Biovail comments on Teva Pharmaceutical's proposed Budeprion XL trial

Biovail Corporation (NYSE/TSX: BVF) today commented on a proposed clinical trial recently announced by Teva Pharmaceutical Industries Ltd. According to Teva, the trial is intended to address reports of inefficacy and adverse events by consumers who switched from Wellbutrin XL^® 300 mg, Biovail’s FDA-approved brand of the antidepressant, bupropion hydrochloride, to Budeprion XL, Teva’s generic formulation of the drug. The trial was described in a Dow Jones Newswire article dated December 2, 2009.

“Even if Wellbutrin XL® and Budeprion XL were found (again) to be bioequivalent according to FDA bioequivalence criteria, the failure to find systematic differences in AUC and Cmax in the study does not exclude the possibility of other between-product differences affecting clinical response.”

Based on the limited information that has been made available about the clinical trial by Teva, Biovail believes the proposed study will not likely effectively address the complaints of consumers because it is too small in size and too brief in duration.

According to the December 2, 2009 article, the proposed study will enroll 138 patients who complained after switching from Wellbutrin XL^® 300 mg to Budeprion XL. The study purportedly will employ a “double dummy” design in which patients will receive both placebo and active doses of each product over 16 days, alternating after eight days. Patients will be confined in a clinical setting for a total period of 24 days.

A statement in the article attributed to Teva’s head of regulatory affairs suggests that the study will rely on blood-level data to verify bioequivalence of Wellbutrin XL^® and Budeprion XL. The article indicates that bioequivalence will be based on the standard statistical criteria of the U.S. Food and Drug Administration (FDA). Adverse events are also to be recorded.

Budeprion XL is already deemed to be bioequivalent to Wellbutrin XL^® by the FDA as defined by existing standard FDA criteria. Biovail believes this determination is likely to be confirmed by the proposed new trial.

However, based on available information, an independent expert retained by Biovail to consider the matter noted, “Even if Wellbutrin XL^® and Budeprion XL were found (again) to be bioequivalent according to FDA bioequivalence criteria, the failure to find systematic differences in AUC and C_max in the study does not exclude the possibility of other between-product differences affecting clinical response.”

Biovail believes the size of the proposed Teva study, while much larger than needed for bioequivalence testing, is likely too small to demonstrate that Wellbutrin XL^® 300 mg and Budeprion XL have similar safety, tolerability, and/or efficacy profiles. In addition, the eight-day treatment periods in the proposed trial may be too brief for a clinically meaningful result, since most antidepressant clinical trials require treatment periods of at least 28 days.

To meaningfully address the reports of inefficacy and adverse events, Biovail’s expert believes that a more extensive re-randomized trial should be conducted. In such a study, a larger number of subjects, both those who have and have not reported difficulties upon being switched from Wellbutrin XL^® 300 mg to Budeprion XL in the past, would be assigned to Wellbutrin XL^® and placebo Budeprion XL under double-dummy conditions. During the study, groups of subjects would be re-randomized to Budeprion XL and placebo Wellbutrin XL^®, or continued on their original treatment.

Based on the views of its outside expert, Biovail believes a much larger and differently designed trial than has been proposed by Teva is required to demonstrate what, if any, clinical differences exist between Wellbutrin XL^® 300 mg and Budeprion XL.

Biovail’s primary concern is the safety and well-being of patients.