Role of new Keppra analog uncertain

SEATTLE – UCB will likely submit brivaracetam – its follow-up to levetiracetam – to the Food and Drug Administration for approval in the not-so-distant future.

Brivaracetam is a molecular analog of levetiracetam (Keppra), a widely used epilepsy drug that’s now available as a generic. The company has reported that it binds synaptic vesicle protein 2A with greater affinity than does levetiracetam, which suggests greater potency. However, phase III testing compared brivaracetam to placebo, so it’s unclear if the analog has advantages over the older drug, according to Dr. Pavel Klein, an epileptologist and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md.

“Levetiracetam is a great medication, but its psychiatric side effects,” which can include aggression, depression, and even psychosis, are “limiting. If brivaracetam turns out to be a friendlier version of levetiracetam, that would be helpful, but we don’t know that yet,” he said at the annual meeting of the American Epilepsy Society.

Dr. Klein was the principal investigator on brivaracetam’s final phase III trial, and he presented the results at the meeting. With testing complete, UCB said it plans to submit brivaracetam to the FDA in early 2015.

His study randomized 768 adult patients with refractory partial onset seizures to placebo or 100 or 200 mg/day brivaracetam by mouth for 12 weeks as an adjunct; the subjects were also taking one or two other antiepileptic drugs, although not levetiracetam; the trial excluded patients taking levetiracetam and those who had taken it within 3 months. The study group was about 40 years old on average, and evenly split between men and women.

Brivaracetam 100 mg/day reduced 28-day adjusted seizure frequency by 22.8% over placebo, and 200 mg/day reduced it 23.2% over placebo. The responder rate – a reduction of at least 50% in seizure frequency – was 21.6% for placebo, 38.9% for brivaracetam 100 mg, and 37.8% for brivaracetam 200 mg. About 4.5% of brivaracetam patients went the entire 12 weeks without a seizure, versus less than 1% in the placebo group.

“Efficacy was seen in both levetiracetam-naive patients and patients previously exposed to levetiracetam, but there wasn’t really any significant difference in efficacy between the 100- and 200-mg doses. Neither was superior,” Dr. Klein said.

The efficacy outcomes are comparable to levetiracetam’s phase III results against placebo, as described in the older drug’s FDA labeling. However, brivaracetam seems to help some patients at a smaller dose, which is a potential selling point for UCB.

The study dropout rate was 6.5% for placebo patients and about 11% in the brivaracetam group. About two-thirds of brivaracetam patients reported side effects, most commonly – and also similar to levetiracetam – somnolence, dizziness, and fatigue.

Self-reported “irritability occurred relatively little” in the study, perhaps in about 2% of brivaracetam patients and 1% of the placebo group. Postmarketing data shows that irritability occurs in “somewhere around 10%” of levetiracetam patients, Dr. Klein said.

The earlier phase III trials also compared brivaracetam against placebo as an adjunct, but mostly at smaller doses; the results for 100 and 200 mg tended to be more robust.

UCB funded the work. Dr. Klein said he investigated the drug on the company’s behalf. He is also a speaker and adviser for UCB.

aotto@frontlinemedcom.com

SEATTLE – UCB will likely submit brivaracetam – its follow-up to levetiracetam – to the Food and Drug Administration for approval in the not-so-distant future.

Brivaracetam is a molecular analog of levetiracetam (Keppra), a widely used epilepsy drug that’s now available as a generic. The company has reported that it binds synaptic vesicle protein 2A with greater affinity than does levetiracetam, which suggests greater potency. However, phase III testing compared brivaracetam to placebo, so it’s unclear if the analog has advantages over the older drug, according to Dr. Pavel Klein, an epileptologist and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md.

“Levetiracetam is a great medication, but its psychiatric side effects,” which can include aggression, depression, and even psychosis, are “limiting. If brivaracetam turns out to be a friendlier version of levetiracetam, that would be helpful, but we don’t know that yet,” he said at the annual meeting of the American Epilepsy Society.

Dr. Klein was the principal investigator on brivaracetam’s final phase III trial, and he presented the results at the meeting. With testing complete, UCB said it plans to submit brivaracetam to the FDA in early 2015.

His study randomized 768 adult patients with refractory partial onset seizures to placebo or 100 or 200 mg/day brivaracetam by mouth for 12 weeks as an adjunct; the subjects were also taking one or two other antiepileptic drugs, although not levetiracetam; the trial excluded patients taking levetiracetam and those who had taken it within 3 months. The study group was about 40 years old on average, and evenly split between men and women.

