#AANAM – Tasigna Shows Sustained Safety in Phase 2 Trial, Larger Study Favored

Editor’s note: The Parkinson’s News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read the latest stories from the conference.

Tasigna (nilotinib), an approved leukemia medication, was seen to be safe and tolerable at high and low dose in people with Parkinson’s disease enrolled for more than two years in a Phase 2 trial, with no apparent treatment-related adverse side effects.

Greater benefits were also seen in disease symptoms and life quality among patients given this oral treatment at the higher 300 mg dose, and researchers recommended that dose be tested in a larger trial of treatment efficacy.

These findings were presented in the poster “Long-Term Safety and Clinical Effects of Nilotininb in Parkinson’s Disease,” at the 2021 American Academy of Neurology virtual meeting running through April 22.

The Georgetown University-sponsored trial (NCT02954978) enrolled 63 adults diagnosed with Parkinson’s, ages 40 to 90. Participants were randomized to once daily Tasigna capsules at either 150 mg or 300 mg, or to a placebo, for 12 months, followed by a 15-month open-label extension that further compared these two doses.

Trial findings, reported in 2019, showed the medication to be safe, and to increase dopamine levels in the brains of treated patients.

Newer extension trial data found that a worsening in motor and non-motor aspects of daily living — as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) I-II — stopped in people given Tasigna at 300 mg after about 15 months of treatment, and these scores remained stable or improved somewhat through to 27 months and study end. In contrast, these scores continued to worsen in patients on the lower, 150 mg dose.

Investigators did not observe a statistically significant difference in UPDRS-III scores — assessing motor symptoms — between these dose groups during “on” periods with levodopa. There also was no significant difference in total UPDRS I-III scores.

An analysis of dose groups within the total patient pool showed that a later start with Tasigna at lower dose did not prevent a significant worsening of combined UPDRS II and III scores, or in the total UPDRS I-III score, as compared with a later start at the 300 mg dose. [The research team did not define “late start” in its abstract. But as scores here extended for 27 months, this may be a reference to the trial’s placebo group, which only began treatment in the extension phase.]

Compared with Tasigna 300 mg, the 150 mg dose was associated with a significant decline in quality of life, as measured by the Parkinson’s Disease Questionnaire (PDQ-39). The investigators observed no change in cognitive measures between groups, as assessed using the Montreal Cognitive Assessment test.

Although no adverse side effects were reported as being related to Tasigna itself, two people in the high-dose group and two in the low-dose group withdrew from the trial due to severe adverse effects. One person in the high-dose group and two in the low-dose group withdrew voluntarily, for unreported reasons.

“This study provides evidence that nilotinib is safe and tolerated in Parkinson’s disease,” the researchers wrote.

Tasigna was designed to treat chronic myeloid leukemia, a cancer of the blood, as it blocks the activity of the BCR-ABL protein, which supports that cancer’s development. But in the brain, BCR-ABL also participates in Parkinson’s-related cellular events, including alpha-synuclein-induced nerve cell death and oxidative stress (damage to cells caused by high levels of so-called “free radicals”).

As such, it may work to eliminate toxic proteins that build in the brains of Parkinson’s patients.

Data from this trial could help to inform a larger study evaluating the efficacy of Tasigna at 300 mg in treating Parkinson’s, the researchers concluded.