Sarclisa + Kyprolis + dexmethasone demonstrated superior progression free survival and clinically meaningful depth of response in patients with relapsed multiple myeloma. Sanofi

Sarclisa (isatuximab) added to carfilzomib and dexamethasone (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, n=179) compared to standard of care carfilzomib and dexamethasone (Kd) in patients (n=123) with relapsed multiple myeloma (MM).

Sarclisa combination therapy compared to Kd alone showed a treatment benefit consistent across multiple subgroups. These results from the Phase III IKEMA trial follow the topline announcement on May 12, 2020 that Sarclisa combination therapy met the trial primary endpoint at the pre-planned interim analysis. Interim results will be presented during the late-breaking session of the European Hematology Association (EHA) Virtual Congress (EHA25) on June 14, 2020 and will form the basis for global regulatory submissions later this year.

While median progression free survival (PFS), defined as time to disease progression or death, for Kd was 19.15 months, the median PFS for patients receiving Sarclisa combination therapy had not been reached at the time of the pre-planned interim analysis. The safety and tolerability of Sarclisa observed in this trial was consistent with the observed safety profile of Sarclisa in other clinical trials, with no new safety signals observed. The safety and tolerability of Sarclisa observed in this trial was consistent with the observed safety profile of Sarclisa in other clinical trials, with no new safety signals observed.

Depth of Disease Response with Sarclisa Combination Therapy : Secondary endpoints of the IKEMA trial examined the consistency and 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. There was no statistically significant difference in ORR, which remained similar for each arm at 86.6% for the Sarclisa combination versus 82.9% for Kd (p=0.1930). The rate of CR was 39.7% in the Sarclisa combination arm and 27.6% in the Kd arm. The rate of VGPR was 72.6% for patients receiving Sarclisa combination therapy and 56.1% for patients receiving Kd. MRD-negative complete response was observed in 29.6% of patients in the Sarclisa combination 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.

In this trial, treatment emergent adverse events (TEAEs) of Grade greater than 3 were observed in 76.8% of patients treated with Sarclisa combination therapy versus 67.2% of patients treated with Kd. Treatment-emergent serious adverse events (SAEs) and fatal TEAEs were similar in the Sarclisa combination therapy arm versus the Kd arm, reporting 59.3% versus 57.4% and 3.4% versus 3.3%, respectively. Infusion reactions were reported in 45.8% (0.6% Grade 3-4) of patients treated with Sarclisa combination therapy versus 3.3% (0% Grade 3-4) of patients treated with Kd. Respiratory infections of Grade greater than 3 were seen in 32.2% of patients in the Sarclisa combination therapy arm versus 23.8% of patients in the Kd arm, and cardiac failure Grade greater than 3 was reported in 4.0% for Sarclisa combination therapy versus 4.1% for Kd. Grade 3-4 thrombocytopenia and neutropenia were 29.9% for Sarclisa combination therapy versus 23.8% for Kd, and 19.2% for Sarclisa combination therapy versus 7.4% for Kd. Main reasons for treatment discontinuation were disease progression (29.1% for Sarclisa combination therapy versus 39.8% for Kd) and AEs (8.4% for Sarclisa combination therapy versus 13.8% for Kd).