In a deal that could potentially be worth up to US$820 million, GlaxoSmithKline (GSK) has gained the exclusive, worldwide development and commercialization rights to retigabine, a first-in-class potassium-channel opener developed by Valeant Pharmaceuticals for the treatment of epilepsy. GSK will also gain the rights to Valeant's back-up compounds that target potassium channels.
Valeant receives an upfront payment of $125 million, and will share up to 50% of net profits on retigabine sales in markets including the US. Valeant could also receive up to $545 million based on the achievement of milestones and the development of additional indications for retigabine (which is also in Phase II trials for the treatment of post-herpetic neuralgia), and up to $150 million based on the achievement of milestones for back-up compounds, such as VRX698.
Many established anti-epileptic drugs (AEDs) target voltage-gated sodium and calcium channels or potentiate the inhibitory effects of GABA (-aminobutyric acid) (Nature Rev. Neurosci. 5, 553–564; 2004). Retigabine, however, is thought to reduce the potential for epileptic seizures primarily by opening neuronal voltage-gated potassium channels, thereby decreasing cellular excitability (Epilepsy Res. 73, 1–52; 2007).
Two placebo-controlled Phase III trials of retigabine as adjunctive therapy for adult epilepsy patients with refractory partial-onset seizures have recently been completed, and it has been reported that the primary efficacy end points were met for all three doses tested (GSK press release; see Further information). Valeant and GSK are expected to file for approval in the US and in Europe by early 2009.
Multiple AEDs are currently available. Nevertheless, as Svein Johannessen, Senior Researcher, The National Center for Epilepsy, Norway, notes: "There is still a need for new AEDs as the clinical efficacy, tolerability, toxicity and pharmacokinetic properties of existing AEDs may not be satisfactory." Indeed, about one-third of patients with epilepsy are refractory to existing treatments.
"Retigabine's novel mode of action might represent an efficient way of reducing epileptogenic activity and ongoing underlying pathophysiological processes, and it has primarily renal elimination and low potential for drug interactions," adds Johannessen. "Comparative studies with other AEDs are needed to show how this drug fits in with those already available."
For GSK, success for retigabine might also help offset the anticipated loss of sales for their drug lamotrigine (Lamictal), a sodium-channel antagonist used for the treatment of epilepsy and bipolar disorder. Worldwide sales of lamotrigine were reported by GSK to be UK£1.1 billion in 2007 (GSK Annual Report 2007; see Further information), but it is now exposed to competition from generic versions in both Europe and the US.
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