Long-term Safety and Clinical Effects of Nilotinib in Parkinson’s Disease
Fernando Pagan1, Yasar Torres-Yaghi1, Michaeline Hebron2, Jaeil Ahn2, Charbel Moussa2
1Georgetown University Hospital, 2Georgetown University
Nilotinib is FDA-approved for leukemia and this open label study investigated the safety, tolerability and potential clinical effects of nilotinib in medically optimized Parkinson’s disease patients. 
Safety and tolerability were primary objectives and clinical outcomes were exploratory.
Sixty-three patients completed a 15-month Phase 2, double-blind, placebo-controlled study and were re-randomized 1:1 into an open label study of nilotinib, 150mg versus 300mg, for 12 months.
Nilotinib was safe and tolerated, no adverse effects seemed to be related to the drug and no differences in adverse events were observed between groups. Exploratory clinical outcomes showed that nilotinib, 300mg, was remarkably stable from baseline to 27 months using partial and total UPDRS. Nilotinib, 150mg versus 300mg, significantly declined using partial or the sum of UPDRS I and II. There was no significant difference in nilotinib, 150mg versus 300mg, using UPDRS III (ON Levodopa) and total UPDRS I-III. Sub-group analysis showed that late start nilotinib, 150mg, significantly worsened using the sum of UPDRS II+III and total UPDRS I-III compared to late start nilotinib, 300mg. Quality of life using PDQ-39 in nilotinib, 150 mg, significantly declined between 15 and 27 months compared to nilotinib, 300 mg, and there was no change in cognition using MoCA between groups. 

This study provides evidence that nilotinib is safe and tolerated in Parkinson’s disease. The exploratory clinical data will inform an adequately powered larger study to evaluate the efficacy of nilotinib, 300mg, in PD.