Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, announced today that the US Food and Drug Administration (FDA) has granted orphan drug designation to dipraglurant for the treatment of levodopa-induced dyskinesia associated with Parkinson's disease (PD-LID). Orphan drug status provides Addex with a number of benefits including reduced development costs and seven years US market exclusivity from launch. Dipraglurant is a novel small molecule inhibitor of the metabotropic glutamate receptor 5 (mGluR5) that has successfully completed Phase II proof-of-concept testing in Parkinson's disease (PD) patients suffering from debilitating levodopa-induced dyskinesia (LID), an indication that has no approved treatment options. Addex is currently conducting an mGlu5 receptor occupancy clinical trial and is preparing to start a Phase III pivotal trial in PD-LID.
"Orphan drug status for dipraglurant in PD-LID is an important regulatory milestone for us and recognizes the therapeutic benefits that dipraglurant can bring to PD patients", said Sonia Poli, CSO of Addex. "Dipraglurant has already demonstrated its potential to reduce dyskinesia in PD patients and we have started consultation with the FDA to define the clinical development program in this rare disease."
"Achieving orphan drug designation is a key milestone as we execute our strategy of focusing Addex portfolio of clinical programs in rare neurological disorders", said Tim Dyer, CEO of Addex. "We recently reported positive interim data from our ongoing mGluR5 receptor occupancy clinical trial and now plan to move dipraglurant directly into a Phase III pivotal trial in the US."
About Orphan Drug Designation
Orphan drug designation is granted by the FDA Office of Orphan Products Development (OOPD) to novel drugs that treat a rare disease or condition affecting fewer than 200,000 patients in the United States. The designation provides the sponsor with a seven-year period of U.S. marketing exclusivity from launch, as well as tax credits for clinical research costs, the ability to apply for annual grant funding, clinical research trial design assistance, and waiver of Prescription Drug User Fee Act (PDUFA) filing fees.
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 Levodopa-Induced Dyskinesia Associated with Parkinson's Disease
PD-LID are involuntary movements that appear after 3-5 years of treatment with dopamine replacement therapies. They may affect any body area e.g. face, trunk, limbs, that occur when a patient takes levodopa. Patients suffering from LID commonly present with irregular migrating contractions or twisting and writhing due to dystonia, chorea, however other forms of abnormal movements have also been observed; peak-dose dyskinesia is the most common form and is associated with peak plasma levels of levodopa. Symptoms of LID are serious and can restrict the dosing of levodopa which may result in inadequate control of Parkinsonian symptoms. In addition to the impact on quality of life associated with uncontrollable involuntary movements, patients with LID are easily fatigued, present a risk of injury to themselves as well as caretakers, and suffer pain due to dystonia.