Ezogabine: A New Drug for Seizure Control
Ezogabine: A New Drug for Seizure Control
Jacqueline French, MD, Professor of Neurology, NYU School of Medicine, and Director of the Epilepsy Study Consortium, NY, NY, was the lead author of the recently published phase 3 multicenter, double-blind study of 305 adult patients randomized to ezogabine (N = 153) 1200 mg/day (administered 3 times daily) or placebo (N = 152). A previous similar phase 3 study demonstrated effectiveness at lower doses of 600 mg/day and 900 mg/day.
Martin Brodie, MD, Professor of Medicine and Clinical Pharmacology at the University of Glasgow, Scotland, observed, "Retigabine (ezogabine) is an interesting first-in-class antiepileptic drug, but not a breakthrough treatment."
Dr. French added, "It is early in terms of finding the 'niche' population where ezogabine will be most effective. There are many populations in which we have no experience yet. But clearly some patients with partial-onset seizures responded to this drug when they have failed a number of other drugs."
In Dr. French's study, the patients who tolerated ezogabine titration and entered the maintenance phase had a median percent reduction in seizure frequency of 54.5% vs placebo of 18.9% (P < .001). In addition, responder rates (≥ 50% reduction in total partial seizure frequency) were 55.5% for ezogabine vs 22.6% for placebo (P < .001). More than 30% of patients in the maintenance phase had > 75% seizure reduction compared with their baseline measurements. However, only 3.3% became seizure-free.
Ezogabine was first identified in 1991 by the National Institutes of Health anticonvulsant screening program where it demonstrated a broad spectrum of activity in animal models of epilepsy. Ezogabine opens KCNQ2/3 (Kv7.2/7.3) voltage-gated potassium channels on neurons and activates M-current, which regulates neuronal excitability and suppresses epileptic activity.
Phase 3 Results and Mechanism of Action
Jacqueline French, MD, Professor of Neurology, NYU School of Medicine, and Director of the Epilepsy Study Consortium, NY, NY, was the lead author of the recently published phase 3 multicenter, double-blind study of 305 adult patients randomized to ezogabine (N = 153) 1200 mg/day (administered 3 times daily) or placebo (N = 152). A previous similar phase 3 study demonstrated effectiveness at lower doses of 600 mg/day and 900 mg/day.
Martin Brodie, MD, Professor of Medicine and Clinical Pharmacology at the University of Glasgow, Scotland, observed, "Retigabine (ezogabine) is an interesting first-in-class antiepileptic drug, but not a breakthrough treatment."
Dr. French added, "It is early in terms of finding the 'niche' population where ezogabine will be most effective. There are many populations in which we have no experience yet. But clearly some patients with partial-onset seizures responded to this drug when they have failed a number of other drugs."
In Dr. French's study, the patients who tolerated ezogabine titration and entered the maintenance phase had a median percent reduction in seizure frequency of 54.5% vs placebo of 18.9% (P < .001). In addition, responder rates (≥ 50% reduction in total partial seizure frequency) were 55.5% for ezogabine vs 22.6% for placebo (P < .001). More than 30% of patients in the maintenance phase had > 75% seizure reduction compared with their baseline measurements. However, only 3.3% became seizure-free.
Unique Mechanism of Action
Ezogabine was first identified in 1991 by the National Institutes of Health anticonvulsant screening program where it demonstrated a broad spectrum of activity in animal models of epilepsy. Ezogabine opens KCNQ2/3 (Kv7.2/7.3) voltage-gated potassium channels on neurons and activates M-current, which regulates neuronal excitability and suppresses epileptic activity.
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