allosteric modulators for human health


Dipraglurant-IR for Parkinson's disease levodopa-induced dyskinesia

Dipraglurant is a novel oral small molecule, which inhibits the metabotropic glutamate receptor 5 (mGluR5), and has potential to be used in combination with levodopa or dopamine agonists for treatment of Parkinson’s disease (PD). Our initial focus is on testing dipraglurant for the treatment of PD levodopa-induced dyskinesia (PD-LID). Together with a partner, we hope to study dipraglurant’s potential for treatment of the non-motor symptoms of PD (e.g. anxiety, depression and impulse control disorders), motor symptoms of PD and also non-parkinsonian dystonias.

During the neurodegenerative process of PD, loss of striatal dopaminergic neurons results in an increase in gluatamatergic output from the substantia nigra. mGluR5 are abundant in the striatum and implicated in the excess glutamate activity observed in PD. Blockade of mGluR5 has been shown to have anti-PD and antidyskinetic effects in a variety of animal models as well as early trials in patients.

We believe a successful treatment for PD-LID will change the way Parkinson’s disease is treated, by enabling physicians to use the most effective drug for Parkinson’s disease – levodopa – earlier and more aggressively. In addition, based on robust preclinical data, potential label expansions for dipraglurant include: PD motor symptoms and/or non-motor symptoms, like co-morbid anxiety and depression, as well as non-parkinsonian dystonias.

We recently reported data from a double-blind, placebo-controlled, EU and U.S. trial of dipraglurant in 72 PD-LID patients, the primary objective being safety and tolerability. In addition, the trial was designed to evaluate exploratory efficacy as a secondary objective. Efficacy is being measured using: the modified Abnormal Involuntary Movement Scale; patient diaries documenting on time (with/without dyskinesias), off time and sleep time; the Unified Parkinson’s Disease Rating Scale; the Clinician & Patient Global Impression of Change; and finally, an evaluation of the patients’ mood, using the Hospital Anxiety & Depression Score.

Full data from the study, which is partially funded by a grant from The Michael J Fox Foundation for Parkinson’s Research, will be presented at a conference later this year. The Michael J. Fox Foundation Blog posted a commentary on our Phase IIa top line data.

While dipraglurant has broad potential for treating Parkinson’s and other diseases, the most direct path to market is treatment of PD-LID. No drug is approved for PD-LID and LID has been identified by the regulatory authorities, patient advocacy groups such as Michael J. Fox Foundation and key opinion leaders as a very important unmet medical need. The potential market opportunity for dipraglurant in Parkinson’s disease is well in excess of $1 billion, according to market research carried out by Datamonitor for Addex. Further label expansion outside of Parkinson’s disease, for example to treat non-parkinsonian dystonias, could more than double the peak sales potential for dipraglurant.

As a result, we think that dipraglurant is a compelling partnering opportunity. We are seeking a partner with the vision, expertise and capability to fully exploit dipraglurant’s attractive commercial potential.  With the Phase IIa data for dipraglurant-IR in hand, we now plan to engage in partnership discussions with a view towards having a partner on board before the end of 2012.