An analysis of efficacy data from four phase III studies of botulinum neurotoxin type A-ABO for the treatment of glabellar lines.

BACKGROUND A new formulation of a botulinum neurotoxin type A (BoNTA-ABO; Dysport [abobotulinumtoxinA], Medicis Aesthetics, Scottsdale, AZ) has recently been approved in the United States for the treatment of moderate to severe glabellar lines. OBJECTIVE We describe the results of four phase III studies of BoNTA-ABO for the treatment of glabellar lines. METHODS Of the four studies reported here, three were double-blind, multicenter, randomized, placebo-controlled studies and one was an open-label extension study. A second phase III, open-label extension study is ongoing. Studies enrolled ethnically diverse, healthy adults with glabellar lines of at least moderate severity at maximum frown. Patients were followed for up to 180 days after treatment. The fixed-dose, single treatment study randomized 158 patients to receive placebo or a single 50-unit BoNTA-ABO dose. The fixed-dose, repeat treatment study enrolled 311 patients to assess treatment following repeat BoNTA-ABO treatment of 50 units. A variable-dose study randomized 816 patients to receive placebo or a single variable dose (50 to 80 units, based on gender and muscle mass assessment). The fourth phase III study was open-label to evaluate repeat dosing (50 units). Clinical evaluations were performed on days 14 and 30, and monthly thereafter. Primary efficacy endpoints were based on the investigators' and patients' assessment of glabellar line severity at day 30 using wrinkle severity rating scales. Responders were defined as patients who had a composite 2+ grade improvement in wrinkle severity, meaning that a patient had a baseline Glabellar Line Severity Scale (GLSS) score of 2 (moderate glabellar lines) and a day 30 GLSS score of 0 (no glabellar lines/none), or a baseline GLSS score of 3 (severe glabellar lines) and a day 30 GLSS score of 0 (no glabellar lines/none) or 1 (mild glabellar lines), for both the blinded investigator's and patient's assessments. RESULTS Patients (1116 total; 720 BoNTA-ABO, 396 placebo) treated with BoNTA-ABO received 50 to 80 units. The median duration of response was 85 days for fixed dosing and 109 days for variable dosing. Similar efficacy occurred at doses adjusted for gender and muscle mass, although male patients required higher doses than female patients in the variable-dose study. Responses appeared as early as 24 hours, with a median time to onset of three days. The open-label extension study evaluated 1200 patients for 13 months. Maintenance of efficacy was seen after multiple treatment cycles, indicating that patients did not develop a tolerance. A second open-label study is ongoing and is not included in this report. CONCLUSIONS BoNTA-ABO significantly improved moderate to severe glabellar lines compared with placebo, with onset of effect seen as soon as 24 hours after treatment and a median duration of effect of 85 and 109 days for fixed and variable dosing, respectively.