Brivaracetam 100 mg/day reduced 28-day adjusted seizure frequency by 22.8% over placebo, and 200 mg/day reduced it 23.2% over placebo. The responder rate – a reduction of at least 50% in seizure frequency – was 21.6% for placebo, 38.9% for brivaracetam 100 mg, and 37.8% for brivaracetam 200 mg. About 4.5% of brivaracetam patients went the entire 12 weeks without a seizure, versus less than 1% in the placebo group.

“Efficacy was seen in both levetiracetam-naive patients and patients previously exposed to levetiracetam, but there wasn’t really any significant difference in efficacy between the 100- and 200-mg doses. Neither was superior,” Dr. Klein said.

The efficacy outcomes are comparable to levetiracetam’s phase III results against placebo, as described in the older drug’s FDA labeling. However, brivaracetam seems to help some patients at a smaller dose, which is a potential selling point for UCB.

The study dropout rate was 6.5% for placebo patients and about 11% in the brivaracetam group. About two-thirds of brivaracetam patients reported side effects, most commonly – and also similar to levetiracetam – somnolence, dizziness, and fatigue.

Self-reported “irritability occurred relatively little” in the study, perhaps in about 2% of brivaracetam patients and 1% of the placebo group. Postmarketing data shows that irritability occurs in “somewhere around 10%” of levetiracetam patients, Dr. Klein said.

The earlier phase III trials also compared brivaracetam against placebo as an adjunct, but mostly at smaller doses; the results for 100 and 200 mg tended to be more robust.

UCB funded the work. Dr. Klein said he investigated the drug on the company’s behalf. He is also a speaker and adviser for UCB.

aotto@frontlinemedcom.com

SEATTLE – UCB will likely submit brivaracetam – its follow-up to levetiracetam – to the Food and Drug Administration for approval in the not-so-distant future.

Brivaracetam is a molecular analog of levetiracetam (Keppra), a widely used epilepsy drug that’s now available as a generic. The company has reported that it binds synaptic vesicle protein 2A with greater affinity than does levetiracetam, which suggests greater potency. However, phase III testing compared brivaracetam to placebo, so it’s unclear if the analog has advantages over the older drug, according to Dr. Pavel Klein, an epileptologist and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md.

“Levetiracetam is a great medication, but its psychiatric side effects,” which can include aggression, depression, and even psychosis, are “limiting. If brivaracetam turns out to be a friendlier version of levetiracetam, that would be helpful, but we don’t know that yet,” he said at the annual meeting of the American Epilepsy Society.

Dr. Klein was the principal investigator on brivaracetam’s final phase III trial, and he presented the results at the meeting. With testing complete, UCB said it plans to submit brivaracetam to the FDA in early 2015.

His study randomized 768 adult patients with refractory partial onset seizures to placebo or 100 or 200 mg/day brivaracetam by mouth for 12 weeks as an adjunct; the subjects were also taking one or two other antiepileptic drugs, although not levetiracetam; the trial excluded patients taking levetiracetam and those who had taken it within 3 months. The study group was about 40 years old on average, and evenly split between men and women.

Brivaracetam 100 mg/day reduced 28-day adjusted seizure frequency by 22.8% over placebo, and 200 mg/day reduced it 23.2% over placebo. The responder rate – a reduction of at least 50% in seizure frequency – was 21.6% for placebo, 38.9% for brivaracetam 100 mg, and 37.8% for brivaracetam 200 mg. About 4.5% of brivaracetam patients went the entire 12 weeks without a seizure, versus less than 1% in the placebo group.

“Efficacy was seen in both levetiracetam-naive patients and patients previously exposed to levetiracetam, but there wasn’t really any significant difference in efficacy between the 100- and 200-mg doses. Neither was superior,” Dr. Klein said.

The efficacy outcomes are comparable to levetiracetam’s phase III results against placebo, as described in the older drug’s FDA labeling. However, brivaracetam seems to help some patients at a smaller dose, which is a potential selling point for UCB.

The study dropout rate was 6.5% for placebo patients and about 11% in the brivaracetam group. About two-thirds of brivaracetam patients reported side effects, most commonly – and also similar to levetiracetam – somnolence, dizziness, and fatigue.

Self-reported “irritability occurred relatively little” in the study, perhaps in about 2% of brivaracetam patients and 1% of the placebo group. Postmarketing data shows that irritability occurs in “somewhere around 10%” of levetiracetam patients, Dr. Klein said.

The earlier phase III trials also compared brivaracetam against placebo as an adjunct, but mostly at smaller doses; the results for 100 and 200 mg tended to be more robust.

UCB funded the work. Dr. Klein said he investigated the drug on the company’s behalf. He is also a speaker and adviser for UCB.

aotto@frontlinemedcom.com