Sarclisa (isatuximab) is a monoclonal antibody therapy developed by Sanofi to treat myeloma. Sarclisa targets the CD38 protein present on myeloma cells and promotes their death.
The U.S. Food and Drug Administration and the European Commission both approved Sarclisa for use in combination with Pomalyst (pomalidomide) and dexamethasone to treat adults with myeloma who failed at least two prior lines of therapy, including Revlimid (lenalidomide) and a proteasome inhibitor, and experienced disease progression on the most recent therapy.
How does Sarclisa work?
Sarclisa belongs to a class of medicines known as CD38 inhibitors. Nearly all myeloma cells have high levels of the CD38 protein on their surface. Researchers studied the activity of Sarclisa in vitro and found that its mechanism of action depends on CD38 concentration on the cancer cell.
The binding of Sarclisa to CD38 on myeloma cells triggers several mechanisms. These include apoptosis (programmed cell death), antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, all of which can kill cancer cells.
Sarclisa in clinical trials
A multinational, placebo-controlled Phase 3 clinical trial (NCT02990338) called ICARIA-MM is ongoing. The trial is assessing Sarclisa’s safety and efficacy in combination with standard treatment Pomalyst and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). All patients in the study have disease progression despite at least two prior lines therapy, including Revlimid and a proteasome inhibitor.
Initial results showed progression-free survival of 11.53 months in patients on the three-combo therapy (including Sarclisa) compared with 6.47 months in those on standard care only. The overall response rate was also significantly higher at 60% in the three-combo group compared with 35% in the standard care group. The expected completion date of the study is March 2021.
Another multinational Phase 3 trial (NCT03275285), called IKEMA, is designed much like ICARIA-MM. However, it uses Sarclisa in combination with Kyprolis (carfilzomib) and dexamethasone. Standard care here, given those randomized to a comparator group, is Kyprolis and dexamethasone. This trial is ongoing but no longer recruiting participants. Researchers expect to complete it in November 2023.
The IMROZ Phase 3 trial (NCT03319667) aims to study the benefit of Sarclisa in combination with Velcade (bortezomib), Revlimid, and dexamethasone in newly diagnosed multiple myeloma (NDMM) patients ineligible for autologous hematopoietic stem cell transplantation (AHSCT). Researchers expect to complete the ongoing and open-label trial in January 2025.
Finally, a two-part Phase 3 clinical trial (NCT03617731), GMMG HD7 is enrolling up to 662 NDMM patients in Germany who are eligible for high-dose therapy and AHSCT. Part 1 of the study will look at the benefit of adding (or not adding) Sarclisa to a combination of Revlimid, Velcade, and dexamethasone as induction therapy. Part 2 will evaluate the benefits of Sarclisa plus Revlimid, versus Revlimid alone, as maintenance therapy following AHSCT. Researchers expect to complete this ongoing trial in December 2025.
Other information
Common side effects of Sarclisa reported in clinical trials include fatigue, nausea, cough, and shortness of breath. Infusion-related reactions, anemia (low red blood cell count), thrombocytopenia (low platelet count), and neutropenia (low neutrophil count) were also present.
Last updated: June 4, 2020
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