NLX-112 trial results — behind the headlines

Designed to treat dyskinesia (distressing, uncontrollable movements that are a side effect of current drugs), the 8-week study has shown that NLX-112 may also improve motor symptoms.

Let’s take a closer look at NLX-112, the results that have been shared and the next steps for this promising treatment.

What is this new drug NLX-112 and where did it come from?

NLX-112 (also known as befiradol) was originally developed by a French company called Pierre Fabre and works by targeting brain cells that make and release serotonin.

Serotonin is a chemical that carries messages between nerve cells in the brain and throughout the body. It plays a role in a wide variety of things including mood, sleep, digestion and nausea to name just a few.

Pierre Fabre tested NLX-112 in patients with diabetic neuropathy (a kind of nerve damage caused by diabetes) in the late 1990s. The trial did not show sufficient evidence of benefit so the company decided to stop investigating it as a treatment.

But around this time, scientists were beginning to understand that brain cells that respond to serotonin may play an important role in regulating movement. So could NLX-112 have the potential for treating Parkinson’s?

Why might NLX-112 be helpful for Parkinson’s?

A company called Neurolixis decided to explore the potential of NLX-112 for Parkinson’s. They believed that the drug could have particular promise for treating dyskinesia: a side effect of Parkinson’s medications that causes unwanted and uncontrollable movement.

Dr Adrian Newman-Tancredi from Neurolixis explains:

"The main treatment for Parkinson’s currently is a drug called levodopa. This drug is taken up by dopamine-producing cells, which convert it into dopamine and then release it to enable the brain to send messages to control movement.

"That works well initially but as Parkinson’s progresses the dopamine-producing cells become more damaged and fewer in number. The levodopa dose can be increased to compensate but by this time the dopamine cells are struggling to handle all this levodopa.

"This leads to levodopa being taken up by neighbouring serotonin-producing brain cells. The serotonin cells start converting levodopa into dopamine and releasing it but they don’t control this properly which leads to surges in dopamine, essentially a dopamine overload, which are an important trigger for dyskinesia.

"That’s why we were excited about the potential of NLX-112, a drug that targets serotonin cells, to address this problem."

What happened in the recent clinical trial?

NLX-112 was tested in 22 participants with Parkinson’s with dyskinesia in an 8-week trial at several centres in Sweden. The trial was co-funded by Parkinson’s UK and The Michael J. Fox Foundation.

15 participants received NLX-112 and 7 participants received a dummy pill (or placebo). Participants either received NLX-112 or the placebo in increasing doses during the initial 4 weeks, to minimise the potential side effects. They stayed on the maximum dose for 2 weeks, and then were weaned off the drug over the final 2 weeks.

As this was the first time this drug had been given to people with Parkinson’s, the primary focus of the study was to assess the safety and tolerability of NLX-112 for people with the condition.

The results indicate that NLX-112 was well tolerated by patients. There were a similar number of side effects reported by those in the placebo group to those who received NLX-112.

The participants were also carefully assessed throughout the study to explore the effects of NLX-112 on motor symptoms and dyskinesia.

These assessments included a ‘levodopa challenge’ at 3 points within the study where patients received an extra dose of levodopa to induce dyskinesia. Other assessments included patient reported outcomes where participants were asked to rate their own symptoms and level of dyskinesia.

The results of these assessments showed that NLX-112 treatment:

• reduced dyskinesia in a manner similar to amantadine (the current frontline treatment for dyskinesia)
• improved motor symptoms in a manner similar to dopamine agonist medications.

Importantly, these improvements were seen with relatively low doses of NLX-112 and seemed to increase throughout the study, suggesting that the full benefit of the treatment may increase with higher doses and longer treatment.

Overall, the results are very promising as they suggest that NLX-112 is well tolerated and may have dual benefits for people with Parkinson’s.

What are the next steps for NLX-112?

The results reported at the World Parkinson Congress are very promising but it’s important to remember that this was an early-stage, small and short-term study, known as a Phase 2a, which was focused primarily on safety and understanding possible dosing levels of NLX-112.

This means that further studies are still required to prove the effectiveness of NLX-112.

These are likely to include first a Phase 2b study to further explore the optimum dose and look at the potential effectiveness of NLX-112 in a larger group over a longer period.

And then, if this is successful, a Phase 3 study in a large population of people with Parkinson’s will also be needed to provide sufficient evidence on safety and effectiveness of the drug.

Neurolixis are already seeking investment to get the next phase of studies up and running as quickly as possible. If these next studies provide positive results NLX-112 could be available as a new treatment for Parkinson’s by 2030.

Learn more about the results of the study by watching the Hot Topics presentation on YouTube.