Key papers ✓ 5✗ 3? 3

• ✗ Negative human RCTJ Clin Oncol · 2005

  Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: from the AIDS Malignancy Consortium and IM862 Study Team.

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind24 weeks

  Randomized, double-blinded, placebo-controlled phase III trial of IM862 (dipeptide L-Glu-L-Trp), 5 mg intranasally every other day

  Phase III placebo-controlled trial of intranasal IM862 (L-Glu-L-Trp) in 202 people with AIDS-related Kaposi's sarcoma: response rate 23% vs 21% on placebo, and time to progression was shorter with IM862 (16 vs 35 weeks).

  Key resultResponse rate 23% with IM862 vs 21% with placebo (P = .46); median time to progression 16 vs 35 weeks (P = .012)

  Study details

  Studied

  HIV-positive patients with AIDS-related Kaposi's sarcoma

  Compared with

  Placebo

  Main outcome

  Tumor response rate

  Sample

  202 HIV-positive patients enrolled: 104 on IM862, 98 on placebo

  Authors' conclusion

  IM862 was not superior to placebo and may accelerate time to progression. Antiretroviral therapy alone gave substantial sustained responses and may have confounded earlier estimates.

  Limitations

  Antiretroviral use differed between arms (88% vs 96%); IM862 is the thymogen-related dipeptide, not thymogen itself.

  DOI 10.1200/JCO.2005.11.043PubMed 15598977
• ✗ Negative human RCTProstate · 2007

  Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies.

  Humans71 evaluable patients (34 IM862, 37 placebo)RandomizedPlacebo-controlledDouble-blind6 months or until progression

  Double-blind randomized placebo-controlled trial during intermittent androgen ablation

  Double-blind phase II trial in 71 men with recurrent prostate cancer: IM862 did not delay PSA progression vs placebo (41% vs 49% progressed at 6 months, p=0.39); well tolerated.

  Key resultAt 6 months disease progressed in 14 (41%) of 34 on IM862 vs 18 (49%) of 37 on placebo (P = 0.39)

  Study details

  Studied

  Men with prostate cancer and rising PSA after prostatectomy and/or radiation

  Compared with

  Placebo

  Main outcome

  Time to PSA progression

  Authors' conclusion

  IM862 was well tolerated but failed to show superiority over placebo in prolonging time to PSA progression; the design was an efficient platform for drug screening.

  Limitations

  Small trial.

  DOI 10.1002/pros.20649PubMed 17879948
• ✓ Positive human RCTAdv Gerontol · 2011

  [Application thymogen for preoperative preparation of elderly patients with tumor processes in abdominal cavity].

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind7 days before surgery

  Double-blind, randomized, placebo-controlled study of Thymogen 100 mg intranasally once daily

  Russian double-blind, placebo-controlled study in elderly patients before abdominal tumor surgery: 7 days of intranasal thymogen restored cellular immune measures and reduced postoperative complications; patient numbers not stated in abstract.

  Study details

  Studied

  Elderly patients undergoing surgery for solid tumors in the abdominal cavity and retroperitoneal space

  Compared with

  Isotonic sodium chloride placebo

  Main outcome

  Cellular immunity parameters, postoperative complications, postoperative period

  Authors' conclusion

  Preoperative Thymogen helped restore cellular immunity parameters and significantly decreased postoperative complications and shortened the postoperative period.

  Limitations

  Abstract gives no sample size or numerical results.

  PubMed 21957588
• ? Inconclusive human RCTJ Clin Oncol · 2000

  Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma.

  Humanssize not reportedRandomizedPlacebo-controlledRepeated cycles until progression or toxicity

  Randomized comparison of two IM862 5 mg intranasal dosing schedules

  Randomized comparison of two IM862 dosing schedules (no placebo) in 44 people with AIDS-related Kaposi's sarcoma: 36% had major responses, but most were also on new HIV therapy, which the later phase III trial showed could explain responses.

  Key resultMajor responses in 36% (five complete and 11 partial remissions)

  Study details

  Studied

  Patients with AIDS-related Kaposi's sarcoma (median age 38 years)

  Compared with

  Two dosing schedules (no placebo)

  Main outcome

  Tumor response

  Sample

  44 patients randomized to two schedules (18 five-days-on/off, 26 every-other-day)

  Authors' conclusion

  Intranasal IM862 was well tolerated and had antitumor activity in AIDS-KS; a randomized double-blinded study was in progress.

