Nilotinib Has Safe and Tolerable Profile in Alzheimer Disease


Results presented virtually at AAIC 2020 support a larger, multi-center, phase 3 study to determine the safety and efficacy of nilotinib in patients with Alzheimer disease.

Raymond S. Turner, MD, PhD

Raymond S. Turner, MD, PhD

Data from a phase 2 randomized, double-blind, placebo-controlled study (NCT02947893) of individuals with mild-to-moderate dementia due to Alzheimer disease (AD) revealed that treatment with nilotinib (Novartis) is safe, well-tolerated, and achieved pharmacologically relevant brain concentrations.1

The study, presented virtually by lead author Raymond Scott Turner, MD, PhD, director, Memory Disorders Program, and professor of neurology, Georgetown University Medical Center, at the Alzheimer’s Association International Conference (AAIC) 2020 annual meeting included 37 individuals, 27 of which were women (73%), with a mean age of 70.7 (standard deviation [SD], 6.48) years.

The results of the study showed that treatment with nilotinib was safe and well-tolerated, although more adverse events (AEs), particularly mood swings, were noted at the 300-mg dose (70.6%) compared with placebo (0%; P <.01).

Patients within the study were randomized 1:1 to nilotinib 150 mg once orally or matching placebo for 26 weeks followed by nilotinib 300 mg compared to matching placebo for another 26 weeks. Following the 52 weeks, amyloid burden was reduced in the temporal (—0.08; 90% CI, –0.21 to –0.01; P = .04) and frontal lobes (—0.19; 90% CI, 135–1018; P = .02) in the nilotinib group compared with the placebo group.

In addition to amyloid burden reduction, the treatment reduced cerebrospinal fluid (CSF) AB40 at 6 months (556 ng/ml; 90% CI, 135—1018; P = .02) and AB42 at 12 months (73.9 ng/ml; 90% CI, 14.3—137.9; P = .02) in the nilotinib group compared to the placebo. Furthermore, hippocampal volume loss was attenuated by —27% at 12 months and phospho-tau181 was reduced at 6 months (–31.6%) and 12 months (–39.6%) in the nilotinib group.

Turner and colleagues aimed to assess safety, tolerability, and pharmacokinetics of nilotinib, while measuring biomarkers in patients with mild to moderate dementia due to AD. Originally, 117 individuals approached to be enrolled in the study, but 13 were declined and 51 were excluded, leaving 37 to be randomized 1:1 to placebo or nilotinib groups.

Patients included in the study were ≥50 years of age, had biomarker confirmed AD with CSF level of AB42 <600 ng/ml and had Mini-Mental State Exam (MMSE) scores between 17 and 24 at screening. Those with non-AD dementia, probable AD with Down syndrome, history of clinically significant stroke, or evidence of epilepsy, focal brain lesion or head injury with loss of consciousness were among reasons for exclusion.

Nilotinib is currently being explored in patients with Parkinson disease (PD) as well. Data released in December 2019 demonstrated an alteration of exploratory biomarkers, as well as reasonable safety in patients with PD who were treated with nilotinib.2

In that study, those administered 150-mg nilotinib showed an increase in CSF levels of the dopamine metabolites homovanillic acid (159.80 nM; 90% CI, 7.04—312.60 nM; P = .04) and 3,4-dihydroxyphenylacetic acid (4.87 nM; 90% CI, 1.51—8.23 nM; P = .01), compared to the 300-mg nilotinib group which experienced a raise in 3,4-dihydroxyphenylacetic acid (7.52 nM; 90% CI, 2.35—12.69 nM; P = .01). Only those in the 300-mg group showed a reduction of α-synuclein oligomers (−0.04 pg/mL; 90% CI, −0.08 to 0.01 pg/mL; P = .03).

The FDA previously approved nilotinib under the brand name Tasinga for adult and pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia,3 however, several studies have found that the drug degrades alpha-synuclein and tau in animal models of neurodegeneration, and may increase dopamine metabolism, potentially treating motor and nonmotor symptoms.


1. Turner RS, Lawler A, Yusef N, et al. Nilotinib effects on safety, tolerability, and biomarkers in Alzheimer’s disease: a phase 2, double-blind, randomized, placebo-controlled study. Presented virtually at AAIC 2020. Poster 44628.

2. Pagan FL, Hebron ML, WIlmarth B, et al. Nilotinib effects on safety, tolerability, and potential biomarkers in parkinson disease. JAMA Neurol. Published online December 16, 2019. doi: 10.1001/jamaneurol.2019.4200

3. FDA approves nilotinib for pediatric patients with newly diagnosed or resistant/intolerant Ph+ CML in chronic phase [news release]. Silver Spring, MD: FDA; Published March 3, 2019. Accessed July 28, 2020.

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