Regulatory Decision Summary for VISANNE
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
Visanne is indicated for the management of pelvic pain associated with endometriosis. This supplemental submission was filed to include the use of Visanne by adolescents <18 years of age, after onset of menarche.
Why was the decision issued?
The use of Visanne for the treatment of endometriosis in adolescents was supported by Study 13788 (VISADO), a multicentre, open-label, single-arm study designed to investigate the safety and efficacy of daily oral administration of 2 mg Visanne tablets in post-menarche adolescents (12 to 18 years old) over a treatment period of 52 weeks (plus 4 weeks follow-up). A total of 111 patients were clinically suspected or confirmed to have endometriosis. Serum levels of dienogest (Visanne) from 99 patients in Study 17388 were used in a modelling and simulation pharmacokinetic study, to show that there were similar drug exposures between adolescents and adults.
Treatment of the adolescent group with 2 mg Visanne daily demonstrated decreases in both endometriosis-related pain, assessed by a visual analog scale (VAS), and endometriosis-related symptoms (pelvic pain, dysmenorrhea, and dyspareunia) assessed by the Biberoglu & Behrman Severity Profile. During the 52 weeks of treatment, the intensity of the symptoms decreased over time. The number of bleeding/ spotting days, bleeding days and bleeding/spotting episodes also decreased during this time.
Following the 52 weeks of treatment with Visanne, there was a decrease in mean bone mineral density (BMD) of the lumbar spine (L2-L4) of -1.2% in comparison to baseline. A group of adolescents with a decrease in BMD at end of treatment (EOT) showed a tendency to recovery from -2.3% at EOT to -0.6% at 6 months after EOT. Noting the potential detrimental effect that BMD loss or even plateauing of bone accretion during adolescence could have on a womans future bone health, clear labelling regarding these issues was added in the Product Monograph (PM), including a Serious Warnings and Precautions box and a recommendation for BMD monitoring.
The data reviewed in this submission indicate that the benefit/risk profile of Visanne (2 mg/day) in adolescent girls is acceptable. The clinical benefits of the treatment were shown by decreases in endometriosis-related pain and endometriosis-related symptoms (pelvic pain, dysmenorrhea, and dyspareunia). The primary clinical risk identified was a decrease in BMD of the lumbar spine, which was highlighted in the Product Monograph.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.