Regulatory Decision Summary for Evenity

The benefits of Evenity (romosozumab) in the target patient population were demonstrated in two large pivotal clinical trials. Study 20070337 compared Evenity (N = 3589) to placebo (N = 3591) for 12 months (followed by open-label denosumab to Month 24), and Study 20110142 compared Evenity to oral alendronate for 12 months (followed by open-label alendronate to Month 24). The primary endpoints of the studies were achieved in both studies. In the placebo-controlled study, Evenity reduced the incidence of new vertebral fractures through Month 12; this reduction in risk of fracture persisted through Month 24 in patients who received Evenity during the first year. In the alendronate-controlled study, Evenity reduced the incidence of new vertebral fracture at Month 24 and the risk of clinical fractures through the primary analysis period. Evenity also increased bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck compared with placebo at Month 12. The results were clinically meaningful and statistically significant in both studies.

The Evenity safety database includes over 7,500 subjects who received at least 1 dose of romosozumab, of which over 5,700 subjects received romosozumab for at least 12 months. Adverse events that were reported more commonly in Evenity-treated patients compared to control include hypocalcemia, major adverse cardiovascular events (MACE; defined as non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death), atypical femoral fracture, osteonecrosis of the jaw, injection site reactions, serious infections and infestations, cataracts and hyperlipidemia/dyslipidemia. During the 12-month double-blind treatment period of Study 20110142, an imbalance in MACE was observed. Positively-adjudicated MACE were reported in 41 (2.0%) of Evenity-treated patients and 22 (1.1%) of alendronate-treated patients. The effect was driven primarily by myocardial infarction and stroke events. A similar imbalance was not observed during the 12-month double-blind treatment period of Study 20070337.

The imbalance in MACE in Study 20110142, along with the remaining uncertainty regarding the baseline risk in the target patient population, support risk minimization strategies implemented through product monograph labelling and pharmacovigilance activities. Information in the Serious Warnings and Precautions Box indicates that Evenity may increase the risk of myocardial infarction, stroke, and cardiovascular death, and is not recommended in patients with a history of myocardial infarction or stroke. The sponsor is required to conduct a post-marketing cardiovascular risk study in Evenity-treated patients; the study results will be communicated to Health Canada. Periodic benefit/risk evaluation reports will be submitted to MHPD for the first three years post-marketing.

Overall, based on the clinical data provided and with the risk minimization measures implemented, the benefits of Evenity outweigh its risks in the target patient population.

For more information on Health Canadas decision, please view the Summary Basis of Decision.