Rare Disease Report

Pivotal Clinical Trial Shows Davunetide Ineffective For Treating Progressive Supranuclear Palsy

MAY 28, 2014
RDR Staff

The clinical trial that led to Allon Therapeutics filing for bankruptcy has finally been published. From a financial perspective it is troubling that one study can lead to the downfall of a company but from a clinical science perspective, the publication illustrates the importance of sharing information to better understand a disease (progressive supranuclear palsy) and to develop future clinical trials.
The study was a large, pivotal randomized, double-blind, placebo-controlled phase 2/3 trial examining the safety and efficacy of davunetide in patients with progressive supranuclear palsy.
Patients were randomized to receive davunetide (30 mg twice daily, intranasally; n=157) or placebo (n=156) for 52 weeks at 48 centers in Australia, Canada, France, Germany, United Kingdom, and United States.
The primary endpoints were the change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) and Schwab and England Activities of Daily Living (SEADL) scale at up to 52 weeks.
And the results were very sobering. After one year of treatment, the davunetide and placebo groups did not differ in the change from baseline in PSPRS (median 11.8 [95% CI 10.5 to 13.0] vs 11.8 [10.5 to 13.0], respectively, p=0.41) or SEADL (–0.20 [–0.20 to –0.17] vs –0.20 [–0.22 to –0.17], respectively, p=0.92).
In their discussion, the authors stated  “The groups were well matched at baseline, and the primary outcome measures PSPRS and SEADL showed the expected yearly changes in both groups, suggesting that the study was adequately powered to detect a treatment effect of davunetide if one had existed.” 
In a commentary accompanying the study publication, Pierre Tariot wrote that while the study results were negative, the clinical trial “sets a precedent for future studies with the operational lessons learned, infrastructure development, outreach to patients, and accrual of substantial longitudinal clinical and biomarker data that should be helpful for designing future trials.”

About Progressive Supranuclear Palsy

Progressive supranuclear palsy is a rare brain disorder that causes serious and progressive problems with control of gait, balance, complex eye movement, and cognition. One of the classic signs of the disease is an inability to aim the eyes properly due to damage to the supranuclear region of the brain.
There is currently no effective treatment for progressive supranuclear palsy and current treatment strategies may include antidepressants, levodopa, special glasses and/or weighted walking aids.


Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014. [Epub ahead of print] doi:10.1016/S1474-4422(14)70088-2

Tariot P.  When should neuroprotective drugs move from mice to men? Lancet Neurol. 2014. [Epub ahead of print] doi:10.1016/S1474-4422(14)70112-7

Micrograph of tau staining in patient diagnosed with progressive supranuclear palsy courtesy of wikimedia commons.

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