Addex Reports Positive Top Line Phase IIa Data for Dipraglurant in Parkinson's Disease Levodopa-Induced Dyskinesia (PD …

PLAN-LES-OUATES GENEVA, SWITZERLAND--(Marketwire -03/21/12)-

Addex Therapeutics / Addex Reports Positive Top Line Phase IIa Data for Dipraglurant in Parkinson's Disease Levodopa-Induced Dyskinesia (PD-LID)

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Geneva, Switzerland, 21 March 2012 - Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today positive top line data from a Phase IIa clinical study of dipraglurant in Parkinson's disease (PD) patients suffering from debilitating levodopa-induced dyskinesia (LID). The data show that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated statistically significant reduction in LID severity with both 50mg and 100mg doses. Dipraglurant appears to reduce dystonia severity in addition to chorea, the two major LID components. A full analysis of the data will be presented at a scientific forum in 2012.

Dipraglurant is an oral, small molecule allosteric modulator that inhibits selectively the metabotropic glutamate receptor 5 (mGluR5), a Class C G- Protein Coupled Receptor (GPCR), with potential to be used in combination with levodopa or dopamine agonists or as a standalone treatment for PD-LID, PD-related motor symptoms, non-motor symptoms of PD and other movement disorders.

The Coordinating Investigator of the dipraglurant study, Olivier Rascol, MD, PhD, Professor of Clinical Pharmacology at the Toulouse University Hospital, and one of the world's leading experts on treating Parkinson's disease commented: "There is no drug approved for the treatment of PD-LID and dipraglurant is an exciting new approach. The study was successful in achieving the primary objective of good safety and tolerability. In addition, these proof of concept data are promising and warrant further investigation of dipraglurant in Parkinson's disease."

In this double-blind, placebo-controlled study conducted in the US and Europe, the primary objective was to demonstrate safety and tolerability in PD-LID patients. In addition, the trial was designed to evaluate exploratory efficacy as a secondary objective. Efficacy was measured using the modified Abnormal Involuntary Movement Scale (mAIMS), patient diaries documenting "off-time" (impaired voluntary movement), "on-time" (with or without dyskinesia) and sleep. Additional endpoints include the Unified Parkinson's Disease Rating Scale (UPDRS), the Clinician & Patient Global Impression of Change (CGIC & PGIC), and an evaluation of the patients' mood using the Hospital Anxiety & Depression Score. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.

"Dyskinesia is a top priority for our Foundation because of its significant negative impact on patients' quality of life," said Todd Sherer, PhD, CEO of The Michael J. Fox Foundation. "A successful treatment for PD-LID will change the way Parkinson's disease is treated by enabling physicians to use levodopa earlier and more effectively. To this end, since 2006, we have been funding research on mGluR5 inhibition as one of the most promising potential treatments for LID. We are proud to have been involved in funding this trial of dipraglurant by Addex, which is at the forefront of this effort."

A total of 76 male and female patients (dipraglurant, n = 52; placebo, n = 24) with moderate or severe PD-LID were randomized into the study. Patients followed a dose-titration regimen, receiving 50mg doses from Day 1 to Day 14 and then 100mg from Day 14 until Day 28. This first-in-patients study met its primary objective of demonstrating safety and tolerability in patients with PD. There were no significant changes in any safety monitoring parameters and, in particular, no changes in liver function tests were seen in either treatment group. Both the 50mg and 100mg dose levels were well tolerated. The incidence of adverse events was similar in both active and placebo groups (88.5% for dipraglurant versus 75% for placebo). Typical mGluR5-type adverse events (vertigo, visual disturbance, feeling drunk) were seen in less than 10% of patients in the dipraglurant group but were not severe or dose limiting.

Exploratory efficacy data showed an anti-dyskinetic effect on observer evaluated mAIMS and in patient reported diary data. Both the 50mg and 100mg doses of dipraglurant showed a statistically significant reduction in LID. Peak mAIMS was significantly reduced on Day 1 (50mg; p = 0.042) and on Day 14 (100mg; p = 0.038). The targeted magnitude of effect of either a 30% reduction in mAIMS or a 20% separation from placebo was achieved on Days 1, 14 and 28. The magnitude of reduction in mAIMs was maintained for dipraglurant on Day 28 (100mg), but not statistically significant due to an increase in placebo response on that day. Similar results were seen for the area under the curve (AUC) mAIMS evaluation in the total 3 hour post levodopa dosing period, with about a 30% reduction in the dipraglurant group at Days 14 and 28, which was statistically significant at Day 14 (p = 0.042). In a subset of patients with levodopa-induced dystonia, dipraglurant appears to have reduced dystonia severity. The UPDRS Part III (motor scores) performed during mAIMS evaluation, indicated that dipraglurant did not interfere with levodopa efficacy.

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Addex Reports Positive Top Line Phase IIa Data for Dipraglurant in Parkinson's Disease Levodopa-Induced Dyskinesia (PD ...