Top-line results of a phase 3 trial (NCT01747915) examining the safety and efficacy of pregabalin (Lyrica; Pfizer) indicate that the drug may not be an effective adjunctive treatment for primary generalized tonic-clonic seizures.

Pfizer reported that the study did not meet its primary endpoint, with no statistically significant reduction in seizure frequency recorded with pregabalin versus placebo.

“Pfizer is committed to the study of patient populations with unmet treatment needs, including pediatric and adult patients experiencing generalized tonic-clonic seizures,” said Juan Ovalle, MD, global chief medical officer, R&D and Medical, Upjohn, a division of Pfizer, in a statement. “These data contribute to our growing understanding of pediatric epilepsy and reflect our responsibility to advance scientific knowledge through post-marketing research.”

Lyrica is currently approved by the FDA as an adjunctive therapy for the treatment of partial onset seizures in patients with epilepsy aged 4 and older. It is also approved as a treatment for a number of other neurological disorders, including fibromyalgia, diabetic neuropathy, and nerve pain associated with spinal cord injury and shingles in adults.

Lyrica has been evaluated as adjunctive therapy in epilepsy in 6 clinical trials. The study to evaluate the drug in primary generalized tonic-clonic seizures was a 12-week, randomized, double-blind, placebo-controlled, phase 3 study that evaluated 2 doses of pregabalin in 219 patients aged 5 to 65 years with primary generalized tonic-clonic seizures. Patients were randomly assigned to receive either 5 mg/kg/day of pregabalin (7 mg/kg/day for subjects with body weight <30 kg; 300 mg/day for those 17 and older), 10 mg/kg/day of pregabalin (14 mg/kg/day for subjects with body weight <30 kg; 600 mg/day for those 17 and older), or placebo.

In order to be eligible for the study, participants had to have had a minimum of 3 primary generalized tonic-clonic seizures during the 8-week baseline phase, and had to be receiving adequate and stable dosing of 1 to 3 other antiepileptic treatments. Patients with febrile seizures, focal seizures, Lennox-Gastaut syndrome, Dravet syndrome, or BECTs, as well as those with a history of status epilepticus within the prior year, were excluded from the study.

Primary endpoints included the percent reduction in 28-day seizure rate for primary generalized tonic-clonic seizures versus placebo, and percent reduction in participant and/or caregiver-reported primary generalized tonic-clonic seizure rate, as reported in a daily seizure diary.

Secondary endpoints included responder rate, indicated as the proportion of participants who had at least a 50% reduction in 28-day seizure rate calculated from baseline to the end of the study (up to 21 weeks), as well as from data collected via the daily seizure diary.
Pfizer announces top-line results from phase 3 trial of Lyrica® (pregabalin) in primary generalized tonic-clonic seizures [news release]. New York, NY: Pfizer Inc. May 24, 2019. Accessed June 3, 2019.