Sanofi's CD38 Monoclonal Antibody Isatuximab Reduces Risk of Death by 40% in Relapsed/Refractory Multiple Myeloma Patients

June 21, 2019 /BioValleyBIOON/ -- French pharmaceutical giant Sanofi recently announced detailed data from the pivotal Phase III clinical trial ICARIA-MM, evaluating the CD38-targeted monoclonal antibody isatuximab for the treatment of relapsed or refractory multiple myeloma (RRMM). The results demonstrated that isatuximab in combination with pomalidomide and dexamethasone (pom-dex) significantly prolonged progression-free survival (PFS) with statistical significance compared to standard care (pom-dex), thereby meeting the study’s primary endpoint. In the second quarter of this year, the marketing application for isatuximab in combination with pom-dex for the treatment of RRMM was approved by the U.S.FDAand accepted and reviewed by the EU EMA.

Notably, the ICARIA-MM study is the first Phase III trial to demonstrate positive results with isatuximab in combination with pom-dex. Currently, Sanofi is advancing four Phase III clinical studies evaluating isatuximab in combination with currently available standard therapies for the treatment of patients with RRMM or newlyDiagnosispatients with MM. MM is the second most common hematologic malignancyTumor, globally, the annual number of new cases exceeds 1.38 million. For most patients, MM remains incurable, resulting in a significant unmet medical need in this field.

Isatuximab (SAR650984) is an IgG1 chimeric monoclonal antibody that targets a specific epitope of CD38, triggering multiple unique mechanisms of action, including the induction of programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly expressed on multiple myeloma (MM) cells and serves as a cell-surface receptor target for antibody-based therapies in MM and other malignancies. Isatuximab has been granted orphan drug designation for the treatment of relapsed/refractory multiple myeloma (R/R MM) in both the United States and the European Union. Currently, Sanofi is also evaluating isatuximab for the treatment of other hematologic malignancies.Tumorand the potential for solid tumors.

ICARIA-MM is a randomized, open-label, multicenter study conducted across 96 centers in 24 countries, enrolling a total of 307 patients with relapsed/refractory multiple myeloma (RRMM). These patients had previously received multiple (median, 3) anti-myeloma therapies, including at least two consecutive lines of treatment with lenalidomide and a proteasome inhibitor, either as monotherapy or in combination. In the study, isatuximab was administered via intravenous infusion at a dose of 10 mg/kg once weekly for 4 weeks, followed by every-other-week dosing, in combination with standard-dose pomalidomide and dexamethasone (pom-dex) throughout the treatment period.

The results showed that, compared with standard care (pom-dex), isatuximab combined with pom-dex significantly prolonged progression-free survival (median PFS: 11.53 months vs. 6.47 months; HR=0.596, 95% CI: 0.44–0.81, p=0.001) and significantly improved the overall response rate (ORR: 60% vs. 35%, p<0.0001). Treatment benefits were observed across all subgroups, including patients aged ≥75 years, those with renal impairment, and lenalidomide-refractory patients.

Furthermore, compared with pom-dex, isatuximab-based combination therapy demonstrated advantages in the following outcomes: (1) a significantly higher very good partial response (VGPR) rate (31.8% vs. 8.5%, p < 0.0001), longer duration of response (DOR: 13.27 months vs. 11.07 months), and a shorter median time to first response among patients who achieved response (35 days vs. 58 days); (2) longer time to next treatment (not reached vs. 9.1 months; HR = 0.538); and (3) a trend favoring the isatuximab combination regimen in overall survival (OS) at the time of data analysis, with final results to be reported upon data maturity.

In terms of safety, compared with the pom-dex treatment group, the isatuximab combination therapy group had a higher incidence of grade ≥3 adverse events (86.8% vs 70.5%), a lower rate of treatment discontinuation due to adverse events (7.2% vs 12.8%), a lower mortality rate due to adverse events (7.9% vs 9.4%), a higher incidence of grade ≥3 infections (42.8% vs 30.2%), and a higher incidence of grade ≥3 neutropenia (84.9% [febrile 11.8%] vs 70.1% [febrile 2.0%]). The incidence of infusion reactions in the isatuximab combination therapy group was 38.2% (2.6% were grade 3–4).

Paul Richardson, the study’s principal investigator, clinical program leader, and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, stated, “In this study, the isatuximab plus pom-dex regimen reduced the risk of disease progression or death by 40% compared with pom-dex alone. This finding is particularly noteworthy because the study enrolled a patient population that is especially difficult to treat—those with relapsed and refractory disease—which, in my view, closely reflects real-world clinical practice.” (Bioon.com)

Original source: Sanofi official website