Sanofi announced the U.S. FDA has approved Sarclisa (isatuximab-irfc) in combination with pomalidomide and dexamethasone (pom-dex) for the treatment of adults with relapsed refractory multiple myeloma (RRMM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Sarclisa is expected to be available to patients in the U.S. shortly.
The FDA approval of Sarclisa was based on data from the randomized Phase 3 trial, ICARIA-MM. The trial was designed to demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose dexamethasone in the prolongation of Progression-Free Survival (PFS) as compared to pomalidomide and low-dose dexamethasone in patients with RRMM. In the study, Sarclisa added to pom-dex (Sarclisa combination therapy) demonstrated a statistically significant improvement in progression-free survival (PFS) with a median PFS of 11.53 months compared to 6.47 months with pom-dex alone. Sarclisa combination therapy also demonstrated a significantly greater overall response rate compared to pom-dex alone (60.4% vs. 35.3%).
The most common adverse reactions (occurring in 20% or more of patients) in patients who received Sarclisa combination therapy were neutropenia (96%), infusion-related reactions (39%), pneumonia (31%), upper respiratory tract infection (57%) and diarrhea (26%). Serious adverse reactions that occurred in more than 5% of patients who received Sarclisa combination therapy included pneumonia (25.3%) and febrile neutropenia (12.3%). Permanent discontinuation of Sarclisa combination therapy due to an adverse reaction (Grades 3-4) occurred in 7% of patients, and 3% of patients discontinued due to an infusion-related reaction.
Sarclisa is a monoclonal antibody (mAb) that binds to the CD38 receptor on multiple myeloma cells. It is designed to induce programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based therapeutics such as Sarclisa.
Sarclisa has Orphan Drug Designation status from the FDA and the European Medicines Agency (EMA). In the second quarter of 2019, the EMA accepted for review the Marketing Authorization Application for the use of Sarclisa in combination with pom-dex for the treatment of certain patients with RRMM.
About Multiple Myeloma
Multiple myeloma is the second most common hematologic malignancy, affecting more than 130,000 patients in the United States. Approximately 32,000 Americans are diagnosed with multiple myeloma each year. Despite available treatments, multiple myeloma remains an incurable malignancy and is associated with a significant patient burden. As patients relapse, they can become refractory to therapies they have received. Relapsed (or recurrent) multiple myeloma means that the cancer returns after treatment or a period of remission. Since multiple myeloma does not have a cure, most patients will relapse at some point. Refractory multiple myeloma refers to cancer that does not respond to therapy.