FDA Gives Go-Ahead to Phase 3 Trial of Nilotinib for Alzheimer Disease
The Food and Drug Administration (FDA) has accepted an Investigational New Drug (IND) application for a Phase 3 trial (NCT number TBD) to evaluate the efficacy and safety of nilotinib (KeifeRx, Washington, DC) for dementia caused by Alzheimer disease (AD). Nilotinib is an antineoplastic drug approved for the indication of Philadelphia chromosome-positive chronic myeloid leukemia in adults, under the brand name Tasigma (Novartis, East Hanover, NJ).
Nilotinib is a tyrosine kinase inhibitor with multiple effects on downstream second messenger systems that effectively reduces protein misfolding and aggregation, including amyloid β (Aβ, tau, and a-synuclein in animal models of neurodegeneration. Results of a small phase 2 trial (NCT02947893; n=37) published in Annals of Neurology showed a significant difference in Aβ in the frontal lobes of participants with mild-to-moderate AD treated with nilotinib vs placebo. There was no significant difference between drug and placebo groups for whole brain amyloid, however. Those treated with nilotinib had decreases in frontal lobe Aβ, whereas those treated with placebo had increases in Aβ. Cerebrospinal fluid (CSF) Aβ42 and phosporylated tau levels were reduced with niliotinib treatment and hippocampal volume loss was decreased.
The planned phase 3 trial will be a placebo-controlled, double-blind study in 1,275 participants who have early AD, who will be randomly assigned to receive to receive1 of 2 different doses of nilotinib or placebo for 72 weeks.
“We are excited about this major milestone for KeifeRx, and the chance to demonstrate the capabilities of our tyrosine kinase inhibitors platform in neurodegeneration,” said Chris Hoyt, CEO, KeifeRx. “We are looking forward to the successful execution of this program and the ability to help people affected by such a debilitating disease.”
A biomarker substudy will investigate effects of the drug on the amyloid brain burden as well as other markers of AD pathology.