Cancer Drug Appears Safe, Shows Modest Effect on Alzheimer’s Biomarkers in Early Stage Clinical Trial

Nilotinib, an FDA-approved drug (Tasigna®) that is used to treat leukemia in children and adults, is safe and well-tolerated and may have benefits against Alzheimer’s disease according to a new clinical trial published in the Annals of Neurology. The trial was supported in part with funding from the Alzheimer’s Drug Discovery Foundation (ADDF) to Georgetown University Medical Center.

“The ADDF supported this research as part of our wider initiative to use the knowledge gained from cancer and other disease research to advance effective treatments for Alzheimer's,” said Howard Fillit, MD, the ADDF’s Founding Executive Director and Chief Science Officer. “Our diverse drug research platform includes repurposed drugs already FDA-approved for other conditions that can potentially become Alzheimer’s treatments.”

Biomarker Effect in Current Study Consistent with Earlier Nilotinib Studies

“Nilotinib had a modest effect on reducing two biomarkers of Alzheimer’s disease —hallmark proteins of the disease, beta-amyloid and tau,” said Dr. Fillit. “While the finding is encouraging and aligned with earlier research by these investigators, this a small, early study and the drug would need to be tested in a larger study to determine its safety and efficacy in treating Alzheimer’s.”

Based on lab tests that measured drug levels in the body, investigators say it appears the drug penetrated participants’ central nervous systems, which is essential for any drug intended to treat Alzheimer’s and crossed the blood-brain barrier. Investigators believe nilotinib turns on the “garbage disposal” machinery inside brain neurons (a process known as autophagy) to get rid of toxic proteins.

The amyloid burden in the participants brains, measured by PET imaging, was reduced in the nilotinib group compared to the placebo group. The nilotinib-treated group also had modest reductions in CSF levels of amyloid and phospho-tau proteins.

Nilotinib Was Safe and Well-Tolerated

The primary goal of the study was to test nilotinib’s safety. The double-blind, phase 2 trial randomly assigned 37 Alzheimer’s patients with mild dementia to receive either nilotinib or a matching placebo pill once daily for 12 months. Study participants received 150 mg a day for the first six months, with a dose escalation to 300 mg a day for the subsequent six months. In comparison, adults being treated for leukemia receive 600 mg a day in two 300 mg doses.

The drug was safe and well-tolerated, although there were more adverse events, including significantly more mood swings (agitation and irritation), at the 300 mg dose. There was no difference in mood swings between nilotinib and placebo at the 150 mg dose. Study author Charbel Moussa, PhD said their findings “suggest that 150 mg nilotinib is the optimal dosage to investigate in future Alzheimer studies.”

Nilotinib carries an FDA “black box warning” because it can cause cardiovascular issues that may lead to sudden death in cancer patients. No such incidents occurred at the lower doses tested in this trial. However, because the overall risk is rare (sudden death was reported in 0.3% of the 5,661 patients treated in nilotinib leukemia studies), the small sample size of this study cannot rule out a similar risk in Alzheimer’s patients.

The study lead author, R. Scott Turner, PhD, MD said future Alzheimer’s studies are now in the planning stage.