V1512 is a combination of carbidopa and melevodopa indicated for treating Parkinson’s disease (PD). The drug is developed by Chiesi Farmaceutici, an Italian pharmaceutical company, and Vernalis, a biotech company based in the UK.
Chiesi markets the drug in Italy under the brand name Sirio®, while Vernalis holds the worldwide rights to V1512, excluding Italy. Vernalis obtained V1512 following the acquisition of Cita NeuroPharmaceuticals, a small molecule drug candidates developer, at the end of 2005.
V1512 is a new, patented formulation of levodopa (L-dopa), the mainstay of the treatment of PD. It is designed to address some of the drawbacks inherent in older L-dopa preparations, which greatly reduce its efficacy.
If approved, V1512 will join Vernalis’ Apokyn (apomorphine). The latter is already marketed in the USA for the acute, intermittent treatment of immobilising ‘off’ episodes in patients with advanced PD.
Parkinson’s disease causes and symptoms
PD is a disease of the basal ganglia arising from the loss of dopamine-producing cells in the substantia nigra. The loss of dopamine, a major neurotransmitter, produces the characteristic motor symptoms of PD that include tremors, stiff limbs and slow movement, along with impaired balance and coordination. Current treatments aim to address the deficiency in dopamine production.
Estimated to affect over four million people worldwide, PD is the second most common neurodegenerative disease after Alzheimer’s disease. Primarily a disease of the elderly, its prevalence is projected to rise as the proportion of elderly people in the Western population continues to increase.
The prevalence of the disease has doubled in the last two and a half decades, affecting more than 8.5 million people worldwide, as of 2019.
L-dopa, a precursor of dopamine, has been used as a treatment for PD for over 30 years and remains the gold standard of treatment. However, current formulations of L-dopa are often poorly absorbed following oral administration. This can lead to an increased frequency of ‘off’ episodes when patients experience partial or total loss of mobility.
V1512’s mechanism of action
V1512 is an effervescent formulation of the more soluble form of L-dopa, melevodopa (levodopa methyl ester), in combination with the decarboxylase inhibitor, carbidopa. Decarboxylase inhibitors enhance the absorption of L-dopa and help prevent peripheral side effects that can occur from the rapid systemic decarboxylation of L-dopa to dopamine.
V1512 can be absorbed more rapidly and consistently than conventional L-dopa preparations and thus offer patients the potential for greater drug efficacy.
Clinical trials on V1521
The clinical efficacy and safety of V1512 have been established in a series of studies, which have shown evidence of a significantly more rapid onset of action and of reduced ‘off’ episodes (improved mobility). The trials have also demonstrated a more reliable drug response in comparison with conventional L-dopa preparations. These studies formed the basis of its regulatory approval as rescue (fast onset) treatment for PD in Italy.
V1512 completed the phase III clinical trial in which the reduction in total daily ‘off’ episodes was used as the primary endpoint. Pharmacokinetic studies comparing plasma levels of V1512 with Sinemet, a conventional and widely used L-dopa preparation, were also conducted.
V1512 was found to have a more reliable L-dopa pharmacokinetic profile compared to standard-release L-dopa/carbidopa, with more effective L-dopa delivery in the early morning and afternoon. Its pharmacokinetic parameters varied less compared to L-dopa/carbidopa, both over time and between patients.
The results demonstrated that the administration of V1512 causes lesser fluctuation in L-dopa exposure in patients with PD.