Sanofi CD38 Antibody Sarclisa Was Approved By The European Union

- Jun 13, 2020-

Sanofi recently announced that the European Commission (EC) has approved the CD38 targeting antibody drug Sarclisa (isatuximab), combined with pomalidomide and dexamethasone (pom-dex), for the treatment of previously received at least 2 Adult patients with multiple therapies (including lenalidomide and a proteasome inhibitor), and relapsed and refractory multiple myeloma (RRMM) that showed disease progression during the last therapy.

Sarclisa is a monoclonal antibody (mAb) that binds to a specific epitope on the CD38 receptor of multiple myeloma (MM) cells. Data from the first randomized phase III trial (ICARIA-MM) showed that Sarclisa combined with pom-dex treatment significantly reduced the risk of disease progression or death by 40% compared to pom-dex treatment.

In the United States, Sarclisa was approved in early March of this year in combination with pom-dex for RRMM adult patients who have previously received at least 2 therapies (including lenalidomide and proteasome inhibitors). In addition, Sarclisa combined with pom-dex treatment plan has also been approved by Switzerland, Canada and Australia.

Multiple myeloma (MM) is the second most common blood cancer, with more than 138,000 newly diagnosed cases worldwide each year. In Europe, about 40,000 new cases are diagnosed each year; in the United States, 32,000 cases are diagnosed each year. Despite the available treatments, MM is still an incurable malignant tumor and is associated with a severe burden on patients. Because MM cannot be cured, most patients will eventually relapse and no longer respond to the currently available therapies. Sarclisa combined with pomalidomide and dexamethasone (pom-dex) regimen will provide these patients with an important new treatment option.

Dr. John Reed, Sanofi’s head of global research and development, said: "The approval of Sarclisa by the European Commission represents an important additional treatment option that may develop a new one for patients with relapsed and refractory myeloma who require new effective therapies. Standards of care. Clinical data shows that in patients who have failed at least two therapies, Sarclisa combined with pom-dex treatment extends progression-free survival by 5 months compared to pom-dex treatment."


The approval is based on data from the key Phase III ICARIA-MM study. This is a randomized, open-label, multi-center study conducted in 96 centers in 24 countries. A total of 307 RRMM patients were enrolled. These patients had previously received multiple (median 3) anti-myeloma treatments. Include at least 2 consecutive cycles of lenalidomide and proteasome inhibitors alone or in combination. In the study, isatuximab was administered by intravenous infusion at a dose of 10 mg/kg, once a week for 4 weeks, then every other week, and was used in combination with a standard dose of pom-dex during the treatment period.

This study is the first phase III study to evaluate the positive results of the Sarclisa combined standard of care (pomidol + dexamethasone, pom-dex) regimen. It included relapsed and refractory multiples that are particularly difficult to treat and have a poor prognosis. For patients with sexual myeloma, this reflects real-world clinical practice.

The results showed that in these patients, the combined treatment of Sarclisa and pom-dex significantly prolonged the progression-free survival of the disease compared to standard care (pomidol + dexamethasone, pom-dex) (median PFS: 11.53 Months vs. 6.47 months), the risk of disease progression or death was significantly reduced by 40% (HR=0.596; 95%CI: 0.44-0.81; p=0.001), and the overall response rate was significantly improved (ORR: 60.4% vs 35.3%, p <0.0001).

In addition, in additional analysis, Sarclisa and pom-dex combined treatment showed consistent therapeutic benefits in specific subgroups reflecting real-world practice compared to pom-dex, including high-risk cytogenetics patients, age ≥75 years Patients, renal insufficiency patients, lenalidomide refractory patients.

In terms of safety, Sarclisa's most common adverse reactions (occurring in 20% or more patients) are neutropenia (46.7%), infusion reactions (38.2%), pneumonia (30.9%), upper respiratory tract infection (28.3 %), diarrhea (25.7%) and bronchitis (23.7%). The most common serious adverse reactions were pneumonia (9.9%) and febrile neutropenia (6.6%).

Dr. Philippe Moreau, MD, Department of Hematology, Nantes University Hospital, France, said: "As patients experience multiple myeloma recurrence or become refractory to current therapies, they become more and more difficult to treat, and the prognosis is getting worse. At ICARIA -In the MM trial, Sarclisa combination therapy showed consistent treatment effects in the subgroup of relapsed and refractory multiple myeloma. Sarclisa provides an important new treatment plan and potential new treatment for patients with relapsed and refractory diseases Standard of care."

safety of Sarclisa

Sarclisa's active pharmaceutical ingredient isatuximab is an IgG1 chimeric monoclonal antibody that targets specific epitopes on the CD38 receptor of plasma cells and can trigger a variety of unique mechanisms of action, including the promotion of programmed tumor cell death (apoptosis) and immunity Regulate activity. CD38 is expressed at high levels on multiple myeloma (MM) cells and is a cell surface receptor target for antibody therapy in MM and other malignant tumors. In the United States and the European Union, isatuximab has been granted orphan drug status for R/R MM. Currently, Sanofi is also evaluating the potential of isatuximab in the treatment of other hematological malignancies and solid tumors.

Sarclisa will become the first direct competitor of Johnson & Johnson's heavyweight CD38 targeted drug Darzalex after its launch. The latter was launched in 2015, with global sales reaching US$2.998 billion in 2019, an increase of 48.0% from the previous year. Wall Street Investment Bank Jefferies analysts expect Sarclisa’s annual sales peak to exceed $1 billion after its listing.

Currently, Sanofi is advancing multiple phase III clinical studies to evaluate isatuximab in combination with currently available standard therapies for the treatment of RRMM patients or newly diagnosed MM patients.