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On April 19, the European Commission (EC) approved Sanofi Sarclisa (isatuximab, ixatuximab) in combination with carfilzomib and dexamethasone (Kd) for recurrent multiple patients who have received at least one treatment Treatment of adult patients with myeloma (MM).
This marks the second time in less than 12 months that the European Union has approved the use of Sarclisa in combination with a standard care regimen.
The EC's approval decision was made immediately following the US FDA's approval of Sarclisa for similar indications in March 2021.
In June 2020, Sanofi announced that the combination of Sarclisa and another standard care regimen, pomalidomide and dexamethasone (pom-dex), was approved by EC for the treatment of at least two previous treatments (including Nalidomide and proteasome inhibitors) and in the last treatment of relapsed refractory MM adult patients who have demonstrated disease progression.
According to Sanofi, this approval is based on data from the Phase 3 study IKEMA, which is a randomized, multi-center, open clinical trial involving 302 patients with recurrent MM from 69 centers in 16 countries.
The primary endpoint of IKEMA is progression-free survival (PFS).
Although the median PFS (defined as the time to disease progression or death) of patients in the standard treatment Kd group was 19.
15 months, the pre-planned interim analysis received Sarclisa plus carfilzomib and dexamethasone (Sarclisa combined Treatment group; n=179) The median PFS of the treated patients has not yet reached.
In MM patients, Sarclisa combination therapy reduced the risk of disease progression or death by 47% compared with standard treatment alone (hazard ratio 0.
531, 99% CI 0.
The secondary endpoints of the IKEMA trial evaluated the depth of response of Sarclisa combination therapy compared with Kd therapy, including overall response rate (ORR), complete response (CR), very good partial response (VGPR) and minimal residual disease (MRD)-negative reaction.
The ORRs of the Sarclisa combination treatment group and the Kd group were similar, 86.
6% and 82.
9%, respectively, which was not statistically significant.
The incidence of CR in the Sarclisa combination treatment group was 39.
7%, and the incidence of CR in the Kd group was 27.
6% in the combination therapy group, VGPR≥56.
1% in the Kd group.
6% of the patients in the Sarclisa combination treatment group were MRD negative, and 13% of the patients in the Kd group were MRD negative, indicating that nearly 30% of the patients in the Sarclisa combination treatment group reached a detection failure at a sensitivity of 10-5 as determined by next-generation sequencing (NGS).
To the MM level.
At the time of the interim analysis, the overall survival rate (OS) data was not yet mature.
In addition, the study found that the most common (≥20%) adverse reactions were infusion reactions (45.
8%), hypertension (36.
7%), diarrhea (36.
2%), upper respiratory tract infection (36.
2%), and pneumonia (28.
8%) ), fatigue (28.
2%), dyspnea (27.
7%), insomnia (23.
7%), bronchitis (22.
6%) and back pain (22.
The incidence of serious adverse reactions was 59.
3% and 57.
The most common serious adverse reaction is pneumonia (21.
In the Sarclisa combination treatment group and Kd treatment group, 8.
5% and 13.
9% of patients were permanently discontinued due to adverse reactions.
Among patients receiving Sarclisa combination therapy, 3.
4% of patients reported fatal adverse events, and among patients treated with Kd, 1.
6% of patients reported fatal adverse events.
Sarclisa is approved in the European Union, the United States, Switzerland, the United Kingdom, Canada, Australia, Japan, Russia, the United Arab Emirates, South Korea, Taiwan and Qatar in combination with pom-dex for the treatment of certain adult relapsed and refractory MM.
In the United States, Sarclisa's common name is isatuximab-irfc, and it is also approved to combine carfilzomib and dexamethasone in the treatment of adult patients with relapsed or refractory MM.
These patients have previously received 1-3 courses of treatment.
Reference source: European Commission approves second indication of Sarclisa® (isatuximab) for relapsed multiple myeloma