Regulatory Decision Summary for EMPLICITI

Data from a pivotal phase 3, open-label, randomized clinical study in patients (n = 646) with multiple myeloma that received one to three prior therapies has demonstrated that Empliciti, in combination with lenalidomide and dexamethasone (E+Ld), provides superior efficacy as compared to lenalidomide and dexamethasone (Ld) alone. The co-primary objectives of the study were to demonstrate statistically significant improvements in progression free survival (PFS) and overall response rate (ORR). The point estimates for median PFS were 19.4 months and 14.9 months for the E+Ld and Ld arms, respectively. The hazard ratio for PFS was 0.70(97.61% CI: 0.55, 0.88) representing a 30% improvement in the risk of progression with the addition of Empliciti to lenalidomide to dexamethasone. The observed overall response rates were 78.5% for E+Ld treated patients and 65.5% for Ld treated patients representing a 12.6% difference in favour of E+Ld. The higher rates of response observed in the E+Ld treatment arm were also associated with an improvement in duration of response.

The safety profile of elotuzumab in combination with lenalidomide and dexamethasone is considered acceptable in the context of relapsed/refractory multiple myeloma. Overall, there were fewer deaths among E+Ld treated patients and there were also fewer deaths within 60 days of the last treatment administered. Nearly all patients enrolled in either treatment arm experienced at least 1 any grade adverse event (>99% in each arm); however, serious adverse events occurred more often among E+Ld treated patients (65.4% vs. 56.5%). In terms of specific risks, infusion reactions occurred in 10.4% of patients. Most of these reactions were mild. Additional identified risks include infection, deep vein thrombosis and pulmonary embolism, second primary malignancies and hepatotoxicity. Notably, treatment with lenalidomide/dexamethasone was prolonged in the E+Ld arm (19 vs. 14 cycles), which may have contributed to the increased rates of AEs in general and of infections, DVTs and PEs. Appropriate risk identification and management strategies have been included in the product monograph to mitigate the risk of infusion reactions and to communicate additional treatment-related risks.

The overall benefit-risk assessment for Empliciti in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma patients that have received one to three prior therapies is considered favourable. The favourable benefit-risk profile is based on robust and clinically meaningful improvements in PFS and ORR as well as a trend towards improved overall survival in combination with a safety profile that is considered acceptable and that can be managed through risk communication and mitigation measures including those implemented in the agreed upon product monograph.

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