April 19 2021: “The European Commission approved Sarclisa® (isatuximab) in combination with carfilzomib and dexamethasone (Kd) for the treatment of adult patients with relapsed multiple myeloma who have received at least one prior therapy.
This marks the second EC approval of Sarclisa in combination with a standard of care regimen in less than 12 months.
“As there is no cure for multiple myeloma and patients often experience disease relapse, we must persist in our pursuit for additional treatment options. Nearly 30% of patients treated with the Sarclisa regimen had a profound response with undetectable levels of multiple myeloma,” said Philippe Moreau, M.D., Department of Hematology, University Hospital of Nantes, France.
“This new therapeutic regimen has the potential to become a standard of care for patients with relapsed multiple myeloma, who now have another treatment option earlier in the progression of their disease.”
This EC approval closely follows the U.S. Food and Drug Administration (FDA) approval of Sarclisa for a similar indication in March 2021.
In June 2020, Sanofi announced Sarclisa received EC approval in combination with another standard of care regimen, pomalidomide and dexamethasone (pom-dex), for the treatment of adult patients with relapsed and refractory MM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy.
“The EC approval of Sarclisa in combination with carfilzomib and dexamethasone means patients living with multiple myeloma in Europe can now receive Sarclisa in combination with two standard of care treatment regimens,” said Peter C. Adamson, Global Development Head, Oncology and Pediatric Innovation at Sanofi.
“The carfilzomib and dexamethasone combination represents an important standard of care in Europe.
The Phase 3 IKEMA trial’s finding that the addition of Sarclisa to this regimen reduced the risk of progression or death by nearly half formed the basis for this important EC approval.”
Sarclisa Efficacy and Safety Profile in Difficult-to-Treat Patients
This approval is based on data from the Phase 3 IKEMA study, a randomized, multi-center, open label clinical trial that enrolled 302 patients with relapsed MM across 69 centers spanning 16 countries.
The primary endpoint of IKEMA was progression free survival (PFS).
While median PFS, defined as time to disease progression or death, for Kd was 19.15 months, the median PFS for patients receiving Sarclisa added to carfilzomib and dexamethasone (Sarclisa combination therapy; n=179) had not been reached at the time of the pre-planned interim analysis.
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Sarclisa combination therapy reduced the risk of disease progression or death by 47% (hazard ratio 0.531, 99% CI 0.318-0.889, p=0.0007) versus standard of care Kd alone in patients with MM.
Secondary endpoints of the IKEMA trial assessed the depth of response for Sarclisa combination therapy compared to Kd, including overall response rate (ORR), complete response (CR), very good partial response (VGPR) and minimal residual disease (MRD)-negative response.
The ORR remained similar for each arm at 86.6% for the Sarclisa combination therapy versus 82.9% for Kd but was not statistically significant.
The rate of CR was 39.7% in the Sarclisa combination therapy arm and 27.6% in the Kd arm. The rate of VGPR or better was 72.6% for patients receiving Sarclisa combination therapy and 56.1% for patients receiving Kd.
MRD-negativity was observed in 29.6% of patients in the Sarclisa combination therapy arm versus 13% of patients in the Kd arm, indicating that nearly 30% of patients treated with Sarclisa combination therapy achieved undetectable levels of MM at 10-5 sensitivity as measured by next generation sequencing (NGS).
At the time of the interim analysis, overall survival (OS) data were still immature.
The most frequent adverse reactions (≥20%) were infusion reactions (45.8%), hypertension (36.7%), diarrhea (36.2%), upper respiratory tract infection (36.2%), pneumonia (28.8%), fatigue (28.2%), dyspnea (27.7%), insomnia (23.7%), bronchitis (22.6%), and back pain (22.0%).
Serious adverse reactions occurred in 59.3% of patients receiving Sarclisa combination therapy and in 57.4% of patients receiving Kd. The most frequent serious adverse reaction was pneumonia (21.5%).”
https://www.sanofi.com/en/media-room/press-releases/2021/2021-04-19-07-00-00-2212005