  Limitations

  No placebo arm; most patients on concurrent protease inhibitors.

  DOI 10.1200/JCO.2000.18.4.716PubMed 10673512
• ✗ Negative human trialBr J Cancer · 2004

  Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.

  Humans25 peopleNo control group8-week cycles

  Prospective phase II trial, IM862 20 mg intranasally three times daily

  Phase II single-arm trial in 25 patients with metastatic kidney cancer: IM862 produced no objective responses (8 stable, 17 progressed), with no significant toxicity.

  Key result8 patients had stable disease and 17 progressed; median survival 7.9 months; median time to progression 1.9 months

  Study details

  Studied

  Patients with metastatic renal cell carcinoma

  Main outcome

  Objective response

  Sample

  25 patients accrued

  Authors' conclusion

  IM862 had no toxicity but no significant objective responses in metastatic RCC and should not be further evaluated as a single agent at these doses. The fall in VEGF warrants further investigation.

  Limitations

  Single-arm phase II; no comparator.

  DOI 10.1038/sj.bjc.6602126PubMed 15354209Free full text
  Figure 1
• ? Inconclusive human trialProbl Tuberk · 1994

  [Changes of immune and non-specific reactivity in patients with chronic suppurative obstructive bronchitis in comprehensive treatment with thymogen].

  Humans33 peopleNo control group

  Thymogen added to multimodality treatment

  Controlled study of 33 patients with chronic suppurative bronchitis: adding thymogen to treatment normalized several T-cell and non-specific immune measures, with authors reporting higher clinical efficacy.

  Study details

  Studied

  Patients with chronic pyoobstructive bronchitis with immunological disorders

  Main outcome

  T-cell immunity and nonspecific responsiveness parameters

  Sample

  33 patients

  Authors' conclusion

  Thymogen in multimodality treatment contributed to normalization of T-cell immunity and nonspecific responsiveness, with higher clinical efficacy.

  Limitations

  Abstract describes no control group.

  PubMed 7984617
• ✓ Positive animalBiogerontology · 2000

  Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats.

  Animalssize not reportedRandomized12 months of treatment, followed to natural death

  Randomized, saline-controlled; L-Glu-L-Trp 5 micrograms/rat s.c. 5 times per week

  In 76 female rats injected for 12 months, L-Glu-L-Trp did not change mean lifespan but extended survival of the longest-lived 10% and reduced total and malignant tumor incidence.

  Key resultLife span of longest-lived 10% was 1048 days vs 949 in controls (P < 0.001); total tumor incidence 1.5 times lower (P < 0.01)

  Study details

  Studied

  Five-month-old outbred female rats

  Compared with

  Saline

  Main outcome

  Life span, aging rate, spontaneous tumor incidence

  Sample

  76 female rats: 32 controls, 44 dipeptide-treated

  Authors' conclusion

  L-Glu-L-Trp delayed the aging rate and decreased spontaneous tumor incidence in rats. Mean life span did not differ between groups.

  Limitations

  Rat study; mean life span was similar in both groups.

  DOI 10.1023/a:1010042008969PubMed 11707921
• ✓ Positive animalInt J Cancer · 2003

  Natural killer cell cytolytic activity is necessary for in vivo antitumor activity of the dipeptide L-glutamyl-L-tryptophan.

  Animalssize not reported

  In vivo mouse tumor studies in NK-deficient, perforin, IFN-gamma and IL-12 knockout mice

  L-Glu-L-Trp inhibited tumor growth in mice without direct toxicity to tumor cells; the effect required natural killer cell activity.

  Study details

  Studied

  Mice (including gene-knockout strains) with tumors, and human tumor cell lines

  Main outcome

  Antitumor activity of L-glu-L-trp

  Authors' conclusion

  L-glu-L-trp antitumor activity in mice depends on cytolytic NK or NKT cell activity and perforin; it is independent of IFN-gamma and partly dependent on IL-12.

  Limitations

  Mouse study.

