Sanofi's CD38 Antibody Sarclisa Receives EU Approval for Relapsed/Refractory Multiple Myeloma, Challenging J&J's $3B Blockbuster Darzalex

June 04, 2020 /BioValleyBIOON/ -- Sanofi recently announced that the European Commission (EC) has approved the CD38-targeting antibody drug Sarclisa (isatuximab), in combination with pomalidomide and dexamethasone (pom-dex), for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have previously received at least two therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression during or after their 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) show that,Compared with pom-dex therapy, Sarclisa in combination with pom-dex therapy significantly reduced the risk of disease progression or death by 40%.

In the United States, Sarclisa was approved in early March this year, in combination with pom-dex, for adult patients with relapsed/refractory multiple myeloma (RRMM) who have previously received at least two therapies, including lenalidomide and a proteasome inhibitor. Additionally, the Sarclisa plus pom-dex regimen has also been approved in Switzerland, Canada, and Australia.

Multiple Myeloma (MM) is the second most common hematologic malignancy worldwide, with new cases annuallyDiagnosisMore than 138,000 cases. In Europe, approximately 40,000 new cases are diagnosed annually; in the United States, 32,000 cases are diagnosed each year. Despite available treatments, MM remains an incurable malignancy.Tumor, associated with a significant burden on patients. As multiple myeloma (MM) is incurable, most patients will eventually relapse and become refractory to currently available therapies. The combination of Sarclisa with pomalidomide and dexamethasone (pom-dex) regimen will provide an important new treatment option for these patients.

Dr. John Reed, Global Head of Research and Development at Sanofi, stated: “The European Commission’s approval of Sarclisa represents an important additional treatment option that may establish a new standard of care for patients with relapsed and refractory multiple myeloma who are in need of new, effective therapies. Clinical data demonstrate that, among patients who have failed at least two prior therapies, treatment with Sarclisa in combination with pom-dex extended progression-free survival by 5 months compared with pom-dex alone.”

This approval is based on data from the pivotal Phase III ICARIA-MM study. This was a randomized, open-label, multicenter study conducted at 96 centers across 24 countries, enrolling a total of 307 patients with relapsed/refractory multiple myeloma (RRMM). These patients had previously received multiple (median of 3) anti-myeloma therapies, including at least two consecutive cycles of 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 four weeks, followed by every other week dosing, in combination with standard-dose pomalidomide and dexamethasone (pom-dex) during the treatment period.

This study is the first Phase III trial to demonstrate positive outcomes with Sarclisa in combination with standard of care (pomalidomide plus dexamethasone, pom-dex), enrolling patients with relapsed and refractory multiple myeloma who are particularly difficult to treat and have a very poor prognosis, reflecting real-world clinical practice.

The results showed that, in this patient population, Sarclisa in combination with pom-dex significantly prolonged progression-free survival (median PFS: 11.53 months vs. 6.47 months), reduced the risk of disease progression or death by 40% (HR=0.596; 95% CI: 0.44–0.81; p=0.001), and significantly improved the overall response rate (ORR: 60.4% vs. 35.3%, p<0.0001) compared with standard care (pomalidomide plus dexamethasone, pom-dex).

Furthermore, in additional analyses, Sarclisa in combination with pom-dex demonstrated consistent treatment benefits compared with pom-dex alone in specific subgroups reflecting real-world practice, including high-risk cytogeneticsGeneticspatients, patients aged ≥75 years, patients with renal impairment, and lenalidomide-refractory patients.

In terms of safety, the most common adverse reactions to Sarclisa (occurring in 20% or more of patients) were neutropenia (46.7%), infusion-related reactions (38.2%), pneumonia (30.9%), upper respiratory tract infections (28.3%), diarrhea (25.7%), and bronchitis (23.7%). The most common seriousAdverse Reactionspneumonia (9.9%) and febrile neutropenia (6.6%).

Dr. Philippe Moreau, from the Department of Hematology at Nantes University Hospital in France, stated, “As patients experience relapse of multiple myeloma or become refractory to current therapies, they become increasingly difficult to treat, with progressively poorer prognoses. In the ICARIA-MM trial, Sarclisa-based combination therapy demonstrated consistent efficacy in subgroups of patients with relapsed and refractory multiple myeloma. Sarclisa provides an important new treatment option and a potential new standard of care for these patients with relapsed, refractory disease.”

The active pharmaceutical ingredient of Sarclisa, isatuximab, is an IgG1 chimeric monoclonal antibody that targets a specific epitope on the CD38 receptor of plasma cells, triggering multiple unique mechanisms of action, including the promotion 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 therapy in MM and other malignancies. In both the United States and the European Union, isatuximab has been granted orphan drug designation for the treatment of relapsed/refractory multiple myeloma (R/R MM). Currently, Sanofi is also evaluating isatuximab for the treatment of other hematologic malignancies.Tumorand the potential in solid tumors.

Upon its market launch, Sarclisa will become the first direct competitor to Johnson & Johnson’s blockbuster CD38-targeted therapy, Darzalex, which was launched in 2015 and achieved global sales of $2.998 billion in 2019, representing a 48.0% year-over-year increase. Analysts at Jefferies, a Wall Street investment bank, project that Sarclisa’s annual peak sales will exceed $1 billion following its commercialization.

Currently, Sanofi is advancing multiple Phase III clinical studies to evaluate isatuximab in combination with currently available standard therapies for the treatment of patients with RRMM or newDiagnosisMM patients. (Bioon.com)

Original Source: Sanofi European Commissionapproves Sarclisa® (isatuximab) for adults with relapsed and refractory multiple myeloma