Sanofi recently announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive review opinion recommending the approval of the CD38-targeted antibody drug Sarclisa (isatuximab), combined with carfilzomib, Kyprolis® and dexamethasone ( Kd), for the treatment of adult patients with relapsed multiple myeloma (MM) who have received at least one therapy in the past. Now, the CHMP's opinions will be submitted to the European Commission (EC) for review, which will usually make a final review decision within the next 2 months.

　　At present, Sarclisa has been approved in the European Union, combined with pomalidomide and dexamethasone (pom-dex), for the treatment of relapses that have received at least 2 therapies in the past (including lenalidomide and proteasome inhibitors) And adult patients with refractory MM.

　　The regulatory application of Sarclisa in combination with carfilzomib and dexamethasone (S-Kd) is based on the positive results of the Phase III IKEMA clinical trial. The data shows that compared with the carfilzomib+dexamethasone regimen (Kd), the Sarclisa+carfilzomib+dexamethasone (S-Kd) regimen will statistically significantly extend the progression-free survival (PFS) and improve The risk of disease progression or death was significantly reduced by 47%, and showed a clinically significant deep remission (minus residual disease [MRD] negative rate: 29.6% vs 13%).

　　IKEMA (NCT03275285) is a randomized, multicenter, open-label phase III clinical trial that enrolled 302 patients with relapsed and/or refractory multiple myeloma (MM) in 69 clinical centers in 16 countries. These The patient had previously received 1-3 anti-myeloma therapies. During the trial, Sarclisa was infused intravenously at a dose of 10 mg/kg, once a week for four weeks, and then infused every other week. The dose of carfilzomib was 20/56 mg/m2 twice a week. The standard dose was used during the treatment. Dexamethasone. The primary endpoint of the IKEMA trial is progression-free survival (PFS). Secondary endpoints include overall response rate (ORR), good partial response or better response (≥VGPR), minimal residual disease (MRD), complete response rate (CR), overall survival (OS), and safety.

　　The results showed that the study reached the primary endpoint: Compared with the Kd group (n=123), the S-Kd group (n=179) had a 47% reduction in the risk of disease progression or death (HR=0.531, 99%CI: 0.318-0.889) , P=0.0007), PFS was significantly prolonged (median PFS: not reached vs 19.15 months). Compared with Kd, the S-Kd regimen showed consistent treatment effects in multiple subgroups. In terms of secondary endpoints, there was no statistically significant difference in ORR between the S-Kd group and the Kd group (86.6% vs 82.9%; p=0.1930). The complete response rate (CR) of S-Kd group was 39.7%, and that of Kd group was 27.6%. The VGPR of S-Kd group was 72.6%, and that of Kd group was 56.1%. The MRD-negative complete remission rate of S-Kd group was 29.6%, and that of Kd group was 13%, indicating that nearly 30% of patients in S-Kd group could not detect multiple myeloma cells using next-generation sequencing at a sensitivity of 1/100,000. At the time of the interim analysis, overall survival (OS) data were not yet mature. In this study, the safety and tolerability of Sarclisa were consistent with the safety characteristics of Sarclisa observed in other clinical trials, and no new safety signals were observed.

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