Pipeline

CVXL – 0107

A new glutamate release inhibitor with demonstrated potential to improve the Quality of Life for Parkinson’s disease patients.

CVXL-0107 is a first in-class glutamate release inhibitor for the treatment of adult patients with Parkinson’s disease experiencing postural disturbances and/or dyskinesia. CVXL-0107 is currently in Phase IIa involving 30 patients. The product had previously demonstrated clinical efficacy for parkinsonian motor symptoms and dyskinesia treatment.

Glutamate is the major excitatory neurotransmitter in the basal ganglia, the brain structure involved in movement control. Through three distinct action sites, inhibition of glutamate release is expected to improve the life of Parkinson’s patients by:
– Reducing cortical input into the striatum, widely thought to be a cause of dyskinesia¹
– Improving motor symptoms, by decreasing globus pallidus-mediated movement inhibition²
– Slowing down neurodegeneration inhibiting glutamate-mediated excitotoxicity on the substantia nigra³

0107

CVXL-0107 is expected to demonstrate clinical efficacy ongoing Phase IIa study.

1. Huot, P., Johnston, T. H., Koprich, J. B., Fox, S. H. & Brotchie, J. M. The pharmacology of L-DOPA-induced dyskinesia in Parkinson’s disease. Pharmacol. Rev. 65, 171–222 (2013).
2. Wichmann, T. & DeLong, M. R. Functional and pathophysiological models of the basal ganglia. Curr. Opin. Neurobiol. 6, 751–8 (1996).
3. AlDakheel, A., Kalia, L. V & Lang, A. E. Pathogenesis-targeted, disease-modifying therapies in Parkinson disease. Neurotherapeutics 11, 6–23 (2014).
4. Jankovic, J. & Poewe, W. Therapies in Parkinson’s disease. Curr. Opin. Neurol. 25, 433–47 (2012).
5. http://www.pdf.org/en/parkinson_statistics

PARKINSON’S DISEASE

 

Parkinson’s disease (PD) is a major chronic and progressive neurodegenerative disorder, affecting 1-2% of individuals aged Under 65 years and 3% aged over 65 years worldwide.

PD results from the neurodegeneration of dopaminergic neurons in the substantia nigra leading to a decrease in the dopaminergic tone essential to movement.

First clinical signs are motor symptoms such as bradykinesia, rigidity, and resting tremor. As the disease progresses, motor coordination is dramatically reduced and non-motor symptoms appear (autonomic dysfunction, cognitive impairment, dementia).

Current medications involve symptomatic dopaminergic therapies, notably L-Dopa. However, the extended use of L-Dopa can lead to debilitating side effects such as dyskinesia, abnormal involuntary movement, experienced by 50 to 90% of PD patients when the disease progresses.

Current management of dyskinesia relies on adjusting L-Dopa dosing and/or adding a dopamine receptor to spare L-Dopa. Amantadine is the only prescribed anti-dyskinetic drug despite key constraints (limited in duration and has a poor safety profile).

A survey of KOLs highlighted that dyskinesia is the most important unmet medical need in the treatment of PD after a disease modifying agent.).