B-W SHOULD ASSESS WELLBUTRIN SEIZURE RATES v. CIBA-GEIGY's TOFRANIL, FDA's PSYCHOPHARMACOLOGIC DRUGS CMTE. RECOMMENDS; STUDY COULD DETERMINE REMARKETING

Executive Summary

Burroughs Wellcome should conduct a safety study comparing Wellbutrin (bupropion HCl) to imipramine (Ciba-Geigy's Tofranil) to asses the seizure rate of bupropion, FDA's Pyschopharmacologic Drugs Advisory Cmte. recommended at its April 25 meeting. The cmte. agreed that a study proposed by B-W would be adequate to assess the safety of Wellbutrin. The study would compare the incidence of seizures in 5,600 patients randomized to receive either bupropion or imipramine. B-W voluntarily withdrew the antidepressant in March, after a study in bulemic patients found an increased incidence of seizures (8% v. less than 0.5% during clinical investigations). FDA indicated that Wellbutrin's re-introduction to the market could hinge on the results of the proposed study. Drug Research & Review Office Director Robert Temple, MD, told the cmte. that the bulemic study, as "weak and hard to interepret as it may be," leads FDA "at least preliminarily" to "doubt the sureness of our original estimate of the rate of seizures." Agency reviewers "don't think they should proceed to marketing" unless the original seizure rate estimate can be confirmed, Temple added. The cmte. generally concurred with FDA's decision that remarketing should be postponed until the proposed study is completed and evaluated. The lone exception was cmte. member Sheldon Preskorn, MD, University of Kansas, who contended: "Bulemics are a special population, and I personally don't think the risk is any higher than what it was previously." Preskorn suggested the product be allowed back on the market with "restricted labeling." A "prudent" policy would entail "good post-marketing surveillance to try to find out what are the additional risk factors," he reasoned, adding: "Another concern is . . . that we may discourage drug development of novel compounds to treat a condition which is not innocuous." B-W indicated that its proposed study was not planned by the firm to be a prerequisite to remarketing because the overall incidence of seizures was not changed by the addition of the bulemic patients to the data base. "Given what we feel about the seizure rate, we'd be interested in marketing the drug now," the company's product manager told the cmte. "We would be interested in doing the study, which by the way we had planned anyway after the drug was initially marketed, because I think it's going to be difficult for us to get the labeling changed [from second-line to first-line therapy] without such a controlled study."