New data from a Phase 2a clinical trial assessing GV1001 (GemVax) in progressive supranuclear palsy (PSP) revealed that while the primary endpoint was not met, subgroup analyses of specific PSP subtypes showed promising results, paving the way for a global Phase 3 trial. The 24-week, randomized, double-blind, placebo-controlled study presented at Neuro2024, indicated a potential for GV1001 to become the first treatment option for PSP.
Phase 2a Trial Results
The Phase 2a trial (NCT05819658) involved 78 patients with PSP across five centers in Korea. Participants were randomly assigned to receive either placebo or GV1001 at doses of 0.56 mg or 1.12 mg, administered subcutaneously. The primary endpoint was the change in PSP-Rating Scale score. After 24 weeks, the GV1001 0.56 mg dose group showed a 2.14-point deterioration compared to a 4.10-point change in the placebo group, representing a 48% reduction in disease progression. This exploratory study aimed to determine the optimal dosage and understand the peptide's effects on various subgroups.
Hyungsik Moon, chief scientific officer at GemVax, stated, "Although the topline result did not achieve statistical significance, the evidence is strong enough to consider moving forward to a pivotal trial and shows potential to develop GV1001 as the world's first treatment option for PSP."
Subgroup Analysis: PSP-RS
The study included patients with PSP-parkinsonian and PSP-Richardson’s syndrome (PSP-RS). A subgroup analysis focused on PSP-RS patients, who typically have greater tau protein accumulation. After 24 weeks, the GV1001 0.56 mg treatment group showed a 0.25-point deterioration on the PSP-Rating Scale compared to a 5.19-point deterioration in the placebo group. This 4.94-point difference represents a 95% reduction in disease progression in PSP-RS patients.
Responder Rate
A significant proportion of PSP-RS patients in the treatment group demonstrated either symptom stabilization or improvement. The responder rate, defined as the percentage of patients whose PSP Rating Scale scores improved or remained stable after six months, was 58.33% in the GV1001 0.56 mg group.
Expert Commentary
Gunter Höglinger, MD, head of the department of neurology at LMU Hospital in Munich, commented, "Very exciting Phase 2 level data with novel drug study with new mechanisms of action. Data is preliminary but very promising and it is in line with [GV1001] Alzheimer's disease clinical data. I look forward to further development and very excited to participate and lead the [PSP] Phase 3 study."
GV1001: A Telomerase-Derived Peptide
Originally developed as a cancer vaccine, GV1001 is a 16-amino-acid peptide derived from human telomerase reverse transcriptase (TERT). It is also under investigation in a Phase 2 study for Alzheimer's disease (AD), expected to conclude in 2026. This multicenter, randomized, double-blind, placebo-controlled study involves 180 patients with mild to moderate AD, receiving either GV1001 (0.56 or 1.12 mg) or placebo subcutaneously. The primary endpoint is the change in the Alzheimer’s Disease Assessment Scale-cognitive subscale.
Previous Alzheimer's Disease Study
GV1001 was previously assessed in a Phase 2 study (NCT03184467) involving patients with moderate-to-severe AD. Results published in 2021 indicated that the 1.12 mg dose showed less decrease in Severe Impairment Battery (SIB) score at 12 and 24 weeks compared to placebo (P < 0.05).
