Among patients with progressive supranuclear palsy (PSP), treatment with tilavonemab did not affect progression of the disorder and the phase 2 study was terminated after a prespecified interim futility analysis, as reported in Lancet Neurology.
Because no drugs have been approved for PSP, its 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 objective of the current study was to investigate the safety and efficacy of tilavonemab in adults. The phase 2, multicenter, randomized, placebo-controlled, double-blind study included adults from 66 centers who were aged 40 years and older with possible or probable PSP. All study participants had symptoms for less than 5 years and could walk 5 steps with minimal assistance.
The patients were randomly assigned to 3 groups: tilavonemab 2000 mg, tilavonemab 4000 mg, or a matching placebo. Participants received infusions on days 1, 15, and 29, and every 28 days through to the end of the 52-week treatment period.
The change in the Progressive Supranuclear Palsy Rating Scale total score from baseline to week 52 in the intention-to-treat population was the primary endpoint.
The interim analysis included 377 participants who received at least 1 dose of study drug, including 126 participants treated with tilavonemab 2000 mg, 125 patients treated with tilavonemab 4000 mg, and 126 patients who received placebo.
Change from baseline in Progressive Supranuclear Palsy Rating Scale total score was similar between treatment groups in all visits up to week 52. At week 52, the least squares mean 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 during the study period in 111 (88%) participants in the tilavonemab 2000 mg group, 111 (89%) patients in the tilavonemab 4000 mg group, and 108 (86%) in the placebo group. Serious adverse events occurred in 23%, 27%, and 26% of participants, respectively.
Falls were the most common treatment-emergent adverse event, reported in 33% of patients treated with 2000 mg, 43% of those in the tilavonemab 4000 mg group, and 39% in the placebo group. Falls were also the most common treatment-emergent serious adverse event reported in 4%, 5%, and 5% of patients, respectively.
Additional common treatment-emergent adverse events included contusions (13%, 19%, and 14%, respectively), and skin lacerations (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, no deaths were considered to be related to the study drug.
The statistical power being restricted by early termination was the main limitation of the study.
“Results from our study provide important information on the trajectory of clinical and biomarker endpoints in individuals with progressive supranuclear palsy that could help to guide further investigations of tau-directed therapies in progressive supranuclear palsy,” concluded the study researchers.
Disclosure: This research was supported by AbbVie. Please see the original reference for a full list of authors’ disclosures.
Höglinger GU, Litvan I, Mendonca N, et al. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. Lancet Neurol. 2021;20(3):182-192. doi:10.1016/S1474-4422(20)30489-0