EPI-743 Improves Motor Function and CNS Biomarkers in PD: Results From a Phase 2A Pilot Trial

Authors

Theresa A. Zesiewicz, University of South FloridaFollow
Kevin Allison, University of South FloridaFollow
Israt Jahan, University of South FloridaFollow
Jessica A. Shaw, University of South Florida
F. Murtagh, University Diagnostic ImagingFollow
Tracy Jones, University of South FloridaFollow
Clifton Gooch, University of South FloridaFollow
Jason L. Salemi, Baylor College of MedicineFollow
Matthew Klein, Edison Pharmaceuticals, IncFollow
Guy Miller, Edison Pharmaceuticals, IncFollow
Kelly L. Sullivan, Georgia Southern UniversityFollow

Document Type

Conference Abstract

Publication Date

4-16-2016

Publication Title

Neurology

ISSN

1526-632X

Abstract

Objective: To evaluate the effects of EPI-743 in subjects with Parkinson’s disease (PD).

Background: Oxidative stress and energetic disturbances are thought to contribute to the pathogenesis of PD. EPI-743 (alpha-tocotrienol quinone) is an investigational drug targeting oxidoreductase enzymes essential for redox control of metabolism. In preclinical tests on primary cells from sporadic and mito-PD variants, EPI-743 provides protection against oxidative stress secondary to glutathione depletion.

Methods: This was a 6-month open label trial comparing 2 dose levels of orally administered EPI-743 (200 mg or 400 mg TID). Study outcomes included changes from baseline in UPDRS II and III “ON” scores, and brain metabolite levels as measured by 3T magnetic resonance spectroscopy (MRS). Wilcoxon signed rank sum tests were used in the statistical analysis.

Results: Ten subjects were enrolled in the trial (mean Hoehn and Yahr 1.5); 3 patients discontinued the study after 3 months for reasons unrelated to drug. Six of 7 patients with follow up MRS studies demonstrated a decrease in glutamine/glutamate levels in the basal ganglia opposite the side most severely affected by PD (mean decrease of 1.18 ppm to 0.74 ppm, p=0.002), signifying CNS target engagement. Clinically, subjects demonstrated an improvement in UPDRS Parts II/III, with a mean decrease from 8.1 to 6.7 (p=0.19) in UPDRS Part II and a mean decrease from 16.6 to 13.3 (p=0.17) in UPDRS Part III (n=10). EPI-743 was well tolerated with no dose-limiting toxicities or serious adverse events.

Conclusions: EPI-743 resulted in a significant decrease in CNS glutamine/glutamate levels in PD patients as well as improvements in UPDRS combined parts II and III scores, and UPDRS part III scores alone, that approached statistical significance. Treatment with EPI-743 improved an objective CNS marker of oxidative stress that correlated with clinical improvement. These positive data provide the foundation for further development of EPI-743 for PD.

Recommended Citation

Zesiewicz, Theresa A., Kevin Allison, Israt Jahan, Jessica A. Shaw, F. Murtagh, Tracy Jones, Clifton Gooch, Jason L. Salemi, Matthew Klein, Guy Miller, Kelly L. Sullivan. 2016. "EPI-743 Improves Motor Function and CNS Biomarkers in PD: Results From a Phase 2A Pilot Trial." Neurology, 86 (S16): I1.012 Vancouver, BC, Canada: American Academy of Neurology.
https://digitalcommons.georgiasouthern.edu/bee-facpubs/71