Regulatory Decision Summary for KYLEENA

The contraceptive efficacy of Kyleena was evaluated in a clinical trial that enrolled 1,452 generally healthy women aged 18-35. The Pearl Index (PI) was the primary efficacy endpoint used to assess contraceptive reliability. The Year 1 Pearl Index (PI) based on 2 pregnancies was 0.16. The cumulative 5-year probability of getting pregnant rate based on 13 pregnancies was 1.4%.

Kyleena safety data comes from two multi-center contraceptive trials: a phase II study with a 3-year duration and a phase III study with a 3-year duration and an optional extension of Kyleena use up to 5 years. In total for both studies, 1,425 subjects were exposed for at least 1 year, and 550 subjects completed 5 years of use. In the combined studies, 22% discontinued prematurely due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were increased bleeding (4.5%), abdominal pain/pelvic pain (4.2%), device expulsion (3.1%), acne/seborrhea (2.3%), and dysmenorrhea/uterine spasm (1.3%). In the clinical trials, serious adverse reactions occurring in more than a single subject included: ectopic pregnancy/ruptured ectopic pregnancy (10 subjects); pelvic inflammatory disease (6 subjects); missed abortion/incomplete spontaneous abortion/spontaneous abortion (4 subjects); ovarian cyst (3 subjects); abdominal pain (4 subjects); depression/affective disorder (4 subjects); and uterine perforation/embedded device (myometrial perforation) (3 subjects).

Approximately one-half of pregnancies that occur with Kyleena in place are likely to be ectopic. The incidence of ectopic pregnancy in clinical trials with Kyleena, which excluded women with a history of ectopic pregnancy, was approximately 0.2% per year. The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use Kyleena is unknown.

In general, the adverse reactions profile of Kyleena is comparable to other approved IUS. For the authorization of this medicinal product, the adverse events and uncertainties are addressed by adequate labelling in the product monograph and by RMP (risk management plan) risk management strategies. Based on the review of the data, the overall Benefit-Harm-Uncertainty assessments is deemed to be favourable.