Tilavonemab not effective in progressive supranuclear palsy

In patients with progressive supranuclear palsy (PSP), treatment with tilavonemab had no effect on progression of the disorder, and the Phase 2 study was discontinued after a pre-determined preliminary futility analysis, as reported in Lancet Neurology.

Since no drugs have been approved for PSP, treatment is limited to symptomatic therapies. Tilavonemab, a monoclonal antibody that binds to the N-terminus of human tau, showed promising results in transgenic mice expressing mutated human tau.

The aim of the current study was to investigate the safety and effectiveness of tilavonemab in adults. The phase 2, multicenter, randomized, double-blind, placebo-controlled study enrolled adults from 66 centers who were 40 years of age and older and who may or may have PSP. All study participants had symptoms for less than 5 years and were able to walk 5 steps with minimal assistance.

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The patients were randomly divided into 3 groups: tilavonemab 2000 mg, tilavonemab 4000 mg or a suitable placebo. Participants received infusions on days 1, 15, and 29, and every 28 days until the end of the 52-week treatment period.

The change in total score on the Progressive Supranuclear Palsy Rating Scale from baseline to week 52 in the treated population was the primary endpoint.

The interim analysis included 377 participants who received at least 1 dose of the study drug, including 126 participants treated with tilavonemab 2000 mg, 125 patients treated with tilavonemab 4000 mg and 126 patients treated with placebo.

The total score on the progressive supranuclear palsy rating scale from baseline was similar between treatment groups for all visits through week 52. At Week 52, the mean least square change from baseline was similar in all groups and was 10.5 for tilavonemab 2000 mg, 11.4 for tilavonemab 4000 mg, and 10.5 for placebo.

The safety profile was similar in all treatment groups: at least 1 adverse event was reported in 111 (88%) subjects in the tilavonemab 2000 mg group, 111 (89%) subjects in the tilavonemab 4000 mg group, and 108 (86%) during the study period in the placebo group. Serious adverse events occurred in 23%, 27% and 26% of the participants, respectively.

Falls were the most common treatment-related adverse event reported in 33% of patients treated with 2000 mg, 43% of patients in the 4000 mg tilavonemab group, and 39% in the placebo group. Falls were also the most common treatment-related serious adverse event reported in 4%, 5% and 5% of patients, respectively.

Other common treatment-related adverse events were bruises (13%, 19% and 14%, respectively) and skin injuries (15%, 17% and 15%, respectively).

During the study period, 26 (7%) patients died, including 9 (7%) in the tilavonemab 2000 mg group, 9 (7%) in the tilavonemab 4000 mg group and 8 (6%) in the placebo group. However, it was not believed that any deaths were related to the study drug.

The statistical power that was limited by early termination was the main limitation of the study.

“The results of our study provide important information about the progression of clinical endpoints and biomarker endpoints in people with progressive supranuclear palsy that could help further investigate tau-directed therapies for progressive supranuclear palsy,” concluded the study researchers.

Disclosure: This research was supported by AbbVie. For a full list of the authors’ information, see the original reference.


Höglinger GU, Litvan I., Mendonca N. et al. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a randomized, placebo-controlled phase 2 study. Lancet Neurol. 2021; 20 (3): 182-1. 192. doi: 10.1016 / S1474-4422 (20) 30489-0

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