Abstracts

Rationale: 1.2 million Americans have epilepsy, with approximately 70% of patients experiencing partial onset seizures. Of these, over 30% are medically intractable. For those who are not surgical candidates, or who refuse or fail surgical interventions, intractable epilepsy has a significant impact on quality of life. These intractable patients underscore the importance of our on-going search for new and better treatments for epilepsy. Early access to new FDA-approved drugs can be beneficial in this regard. Methods: This investigator sought permission from UCB, Inc. to use lacosamide via a single patient IND program. The process involved an application to the FDA, who granted a waiver, and IRB approval for use of lacosamide for adjunctive therapy in individual patients with intractable partial onset seizures. Lacosamide therapy was initiated at 50 mg BID and increased by 100mg per day each week until reaching a target dose of 200 mg BID (over 4 weeks). The primary endpoints for the study were seizure reduction compred to a historical 2 month baseline and spontaneously reported adverse events. Individual patients kept seizure diaries for at least 2 months prior to initiation of adjunctive treatment with lacosamide, and for the duration of treatment. Outcome will be assessed at 1, 3 and 6 months. Results: Due to the lengthy process of approval, at the time of this abstract submission, two patients have received early access to lacosamide. Both have failed >7 prior antiepileptic medications and one is using a VNS. Both patients had daily seizures, confirmed by video-EEG monitoring. Patient #1 had a baseline seizure frequency of 81 seizures per month. Her seizure reduction was immediate. She has been seizure free since day 4 of treatment. As of this submission (d 22), she has been 19 days seizure free. Transient side effects included abdominal pain and headache, both rated moderate. Both symptoms responded to nonprescription medications. Dizziness responded to reduced rate of titration. Patient #2 had a baseline seizure frequency too high to quantify. She averaged 15 brief frontal lobe nocturnal seizures nightly and 4 or more daytime seizures. Two days prior to enrollment, she was hospitalized for 24 hours for uncontrolled cluster seizures in the daytime causing frequent falls. As of this date of submission (day 11), she has had only 1 daytime seizure (day 1 of treatment) and over 90% reduction in nocturnal seizures. She reports no side effects. Conclusions: Although these are preliminary results, the response in these two medically intractable patients is striking and encouraging. Longer follow up data will be available by the time of presentation in December. In these two patients, early access to newly FDA-approved anticonvulsant agent, lacosamide, had a significant impact on seizure control with minimal side effects and provides support for the single patient IND program. Earlier application for an IND program could allow more patients access to potentially helpful anticonvulsant drugs awaiting commercial release.