Phase 2 Data of Dipraglurant for Parkinson’s-associated, Levodopa-induced Dyskinesia Announced by Addex

Addex Therapeutics recently published the results of the company’s Phase 2 trial of its drug candidate dipraglurant in patients with levodopa-induced dyskinesia associated with Parkinson’s disease (PD-LID). The manuscript, “A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson’s Disease,” was published in the journal Movement Disorders.

Levodopa-induced dyskinesia, a form of dyskinesia associated with the drug levodopa used to treat PD, often involves hyperkinetic movements, including chorea, dystonia, and athetosis.

Dipraglurant is a novel oral small molecule that inhibits the metabotropic glutamate receptor 5 (mGluR5), and has the potential to be used in combination with levodopa or dopamine agonists for treatment of PD. Dipraglurant has a pharmacokinetic profile that mimics the profile of levodopa, making it a potential treatment for LID.

“The Phase 2 study suggests that dipraglurant improved dyskinesia in Parkinson’s disease patients,” said Sonia Poli, chief scientific officer of Addex. “We believe dipraglurant has a unique profile that is particularly suited for the treatment of PD-LID and we look forward to rapidly advancing dipraglurant into Phase 3 development.”

“Levodopa-induced dyskinesia can be debilitating in its own right and can impact the use of medications to treat Parkinson’s motor symptoms,” said Jamie Eberling, PhD, Michael J. Fox Foundation director of research programs, in a press release. “A therapy, such as dipraglurant, to control this side effect would have a great impact on the lives of many living with this disease.”

The article reports the data of the ADX48621-201 (NCT01336088) trial, a multicenter dose-escalation, double-blind, randomized, placebo-controlled, Phase 2A study in which 76 patients with Parkinson’s and moderate to severe levodopa-induced dyskinesia were randomly assigned to be treated with dipraglurant (from 50 mg once daily to 100 mg three times daily, 52 patients) or a placebo (24 patients).

The trial assessed the safety and tolerability of dipraglurant in patients with Parkinson’s as its primary endpoint. The secondary endpoints included the examination of the efficacy of drug compared with placebo in reducing levodopa induced dyskinesia in Parkinson’s patients and Parkinson’s symptoms. Other secondary endpoints included the assessment of the evaluation of the effect of co-administration of dipraglurant on L-dopa efficacy.

Results from the trial revealed no major safety issues with the treatment. Two patients did not complete the trial due to serious adverse events (SAE). The most commonly observed adverse events related to the treatment included nausea, fatigue, dyskinesia, and dizziness.

Dipraglurant was found to reduce the peak dose dyskinesia (as measured by the modified Abnormal Involuntary Movement Scale) on day 1 (50 mg) and on day 14 (100 mg) and across a three-hour post-dose period on day 14. The results also showed that treatment with dipraglurant did not worsen Parkinson’s symptoms.

According to the authors, treatment with dipraglurant was found to the safe and well-tolerated by patients with Parkinson’s in its first administration. However, the proven efficacy in overturning levodopa-induced dyskinesia needs to be confirmed in a larger group of patients, the researchers added.