatory outputs changed in vitro. No donor received thymalin and the experiment cannot establish a clinical immune effect.
- Participants / model
- Cultured blood cells from 4 human donors
- Treatment
- Laboratory thymalin, Lys-Glu, and Glu-Trp exposure
- Study design
- In vitro human-cell experiment
Cell study · extract diverged from peptides
In vitro comparative study
Avolio F et al. International Journal of Molecular Sciences, 2022.
Four defined peptides reduced monocyte adhesion in the assay, while the heterogeneous thymalin extract increased it and differed on other cellular outputs. The result demonstrates that named fractions cannot stand in for the parent extract.
- Treatment
- Thymalin extract and four defined peptides in THP-1 cells
- Study design
- Replicated in vitro comparative experiment
Does IM862 prove Thymalin works?
No. IM862 is defined Glu-Trp, one proposed fraction in the broader lineage. Its 202-person phase 3 trial did not improve response over placebo and therefore cannot serve as positive evidence for the heterogeneous parent extract.
Defined Glu-Trp fraction · phase 3 negative
Randomized double-blind placebo-controlled trial of a related fraction
Noy A et al. Journal of Clinical Oncology, 2005.
In 202 participants, response was 23% with IM862 and 21% with placebo (P=.46). Median time to progression was 16 versus 35 weeks (P=.012), although the active arm had less concurrent antiretroviral therapy. This tested defined Glu-Trp, not the parent thymalin extract.
- Participants / model
- 202 people with AIDS-related Kaposi sarcoma
- Treatment
- Intranasal IM862 or placebo
- Follow-up
- 24 weeks
- Study design
- Randomized double-blind phase 3 trial
The negative Glu-Trp trial does not establish the parent extract's efficacy or inefficacy; earlier uncontrolled fraction signals do not establish a Thymalin effect.
Read the original sourceWhat is known about safety?
No adequate human pharmacovigilance table or pharmacokinetic study was identified. The extract adds batch-composition, animal-tissue, immune-reaction, contamination, interaction, pregnancy, and repeated-injection uncertainty; a Russian guinea-pig study supplies an animal sensitization signal only.
Russian animal study · sensitization signal
Russian-language animal study
Суходоева ГС et al. Журнал микробиологии, эпидемиологии и иммунобиологии, 1993.
The Russian-language animal report describes increased sensitization to a microbial antigen after thymalin, with repeated injections producing a stronger effect than a single exposure. It is a heterologous animal-protein extract signal in guinea pigs, not a measured human adverse-event rate.
- Participants / model
- Guinea pigs
- Treatment
- Single or repeated thymalin exposure with microbial antigen challenge
- Study design
- Animal immunogenicity experiment
US5070076A · mixture specification
Developer patent
Morozov VG, Khavinson VK. US Patent 5,070,076, granted 1991.
The patent describes a calf-thymus preparation as peptide fractions across roughly 600 to 6,000 Da with process and physicochemical characteristics. It provides no clinical efficacy data or independent batch verification.
- Study design
- Granted composition and process patent
A patent is not a clinical trial, regulator assay, or proof that a current vial matches the claimed process.
Read the original sourceClinicalTrials.gov/WHO aliases · zero exact records
Trial registrations
ClinicalTrials.gov.
ClinicalTrials.gov lists no exact-name Thymalin intervention study. Older Russian-language clinical reports without matching registrations remain separate evidence.
Read the original sourceIs Thymalin an approved or registered drug?
The cited US and EU records contain no Thymalin approval, and public trial registries contain no exact-name intervention study. A developer-authored account reports a 1982 Soviet registration; that secondary account does not imply US or EU approval. Older unregistered human reports remain separate evidence.
US, EU, and historical Soviet status
Regulatory status
FDA, EMA, and a developer-authored history of Thymalin.
The cited US and EU records contain no Thymalin approval. A developer-authored account reports USSR registration certificate 82/1108/8 under Ministry of Health Order 1108 dated November 10, 1982.
The 1982 registration is supported by a developer-authored account rather than the original certificate and does not imply US or EU approval.
Read the original sourceClinicalTrials.gov/WHO aliases · zero exact records
Trial registrations
ClinicalTrials.gov.
ClinicalTrials.gov lists no exact-name Thymalin intervention study. Older Russian-language clinical reports without matching registrations remain separate evidence.
Read the original sourceStudies and sources
2003 report · small mortality arms inside n=266
Developer-run controlled follow-up report
Khavinson VKh, Morozov VG. Neuro Endocrinology Letters, 2003.
The paper describes 266 older people overall, but the St Petersburg randomized mortality comparison used 24 thymalin recipients and 22 placebo recipients. Over six years, 10 of 24 in the thymalin arm and 18 of 22 in placebo died. The paper reports no confidence intervals, survival model, allocation-concealment detail, or dropout accounting, and the developers authored the work.
- Participants / model
- 266 older adults across St Petersburg and Kyiv cohorts; randomized mortality arms of 24 thymalin and 22 placebo in St Petersburg
- Treatment
- Thymalin, epithalamin, their combination, or placebo in course-based regimens
- Follow-up
- 6 to 8 years of follow-up depending on cohort
- Study design
- Developer-run stratified controlled follow-up, described as double-blind for the St Petersburg arm
The overall 266 is not the denominator for the key thymalin-versus-placebo mortality comparison.
Read the original sourceRussian 2002 paper · duplicate dataset
Russian-language clinical report
Хавинсон ВХ, Морозов ВГ. Успехи геронтологии, 2002.
