Addex Dipraglurant Positive Phase 2 Data in PD-LID Published in Leading Peer Reviewed Journal of the Movement Disorder Society
Geneva, Switzerland, 2 June 2016 – Addex Therapeutics (SIX: ADXN) announced today that results from its Phase 2 clinical study of dipraglurant in levodopa-induced dyskinesia associated with Parkinson’s disease have been published in the online issue of the peer-reviewed journal Movement Disorders, “A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease” Mov Disord. 2016 May 23.
Dipraglurant is being developed by Addex for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease. Dipraglurant is a novel, highly potent mGluR5 negative allosteric modulator (NAM) with a pharmacokinetic profile that mimics that of levodopa, making it particularly well suited to treat LID.
“The Phase 2 study suggests that dipraglurant improved dyskinesia in Parkinson's disease patients.” commented 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 III 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, MJFF Director of Research Programs. "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 publication reports the results of clinical trial ADX48621-201 (NCT01336088). The study was a phase 2A double-blind, placebo-controlled, randomized (2:1), 4-week, parallel-group, multicenter dose-escalation (from 50 mg once daily to 100 mg 3 times daily) clinical trial involving 76 PD subjects with moderate to severe levodopa-induced dyskinesia. Fifty-two patients were exposed to dipraglurant and 24 to placebo.
The primary objective of the study was to evaluate the safety and tolerability of ADX48621 in Parkinson's disease patients following four weeks of dosing. The secondary objectives of the study included the evaluation of the efficacy of ADX48621 compared with placebo in reducing levodopa induced dyskinesia in patients with Parkinson's; the evaluation of the effect of ADX48621 on symptoms of Parkinson's disease and patient ability to function, and the evaluation of the effect of co-administration of ADX48621 on L-dopa efficacy. The study was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.
The results show that there were no major safety concerns in the trial. Two subjects did not complete the study because of adverse events. Most frequent adverse events included dyskinesia, dizziness, nausea, and fatigue. Dipraglurant significantly reduced peak dose dyskinesia (modified Abnormal Involuntary Movement Scale) on day 1 (50 mg, 20%; P = 0.04) and on day 14 (100 mg, 32%; P =0 .04) and across a 3-hour post-dose period on day 14 (P = 0.04). Most importantly, there was no evidence of worsening of parkinsonism.
The authors conclude that dipraglurant proved to be safe and well tolerated in its first administration to PD patients and that its efficacy in reversing levodopa-induced dyskinesia warrants further investigations in a larger number of patients.
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 Parkinson's disease levodopa-induced dyskinesia (PD-LID), motor and non-motor symptoms of Parkinson's disease and other movement disorders. In a double-blind, placebo-controlled, US and European Phase II study in PD-LID, data showed that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated a statistically significant reduction in LID severity with both 50 and 100 mg doses. Dipraglurant reduced dystonia severity in addition to chorea, the two major LID components. Efficacy was measured using the modified Abnormal Involuntary Movement Scale and 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, the Clinical and Patient Global Impression of Changes scales, and an evaluation of the patient’s mood using the Hospital Anxiety and Depression Scale. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.
About The Michael J. Fox Foundation for Parkinson’s Research
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $525 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for neurological disorders. Addex lead drug candidate, dipraglurant (mGluR5 negative allosteric modulator or NAM) has successfully completed a phase IIa POC in Parkinson’s disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter phase III for PD-LID with support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). In parallel, dipraglurant’s therapeutic use in dystonia is being investigated with support from the Dystonia Medical Research Foundation (DMRF). Addex second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc for epilepsy. In addition, ADX71441 (GABAB receptor PAM) has received regulatory approval to start phase I and is being investigated for its therapeutic use in Charcot-Marie-Tooth Type 1A disease (CMT1A), alcohol use disorder and nicotine dependence. Discovery programs include mGluR4PAM for neurodegenerative diseases, mGluR7NAM for psychosomatic disorders and TrkBPAM for neurodegenerative disorders and mGluR3PAM which is being advanced in collaboration with Pierre Fabre Pharmaceuticals. Allosteric modulators are an emerging class of small molecule drugs which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. Addex allosteric modulator drug discovery platform targets receptors and other proteins that are recognized as essential for therapeutic intervention – the Addex pipeline was generated from this pioneering allosteric modulator drug discovery platform.
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