Foliglurax (PTX002331) originally was developed by Prexton Therapeutics, which then was acquired by Lundbeck, as an investigative treatment for Parkinson’s disease. In March 2020 the company terminated the development program of foligurax because it failed to show sufficient efficacy in a Phase 2 clinical trial called AMBLED (NCT03162874).

How does foliglurax work?

Parkinson’s is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the part of the brain responsible for movement and coordination. Foliglurax activates a distinct system of nerve cells possessing specific glutamate receptors, called metabotropic glutamate receptor 4 (mGluR4), which compensate for the deficiency of dopamine. Like dopamine, glutamate is a signaling molecule that nerve cells release to send messages to other nerve cells.

Several studies in animal models suggested that activating mGluR4 could reduce the motor symptoms of Parkinson’s disease, such as resting tremor, muscle rigidity, and uncontrolled movements (called dyskinesia).

Foliglurax in clinical trials

A single and multiple ascending oral dose Phase 1 trial (NCT02639221) testing foliglurax in healthy volunteers was completed in 2016. The results showed that foliglurax was safe and well-tolerated. It also had an excellent pharmacokinetic profile (how the treatment moves in the body).

Prexton launched a Phase 2 clinical trial (NCT03162874) in 2017 to test foliglurax in Parkinson’s patients. The trial, called AMBLED, enrolled 157 participants in sites across six European countries (U.K., Germany, France, Austria, Spain, and Italy). The double-blind, randomized, placebo-controlled, parallel-arm study assessed the effectiveness, safety, and tolerability of foliglurax in reducing the motor complications of levodopa therapy in patients experiencing end-of-dose wearing-off and levodopa-induced dyskinesia (LID).

Two groups received oral doses of the treatment (10 mg and 30 mg) over 28 days. A third group received a placebo. The primary outcome measure was to assess changes in patients’ daily awake off episodes. This was based on patient diary entries between the start and end of the treatment. Secondary outcome measures included assessing changes in LID within the same period of time.

Lundbeck announced in March 2020 data from AMBLED showing that both doses of foliglurax failed to meet the study goals of demonstrating a significant positive effect in reducing levodopa’s “wearing-off” effect and LID compared to a placebo. Based on those results, Lundbeck decided to terminate foliglurax’s development program.

 

Last updated: April 8, 2020

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