The Russian-language publication reports the same geroprotective program later published in English in 2003. It is evidence that a Russian human report exists, but it should not be counted as an independent replication.
- Participants / model
- Older adults in the same St Petersburg and Kyiv research program
- Treatment
- Thymalin and epithalamin course-based interventions
- Study design
- Russian-language report of the developer-run controlled cohorts
The 2002 and 2003 reports describe overlapping cohorts and are not independent replications.
Read the original sourceOpen-label trial · 42 versus 50
Open-label randomized clinical study
Khavinson V et al. Stem Cell Reviews and Reports, 2021.
Forty-two patients received thymalin plus standard care and 50 received standard care. Both arms had no deaths. The paper emphasizes within-group immune and inflammatory marker changes and provides no prespecified between-group clinical effect estimate with confidence interval.
- Participants / model
- 92 hospitalized adults with moderate to severe COVID-19, lymphopenia, and bilateral pneumonia
- Treatment
- Thymalin plus standard care versus standard care
- Follow-up
- Five-day treatment with in-hospital follow-up
- Study design
- Single-center open-label randomized study
Within-group fold changes do not substitute for a direct randomized between-group effect.
Read the original sourceRussian 2022 report · abstract lacks group denominators
Russian-language retrospective study
Кузник БИ et al. Успехи геронтологии, 2022.
The Russian abstract reports mortality percentages for standard therapy, tocilizumab, and thymalin groups but does not state group sizes, so deaths cannot be reconstructed or compared reliably from the abstract alone.
- Participants / model
- Hospitalized people with severe COVID-19; group sizes not reported in the abstract
- Treatment
- Standard therapy, tocilizumab, or thymalin
- Study design
- Retrospective Russian-language comparison
The abstract does not report group sizes, so deaths and treatment effects cannot be reconstructed.
Read the original sourceUS5070076A · mixture specification
Developer patent
Morozov VG, Khavinson VK. US Patent 5,070,076, granted 1991.
The patent describes a calf-thymus preparation as peptide fractions across roughly 600 to 6,000 Da with process and physicochemical characteristics. It provides no clinical efficacy data or independent batch verification.
- Study design
- Granted composition and process patent
A patent is not a clinical trial, regulator assay, or proof that a current vial matches the claimed process.
Read the original sourceClinicalTrials.gov/WHO aliases · zero exact records
Trial registrations
ClinicalTrials.gov.
ClinicalTrials.gov lists no exact-name Thymalin intervention study. Older Russian-language clinical reports without matching registrations remain separate evidence.
Read the original sourceFour-donor cell study · in vitro cytokines
Human-cell laboratory study
Linkova N et al. International Journal of Molecular Sciences, 2023.
Peripheral blood mononuclear cells from four donors were exposed to thymalin and two named dipeptides. Several inflammatory outputs changed in vitro. No donor received thymalin and the experiment cannot establish a clinical immune effect.
- Participants / model
- Cultured blood cells from 4 human donors
- Treatment
- Laboratory thymalin, Lys-Glu, and Glu-Trp exposure
- Study design
- In vitro human-cell experiment
Cell study · extract diverged from peptides
In vitro comparative study
Avolio F et al. International Journal of Molecular Sciences, 2022.
Four defined peptides reduced monocyte adhesion in the assay, while the heterogeneous thymalin extract increased it and differed on other cellular outputs. The result demonstrates that named fractions cannot stand in for the parent extract.
- Treatment
- Thymalin extract and four defined peptides in THP-1 cells
- Study design
- Replicated in vitro comparative experiment
Russian animal study · sensitization signal
Russian-language animal study
Суходоева ГС et al. Журнал микробиологии, эпидемиологии и иммунобиологии, 1993.
The Russian-language animal report describes increased sensitization to a microbial antigen after thymalin, with repeated injections producing a stronger effect than a single exposure. It is a heterologous animal-protein extract signal in guinea pigs, not a measured human adverse-event rate.
- Participants / model
- Guinea pigs
- Treatment
- Single or repeated thymalin exposure with microbial antigen challenge
- Study design
- Animal immunogenicity experiment
Defined Glu-Trp fraction · phase 3 negative
Randomized double-blind placebo-controlled trial of a related fraction
Noy A et al. Journal of Clinical Oncology, 2005.
In 202 participants, response was 23% with IM862 and 21% with placebo (P=.46). Median time to progression was 16 versus 35 weeks (P=.012), although the active arm had less concurrent antiretroviral therapy. This tested defined Glu-Trp, not the parent thymalin extract.
- Participants / model
- 202 people with AIDS-related Kaposi sarcoma
- Treatment
- Intranasal IM862 or placebo
- Follow-up
- 24 weeks
- Study design
- Randomized double-blind phase 3 trial
The negative Glu-Trp trial does not establish the parent extract's efficacy or inefficacy; earlier uncontrolled fraction signals do not establish a Thymalin effect.
Read the original sourceUS, EU, and historical Soviet status
Regulatory status
FDA, EMA, and a developer-authored history of Thymalin.
The cited US and EU records contain no Thymalin approval. A developer-authored account reports USSR registration certificate 82/1108/8 under Ministry of Health Order 1108 dated November 10, 1982.
The 1982 registration is supported by a developer-authored account rather than the original certificate and does not imply US or EU approval.
Read the original sourceWhy is Thymalin in D tier?
The D grade reflects uncertain extract composition, an old developer-led unregistered clinical record, and no independent confirmation of the reported mortality result.