To present results from a phase 2 study investigating the efficacy and safety of a humanized anti-tau monoclonal antibody (tilavonemab [ABBV-8E12]) for treatment of progressive supranuclear palsy (PSP).

PSP is a progressive, ultimately fatal movement disorder associated with tau protein abnormalities. There are no approved PSP treatments. Therapeutic strategies focus on symptom management. In transgenic mice, anti-tau antibody treatment resulted in reduced brain volume loss, reduced tau pathology progression, and increased cognitive performance.

This phase 2, multiple-dose, multicenter, randomized, double-blind, placebo-controlled study (NCT02985879) consisted of an 8-week screening period, 52-week treatment period, and 20-week follow-up. Patients were randomized 1:1:1 to receive 4000 mg tilavonemab, 2000 mg tilavonemab, or placebo via 3- to 4-hour intravenous infusion on days 1, 15, 29, and for every 28 days thereafter. Eligible patients were aged ≥40 years, had PSP symptoms <5 years, had a reliable study partner, and could walk 5 steps with minimal assistance. The primary efficacy outcome was change from baseline to week 52 in the PSP rating scale (PSPRS). Treatment-emergent adverse events (TEAEs) were monitored throughout the study.

Of 378 randomized patients, 151 could complete treatment (placebo, n = 51; 2000 mg, n = 52; 4000 mg, n = 48), as the study was terminated prematurely. At week 52, disease burden worsened in all groups. Least squares mean (standard error) increase from baseline in PSPRS total score was 10.4 (1.0), 10.5 (1.0), and 11.4 (1.0) points for placebo, 2000 mg, and 4000 mg, respectively. There were no significant differences between treatment groups (P > .05). The most common TEAEs were falls (38.5%), skin lacerations (15.4%), and contusions (15.1%), consistent with underlying disease.

Although tilavonemab was generally well tolerated, it failed to show efficacy for PSP treatment. Biomarker analyses in PSP patients treated with tilavonemab are ongoing.