Projects

V1512 – Treatment of Parkinson’s Disease

Under development by biopharmaceutical company, Vernalis, V1512 is a new, patented formulation of levodopa (L-dopa), the

Drug (brand/generic)

V1521

Company/licensee

Vernalis

Therapy class

Levodopa

Product description

Dopamine precursor

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Under development by biopharmaceutical company, Vernalis, V1512 is a new, patented formulation of levodopa (L-dopa), the mainstay of treatment of Parkinson’s disease (PD). The company obtained V1512 following its acquisition of Cita NeuroPharmaceuticals at the end of 2005.

Currently in phase III development, V1512 is designed to address some of the drawbacks inherent in older L-dopa preparations, which can 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.

IMPROVED DELIVERY OF L-DOPA WITH V1521

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 tremor, stiff limbs and slow movement, along with impaired balance and co-ordination. Current treatments aim to address the deficiency in dopamine production.

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 is an effervescent formulation of the more soluble form of L-dopa, levodopa methylester, in combination with the decarboxylase inhibitor, carbidopa. Decarboxylase inhibitors enhance absorption of L-dopa and help prevent peripheral side effects that can occur from the rapid systemic decarboxylation of L-dopa to dopamine. Vernalis hope that V1512 will be absorbed more rapidly and consistently than conventional L-dopa preparations and thus offer patients the potential of greater drug efficacy.

CLINICAL TRIALS SUGGEST V1521 HAS A RAPID ONSET OF ACTION

The clinical efficacy and safety of V1512 has 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 regulatory approval in Italy, where Chiesi already market the drug as rescue (fast-onset) treatment for PD. Vernalis has worldwide rights to V1512, with Italy the only exception.

V1512 is now entering phase III development; in which the reduction in total daily ‘off’ episodes will be used as primary endpoint in the pivotal trials. Pharmacokinetic studies comparing plasma levels of V1512 with Sinemet, a conventional and widely used L-dopa preparation, are also ongoing.

BUILDING A PORTFOLIO OF DRUGS FOR PD

While L-dopa remains an important symptomatic treatment for PD, over time patients on L-dopa therapy tend to develop dyskinesias (involuntary movements) and ‘on-off’ motor syndromes. New therapies are still needed to slow disease progression, improve symptoms in early disease, and improve ‘off’ time without worsening dyskinesia in later-stage disease.

In addition to V1512, Vernalis is developing a selective adenosine A2A receptor
antagonist, V2006, for the treatment of PD. As their name implies, this new class of antiparkinsonian drugs target adenosine A2A receptors, which are expressed selectively in the basal ganglia. Adenosine is a neurotransmitter involved
in motor co-ordination and movement control.

Evidence from preclinical studies suggest that adenosine A2A receptor antagonists can reverse motor deficits in models of PD without causing dyskinesia and other dopaminergic-related side effects. Potentially, this new class of
non-dopaminergic agents may help to restore motor function in PD patients without inducing the adverse effects that limit the clinical utility of today’s PD drugs.

MARKETING COMMENTARY

Estimated to affect over 4 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.

In the short- to medium term, new formulations of L-dopa, such as Vernalis’ V1521, have potential to improve symptomatic treatment options. Longer-term, the market is likely to see the introduction of new drugs with different modes of action such as
dopamine re-uptake inhibitors and non-dopaminergic, adenosine receptor antagonists.

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