The two other phase III trials that produced the additional data submitted to the FDA were done in Europe. One study used lacosamide dosages of 200 mg, 400 mg, or 600 mg/day, as well as placebo, and involved 418 patients. The second study used lacosamide dosages of 200 mg or 400 mg/day and placebo, and involved 485 patients. Both studies had results that were similar to those reported by Dr. Chung. The 200-mg/day dosage was significantly less effective than the higher dosages.
Lacosamide has a unique mechanism of action compared with other antiepileptic drugs. The drug's effect appears due to its inhibition of the slow phase of sodium-channel inactivation. When certain neurons are stimulated, their sodium channels are activated, and then they become inactive again. The inactivation process involves both a fast phase and slow phase. By inhibiting the slow-phase of inactivation, treatment with lacosamide prolongs the activation of sodium channels in neurons.
Lacosamide also suppresses axon regeneration. This effect is believed to be responsible for the drug's activity in reducing diabetic neuropathy. When axons are damaged by diabetic neuropathy, the neurons often regenerate, but in an abnormal way that leads to pain. Treatment with lacosamide appears to inhibit axonal regrowth, Dr. Chung said.