Isatuximab (SAR-650984) is an investigational monoclonal antibody therapy being developed by Sanofi to treat multiple myeloma. Isatuximab targets the CD38 protein found on myeloma cells and promotes their death.

Isatuximab was designated an orphan drug by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2016.

The FDA has agreed to review isatuximab’s biological license application requesting its approval as a therapy for hard-t0-treat multiple myeloma. The agency’s decision is expected to be announced in April 2020.

How does isatuximab work?

Isatuximab belongs to a class of drugs known as CD38 inhibitors. Almost all myeloma cells have high levels of the CD38 protein on their surface. Researchers studied the activity of isatuximab in vitro (in the lab) and found that its mechanism of action depends on CD38 concentration on the cancer cell.

The binding of isatuximab to CD38 on myeloma cells triggers several mechanisms, including apoptosis (programmed cell death), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP), all of which can kill cancer cells.

Isatuximab in clinical trials

A multinational, placebo-controlled Phase 3 clinical trial (NCT02990338) called ICARIA-MM is ongoing. The trial will assess isatuximab’s safety and efficacy in combination with standard-of-care Pomalyst and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM).  All enrolled have disease progression despite at least two prior lines of Revlimid (lenalidomide) and a proteasome inhibitor.

Initial results showed an increase in progression-free survival to 11.53 months in patients on the three-combo therapy (including isatuximab) compared to 6.47 months in those on standard care only. The overall response rate (ORR) was also significantly higher at 60% in the three-combo group compared to 35% in the standard care group. The study is expected to end in November 2020.

Another multinational Phase 3 clinical trial (NCT03275285), called IKEMA, is designed much like ICARIA-MM but uses isatuximab 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. It is expected to finish in November 2023.

A Phase 3 clinical trial (NCT03319667) called IMROZ aims to study the benefit of isatuximab in combination with Velcade (bortezomib), Revlimid, and dexamethasone in newly diagnosed multiple myeloma (NDMM) patients ineligible for autologous hematopoietic stem cell transplantation (AHSCT). The ongoing and open-label trial is expected to be completed in January 2025.

Finally, a two-part Phase 3 clinical trial (NCT03617731) called GMMG HD7 is enrolling up to 662 NDMM patients who are eligible for high-dose therapy and AHSCT.

Part one will look at the benefit of adding (or not adding) isatuximab to a combination of Revlimid, Velcade, and dexamethasone chemotherapy as an induction treatment; part two will evaluate the benefits of isatuximab plus Revlimid, versus Revlimid  alone, as a maintenance therapy following AHSCT. This ongoing trial is expected to be completed in December 2025.

Other information

Common side effects of isatuximab 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 reported.


Last updated: Nov. 25, 2019


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