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., 2014; Park 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., 2018; Kim et al., 2018; Lee et al., 2020; Kwon 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.