Therapeutics

GV1001

Tools

Back to the Top

Overview

Name: GV1001
Synonyms: RIAVAXTM, Tertomotide
Therapy Type: Immunotherapy (active) (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3)
Company: GemVax & KAEL Bio
Approved for: Pancreatic cancer (Korea)

Background

Originally developed as a cancer vaccine, GV1001 is a 16-amino-acid peptide comprising a sequence from the human enzyme telomerase reverse transcriptase (TERT). Most cancers highly express TERT, and immunization with GV1001 aims to activate the immune system to recognize and kill cancer cells. GV1001 was approved in Korea for immunotherapy of pancreatic cancer, but failed to show efficacy in two international pancreatic cancer trials (Middleton et al., 2014; Clinicaltrials.gov).

The peptide reportedly penetrates cells, interacts with HSP70 and HSP90, and displays direct anti-cancer and anti-viral activity independent of an immune response (Kim et al., 2018; Kim et al., 2016).

In non-cancer cells, GV1001 has anti-inflammatory and antioxidant activity. In rat neuronal stem cells, GV1001 blocked Aβ oligomer-induced toxicity, and increased survival of cells exposed to oxidative stress (Park et al., 2014Park et al., 2016). The authors attribute these actions to GV1001’s ability to mimic TERT’s antioxidant, anti-apoptotic, and pro-survival functions.

Beneficial effects have been reported in rodent models of hearing loss, macular degeneration, and stroke (Kim et al., 2018Kim et al., 2018Lee et al., 2020Kwon et al., 2021).

Findings

In 2017, GemVax and Kael began a Phase 2 trial to assess safety and efficacy of GV1001 in people with moderate to severe Alzheimer’s disease at 13 sites in Korea. The study enrolled 96 clinically diagnosed patients, who were randomized equally to receive four weekly subcutaneous injections of 0.56 mg or 1.12 mg of GV1001, or placebo, followed by biweekly injections for 24 weeks, for a total of 14 injections. All participants were taking donepezil. The primary outcome at 24 weeks was change on the Severe Impairment Battery; secondary outcomes included the Korean-MMSE and standard measures of cognition and function, i.e., the CDR-SB, Neuropsychiatric Inventory, Global Deterioration Scale, ADCS-Activities of Daily Living and Clinician Interview-Based Impression of Change.

The company presented top-line trial results at CTAD 2019 (Dec 2019 conference news). The study met its primary endpoint, with treated participants holding steady on the SIB (0.12 point drop) whereas those on placebo dropped by 7.23 points. A dose response was not shown; results for secondary endpoints were not shown. Adverse events were similar across all three groups. Results were subsequently published after peer review (Koh et al., 2021). In the full analysis, only the higher-dose group met the primary endpoint. They declined 0.3 points on the SIB compared to 6.9 for the placebo group. The ADCS-ADL and CDR-SB showed a similar pattern, but did not reach statistical significance. Other secondary outcomes were negative at 24 weeks.

In May 2021, a Phase 2 trial of similar size and design as the Korean study was registered to be conducted in the U.S. According to the company, the trial was delayed by the COVID pandemic (press release). It was ultimately withdrawn in early 2022 with no patients enrolled.

Instead, in October 2022, GemVax and Kael began a larger and longer Phase 2 study, also in the U.S. It plans to randomize 180 people with mild to moderate Alzheimer’s to four weekly subcutaneous injections of 0.56 mg or 1.12 mg of GV1001, or placebo, followed by biweekly injections for one year. Participants must have an MMSE score between 13 and 24. The primary outcome will be the change on the ADAS-Cog; secondary outcomes are changes in measures of cognition and function, similar to the Korean study. Completion is anticipated in September 2024.

In March 2022, the company registered a Phase 3 study in 936 Korean patients with moderate to severe Alzheimer’s. Participants must have a Korean-MMSE of 19 or less, and will be randomized to six months of 0.56 mg or 1.12 mg GV1001, or placebo, against primary outcomes of the SIB and CDR-SB. Secondary outcomes include the Neuropsychiatric Inventory, Global Deterioration Score, and ADCS-Study Activities of Daily Living Inventory for Severe Alzheimer's Disease. A six-month open-label extension is planned, with completion slated for April 2026.

This drug has also been trialed in cancers of the prostate, lungs, liver, skin, intestine.

For details on GV1001 trials, see Clinicaltrials.gov.

Last Updated: 24 Jan 2023

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

News Citations

  1. At CTAD, Early Failures and Hints of Success, from Small Trials

Paper Citations

  1. . Efficacy and safety of GV1001 in patients with moderate-to-severe Alzheimer's disease already receiving donepezil: a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial. Alzheimers Res Ther. 2021 Mar 26;13(1):66. PubMed.
  2. . Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):829-40. Epub 2014 Jun 19 PubMed.
  3. . Anti-cancer effect of GV1001 for prostate cancer; function as a ligand of GnRHR. Endocr Relat Cancer. 2018 Oct 1; PubMed.
  4. . Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner. Sci Rep. 2016 Jul 1;6:28896. PubMed.
  5. . The novel vaccine peptide GV1001 effectively blocks β-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase. Neurobiol Aging. 2014 Jun;35(6):1255-74. Epub 2013 Dec 26 PubMed.
  6. . Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals. Neurotoxicology. 2016 Jul;55:131-141. Epub 2016 Jun 2 PubMed.
  7. . The Novel Peptide Vaccine GV1001 Protects Hearing in a Kanamycin-induced Ototoxicity Mouse Model. Otol Neurotol. 2018 Sep;39(8):e731-e737. PubMed.
  8. . Novel Peptide Vaccine GV1001 Rescues Hearing in Kanamycin/Furosemide-Treated Mice. Front Cell Neurosci. 2018;12:3. Epub 2018 Jan 19 PubMed.
  9. . A telomerase-derived peptide vaccine inhibits laser-induced choroidal neovascularization in a rat model. Transl Res. 2020 Feb;216:30-42. Epub 2019 Oct 5 PubMed.
  10. . Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury. J Stroke. 2021 Sep;23(3):420-436. Epub 2021 Sep 30 PubMed.

External Citations

  1. press release
  2. Clinicaltrials.gov
  3. Clinicaltrials.gov

Further Reading

Papers

  1. . Telomerase Biology Associations offer Keys to Cancer and Aging Therapeutics. Curr Aging Sci. 2019 Jun 20; PubMed.
  2. . Telomerase-based cancer therapeutics: a review on their clinical trials. Curr Top Med Chem. 2020 Jan 1; PubMed.
  3. . A phase II study of chemotherapy in combination with telomerase peptide vaccine (GV1001) as second-line treatment in patients with metastatic colorectal cancer. J Cancer. 2022;13(4):1363-1369. Epub 2022 Feb 14 PubMed.
  4. . A novel telomerase-derived peptide GV1001-mediated inhibition of angiogenesis: Regulation of VEGF/VEGFR-2 signaling pathways. Transl Oncol. 2022 Sep 29;26:101546. PubMed.