GlaxoSmithKline (GSK) announced that the Peripheral and Central Nervous System Drugs Advisory Committee to the US Food and Drug Administration (FDA) has voted favourably (10 yes, 2 no, 1 abstention, 1 absence) that there is substantial evidence of effectiveness of Lamictal XR for conversion to monotherapy in patients 13 years and older with partial seizures taking one anti-epileptic drug. The fact that the immediate release formulation of Lamictal is approved for conversion to monotherapy was an important factor in this decision regarding Lamictal XR extended-release tablets.
The Advisory Committee extensively discussed the methodology and appropriateness of using a historical control approach in trials evaluating anti-epileptic drugs for conversion to monotherapy in patients with partial seizures. The Committee voted unanimously in favour (14 yes, 0 no) that a historical control approach can be acceptable under the specific circumstance in which the drug is known to be effective as adjunctive treatment.
The Committee reviewed data from study LAM30055, an international, multicenter, historical control study evaluating 300 mg/day and 250 mg/day of Lamictal XR for conversion to monotherapy in appropriate patients. In ‘conversion to monotherapy’, an additional anti-epileptic drug is added to a patient’s existing anti-epileptic drug therapy while the original therapy is gradually withdrawn. LAM30055 used a historical control based on a pooled analysis of previously conducted conversion to monotherapy studies.
Of the 226 patients treated with Lamictal XR, eight patients reported 10 treatment-emergent serious adverse events, including one serious adverse event of rash. Other serious adverse events were seizure related, trauma, neoplasm, upper gastrointestinal haemorrhage, pyrexia and respiratory failure. No deaths were reported during the study. Four per cent of patients treated with 300 mg/day and 10 per cent treated with 250 mg/day discontinued treatment due to adverse events. The only adverse event leading to withdrawal in more than one patient was rash (n=1 in 300mg/day, n=7 in 250 mg/day group).
Treatment-emergent adverse events were reported by 53 per cent and 61 per cent of patients in the 300 mg/day and 250 mg/day groups, respectively. The most common adverse events occurring in at least 5 per cent of patients in either the 300 mg/day or 250 mg/day treatment group, respectively, were: headache (26 and 28 per cent), dizziness (11 and 9 per cent), rash (4 and 11 per cent), nasopharyngitis (6 and 6 per cent), nausea (5 and 5 per cent), somnolence (4 and 5 per cent) and insomnia (0 and 5 per cent).
An FDA Advisory Committee is convened to provide the FDA with independent expert advice on a broad range of issues. The Committee provides non-binding recommendations for consideration by FDA, with the final decision on approval made by FDA.
GSK submitted a supplemental New Drug Application to FDA seeking approval of Lamictal XR for conversion to monotherapy on March 31, 2010; the Prescription Drug User Fee Act goal date is April 30, 2011.
Lamictal XR Extended-Release tablets are approved in the US as adjunctive therapy for partial seizures and primary generalized tonic-clonic seizures in patients 13 years and older. Safety and effectiveness of Lamictal XR for use in patients less than 13 years of age have not been established.