Nilotinib: results from the latest trial

Back in 2017, US researchers announced the launch of a phase 2 clinical trial of the cancer drug nilotinib in people with Parkinson’s. Now the top-line results of the study are out.

Dr Beckie Port
Dec 6, 2019 · 6 min read
Photo by Hal Gatewood on Unsplash

Brief summary

  • Nilotinib is a cancer drug that in lab-based studies protects dopamine-producing brain cells and reduces alpha-synuclein build-up
  • In the latest phase 2 trial, nilotinib was found to be safe and tolerable but was not seen to have significant beneficial effects, although there were hints of some positive effects in the full results
  • Studies of other repurposed and experimental drugs that work in a similar way to nilotinib continue.

What is nilotinib and why is it being tested in Parkinson’s?

Nilotinib is a drug that is already approved for treating leukaemia. Researchers have been interested in its potential to treat Parkinson’s as it reduces the activity of c-Abl, a protein linked to a number of cellular pathways that are affected in Parkinson’s.

In the lab, molecules that target c-Abl in this way (c-Abl inhibitors) have been seen to reduce the accumulation of toxic alpha-synuclein, protect the brain cells affected by Parkinson’s and improve motor symptoms in animal models of the condition.

In 2015, the results of a phase I study of nilotinib made media headlines. The study found that people with Parkinson’s who took low doses of the repurposed drug over a period of 24 weeks saw improvements in thinking, movement and non-motor symptoms. These are published in the Journal of Parkinson’s Disease.

However, the small size of the study, involving only 12 patients, and the lack of a placebo group left many questions unanswered. It was time for a larger trial.

NILO-PD: a phase 2 clinical trial of nilotinib

Based on positive results from the phase 1 study, NILO-PD was launched to further investigate the drug’s safety and its potential for treating Parkinson’s symptoms.

This 12-month trial, coordinated through the Clinical Trial Coordination Center at the University of Rochester, recruited 75 people with moderate to advanced Parkinson’s. It was carried out at 25 sites through the Parkinson Study Group, the largest not-for-profit scientific network of Parkinson’s disease centres in North America.

Participants were randomly assigned to receive nilotinib (150mg or 300mg doses of daily over 12 months) or the placebo and neither researchers nor participants knew which treatment they are getting. This type of trial design is known as a randomised, double-blind, placebo-controlled trial and is the gold standard for clinical trials as it helps to counter the placebo effect.

The research team aimed to evaluate the safety of low doses of the drug and monitor its effect on Parkinson’s symptoms and biomarkers in cerebrospinal fluid — the colourless fluid that surrounds the brain and spinal cord.

Top-line results from the trial

Results have now been shared after the participants receiving the active treatment and placebo were unblinded on the 15 November. This was the first time that the effects of the drug could be assessed.

Unfortunately, while nilotinib was seen to be safe and tolerable in the participant group, top-line results show it doesn’t appear to have a clinically meaningful benefit or biological effect that might benefit those with Parkinson’s.

These top-line results, originally planned for 2020, have been announced early in an effort to keep the Parkinson’s community informed of new scientific findings as quickly as possible — a key commitment of the NILO-PD Steering Committee made up of both researchers and those affected by Parkinson’s. More detail will likely come with the full results of the study.

In the release from Northwestern University, Committee member Gary Rafaloff, who was diagnosed with Parkinson’s in 2012, has been quoted:

"No one wanted this trial to succeed more than I did...

“If I had qualified, I would have participated as a volunteer. Instead, I spent over two years working with the other committee members to ensure that the trial was designed and administered with the utmost rigor. Nevertheless, the results are what they are. The good news is that there are several other upcoming trials that we can focus on as we look forward to future success."

Full results published

A little over a week after the top-line results were published, a glimmer of hope could be seen in the full results.

The principal investigator of the study Fernando Pagan, MD, Georgetown neurology professor and medical director of the GUMC Translational Neurotherapeutics Program was quoted saying:

“We see that subjects on nilotinib performed better overall on motor testing and had a better quality-of-life measurement during the study than the placebo group.”

And there were hints that nilotinib might reduce the levels of toxic proteins and may even boost natural dopamine release.

But the results are not clear cut. No significant differences were seen in motor and nonmotor outcomes between the nilotinib groups and the placebo group because the study was under power. As such the placebo effect cannot be ruled out.

Additionally, some benefits were seen only in those taking 150mg of nilotinib. For instance, those taking 150mg, but not 300mg, demonstrated a reduction of toxic alpha synuclein but this reduction was not statistically significant. However, there was a significant reduction in toxic tau protein in those taking both 150mg and 300mg of nilotinib compared to the placebo group.

So what’s next?

While more research is still needed to confirm any potential benefits of nilotinib, a number of other c-Abl inhibitors are currently progressing through drug development and clinical trials for Parkinson’s.

• Other chemotherapy drugs

The c-Abl inhibitors imatinib and bafetinib have been shown to reduce the loss of dopamine-producing brain cells in animal models of Parkinson’s. But questions remain on if these drugs would be able to cross the blood-brain-barrier — a protective barrier that keeps pathogens and certain drugs from reaching the brain.

So researchers have recently looked to radotinib, another repurposed cancer drug that has been reported to more effectively access the brain, better safety profiles and may also have a longer duration of effect than nilotinib and other c-Abl inhibitors. While radotinib has yet to reach clinical trials for Parkinson’s, studies in animal models have reported promising results.

• Experimental drug K0706 (also known as SCC-138)

Earlier in 2019, a phase 2 clinical trial of new experimental drug molecule K0706 was launched in the US.

This study comes after a successful phase 1 study, which finished in May 2019, and earlier lab-based studies which showed that K0706 reduced the loss of dopamine-producing neurons and improved behavioural symptoms in animal models of Parkinson’s.

Like the NILO-PD, the phase 2 PROSEEK study is also double-blind and placebo-controlled trial. It is currently looking to recruit 504 participants with early Parkinson’s in the US and Hungary. The study will evaluate the safety and effectiveness of two doses of K0706 against a placebo and assess changes in motor function using the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).

Only time will tell if these future trials show that c-Abl inhibitors may have the long term beneficial effect needed to treat Parkinson’s.

Interested in taking part?

There are currently no trials of c-Abl inhibitors recruiting in the UK but there are many other Parkinson’s research studies underway that do need participants — including clinical trials testing potential new therapies.

Find studies to suit you using our Take Part Hub.

Full results were published on the 16 December in the journal JAMA Neurology and highlight some positive findings. This blog has been updated to incorporate these results.

Parkinson’s UK

Get the latest research news, discover more about Parkinson’s and read about how others are getting involved. For information and support, visit

Dr Beckie Port

Written by

Research Communications Manager at @ParkinsonsUK. Ex-researcher in oncology and virology.

Parkinson’s UK

Get the latest research news, discover more about Parkinson’s and read about how others are getting involved. For information and support, visit

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