  DOI 10.1002/ijc.11253PubMed 12845648
• ✓ Positive human RCTArkh Patol · 2023

  [Repair stimulator alpha-glutamyl-tryptophan in the complex therapy of chronic atrophic gastritis: results of histological examination].

  Humans116 peopleRandomizedPlacebo-controlledDouble-blind

  Multicenter double-blind randomized placebo-controlled study (histology analysis)

  Multicenter double-blind placebo-controlled RCT biopsy analysis in 116 patients with H. pylori-associated chronic atrophic gastritis: alpha-glutamyl-tryptophan (same dipeptide as thymogen) increased gastric gland number 26.1% vs baseline (p=0.028) and vs placebo (p=0.026).

  Key resultGlands per 1 mm2 rose 26.1% vs baseline (p=0.028) and differed from placebo (p=0.026)

  Study details

  Studied

  Patients with Helicobacter pylori-associated chronic atrophic gastritis

  Compared with

  Placebo

  Main outcome

  Gastric gland density, parietal cells, intestinal metaplasia, CXCL-12 and CDX-2 expression

  Sample

  116 patients with biopsies analysed

  Authors' conclusion

  The authors found a significant positive effect on regenerative mechanisms and histology of the atrophic gastric mucosa versus baseline and placebo.

  Limitations

  Histology sub-analysis; drug is a marketed alpha-Glu-Trp product; duration and doses not given in abstract.

  DOI 10.17116/patol20238503154PubMed 37272441
• ✓ Positive human RCTTer Arkh · 2023

  [Endoscopic and morphometric analysis of the reduction of acute inflammatory process in the gastric mucosa after therapy with Regasthym Gastro].

  Humans80 peopleRandomizedPlacebo-controlledDouble-blind

  Retrospective analysis of a double-blind placebo-controlled study (gastroscopy + morphometry)

  Double-blind placebo-controlled study (retrospective analysis) in 80 patients with H. pylori-associated chronic atrophic gastritis (43 alpha-Glu-Trp product vs 37 placebo): less mucosal edema (p=0.008) and lower overall endoscopic inflammation score (p=0.006).

  Key resultDecrease in edema (p=0.008) and total acute-inflammation signs (p=0.006); fewer negative-dynamics outcomes (p=0.038)

  Study details

  Studied

  Patients with H. pylori-associated chronic atrophic gastritis in exacerbation

  Compared with

  Placebo

  Main outcome

  Endoscopic inflammation score and inflammatory cells per mm2 of mucosa

  Sample

  80 patients (43 drug, 37 placebo)

  Authors' conclusion

  The authors conclude the drug significantly reduces inflammation on gastroscopy and morphometry and recommend adding it to complex therapy of chronic gastritis.

  Limitations

  Retrospective analysis of a trial; marketed alpha-Glu-Trp product (Regasthym Gastro); added to other therapy.

  DOI 10.26442/00403660.2023.04.202147PubMed 38158980
• ? Inconclusive human trialRussian-languageВестник Авиценны · 2008

  Эффективность тимогена и кларитина в комплексном лечении больных крапивницей

  Humans79 peopleNo control group

  Uncontrolled treatment series (no control group described in abstract)

  Russian-language study of 79 patients with urticaria given thymogen plus the antihistamine Claritin: remission over 6 months in 25% and over 3 months in 43%, with improved immune indices; no control group described, so thymogen's own effect cannot be separated.

  Key resultRemission over 6 months in 25% of patients and over 3 months in 43%

  Study details

  Studied

  Patients with urticaria and reduced T-suppressor/T-helper levels and raised IgE

  Main outcome

  Remission duration and immune indices

  Sample

  79 patients with urticaria

  Authors' conclusion

  The authors report that the thymogen and Claritin regimen produced long remissions and improved immune indices.

  Limitations

  No control group; combined with an antihistamine, so the effect of thymogen cannot be isolated.

  CyberLeninka (Russian)

Reported side effects

• reportedHeadache, fatigue, tingling, nausea (mild, transient) [ref]
• reportedFaster tumor progression vs placebo in Kaposi's sarcoma [ref]

Western IM862 trials reported the dipeptide as well tolerated, with only mild transient symptoms; Russian thymogen studies report no complications but give little safety detail.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.