South Korean biopharmaceutical company GemVax & Kael announced in late October topline results from its phase 2a clinical trial evaluating a drug for PSP. While the drug failed to show significant efficacy, the results showed enough promise that the company hopes to proceed to phase 3 trials.

PSP, or progressive supranuclear palsy, is an FTD disorder primarily associated with movement symptoms. PSP has several known subtypes, such as the most common forms, PSP-Richardson’s syndrome (PSP-RS) and PSP-Parkinson’s (PSP-P). Like the fellow movement-based FTD disorder corticobasal degeneration (CBD), PSP is primarily associated with dysfunction of the tau protein, which causes it to form abnormal accumulations in affected areas of the brain.

Prior research on GemVax’s drug, GV1001, found it reduced disease-associated forms of tau in mouse models of Alzheimer’s disease. In the phase 2a trial, which was comprised of people with PSP-RS and PSP-P to participate, participants randomly received a .56 mg dose, a1.12 mg dose, or a placebo administered via injection once weekly for one month, followed by 2-week intervals for five months. The endpoint of the trial — a measurable outcome that helps determine if the intervention being studied works — was whether GV1001 impacted disease progression in the test groups, as reflected by a lower mean PSP-Rating Scale score than that of the control group.

According to GemVax, participants in all three groups experienced disease progression, though there was a 48% reduction in progression for the .56 mg group. While a statistically significant result has not been demonstrated, the results show promise for GV1001 as a treatment for PSP.

Point increase in the mean PSP-Rating Scale score per dose:

• .56 mg dose = 2.14 point increase.
• 12 mg dose = 6.46 point increase.
• Placebo dose = 4.10 point increase.

When reviewing the differences in scores between people with different PSP subtypes, GemVax said that people with PSP-RS had significantly lower PSP Rating Scale scores than the control group. The mean increase of the PSP-RS group’s score was .25, a 95% decrease in disease progression compared to the 4.10 increase of the control group. The company noted that PSP-RS participants experienced stabilization of their symptoms or even improvement of their symptoms during the trial.

In addition to showing promising results, the safety data on GV1001 was consistent with previously gathered data. Researchers noted no serious adverse effects, and the drug generally well tolerated by participants.

“This Phase 2a trial was an exploratory study to determine the optimal dosage and find out how the peptide works on different subgroups,” said GemVax CSO Hyungsik Moon. “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.”

Presenting trial findings at the Neuro2024 PSP and CBD International Research Symposium, GemVax received positive feedback from experts in attendance. Scientists from industry and academic organizations expressed excitement about the drug entering phase 3 trials.

“This pilot study was not fully powered, and the treatment duration with 6 months was short,” said Peter Schüler, MD, Senior Vice President of Drug Development at global CRO ICON. “Thus, statistically significant confirmatory results could not be expected. Nonetheless, the observed trends are very plausible and consistent in two domains: motor performance and cognitive function, both favoring the lower dose group. The trial identified the optimal dose, which was one of the primary objectives of the Phase 2a study, and demonstrated clinically meaningful benefits, namely full stabilization of the disease compared to the placebo group.”

Even when trials end unsuccessfully, however, as when Wave Life Sciences discontinued their clinical trial for genetic FTD in 2023, they can further FTD science and provide crucial insights into the interactions between different interventions and FTD disorders. Wave Life Sciences provided insights into using a specific type of drug known as an antisense oligonucleotide.