CHMP Recommends Approval of Sanofi's Sarclisa (Isatuximab) in Combination with Carfilzomib and Dexamethasone for Relapsed Multiple Myeloma

March 05, 2021 News /BioValleyBIOON/ -- Sanofi recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the CD38-targeted antibody drug Sarclisa (isatuximab) in combination with carfilzomib (Kyprolis®) and dexamethasone (Kd regimen) for the treatment of adult patients with relapsed multiple myeloma (MM) who have received at least one prior therapy. The CHMP’s opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final decision within the next two months.

Currently, Sarclisa has been approved in the European Union, in combination with pomalidomide and dexamethasone (pom-dex), for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Regulatory Application for Sarclisa in Combination with Carfilzomib and Dexamethasone (S-Kd) Regimen, Based on the Phase III IKEMAClinical Trialpositive results. The data showed that, compared with the carfilzomib plus dexamethasone (Kd) regimen, the Sarclisa plus carfilzomib and dexamethasone (S-Kd) regimen significantly prolonged progression-free survival (PFS), reduced the risk of disease progression or death by 47%, and demonstrated clinically meaningful deep responses (minimal residual disease [MRD] negativity rate: 29.6% vs. 13%).

SanofiTumorPeter Adamson, Head of Global Development for Pediatric Innovation, stated: “Sarclisa, in combination with two standard treatment regimens, has demonstrated superior efficacy, reinforcing its potential to become the preferred anti-CD38 therapy for multiple myeloma. We look forward to collaborating with the European Commission (EC) to make Sarclisa available to more patients and are committed to researching the integration of Sarclisa into the current standards of care across all lines of treatment for multiple myeloma.”

Mechanism of Action of Isatuximab (Image source: aacrjournals.org)

IKEMA (NCT03275285) is a randomized, multicenter, open-label phase IIIClinical Trial, 302 patients with relapsed and/or refractory multiple myeloma (MM) who had previously received 1–3 prior anti-myeloma therapies were enrolled across 69 clinical centers in 16 countries. During the trial, Sarclisa was administered via intravenous infusion at a dose of 10 mg/kg once weekly for four weeks, followed by once every other week; carfilzomib was administered at a dose of 20/56 mg/m² twice weekly, and dexamethasone was used at standard doses during treatment. The primary endpoint of the IKEMA trial was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), very good partial response or better (≥VGPR), minimal residual disease (MRD), complete response rate (CR), overall survival (OS), and safety.

The results showed that the study met its primary endpoint: compared with the Kd group (n=123), the S-Kd group (n=179) demonstrated a 47% reduction in the risk of disease progression or death (HR=0.531, 99% CI: 0.318–0.889, p=0.0007), with significantly prolonged progression-free survival (median PFS: not reached vs. 19.15 months). Compared with Kd, the S-Kd regimen showed consistent treatment effects across multiple subgroups. Regarding secondary endpoints: there was no statistically significant difference between the S-Kd and Kd groups in overall response rate (ORR) (86.6% vs. 82.9%; p=0.1930). The complete response (CR) rate was 39.7% in the S-Kd group versus 27.6% in the Kd group. The very good partial response (VGPR) rate was 72.6% in the S-Kd group versus 56.1% in the Kd group. The minimal residual disease (MRD)-negative complete response rate was 29.6% in the S-Kd group versus 13% in the Kd group, indicating that nearly 30% of patients in the S-Kd group had no detectable multiple myeloma cells by next-generation sequencing at a sensitivity level of 1 in 100,000. At the time of the interim analysis, overall survival (OS) data were immature. In this study, the safety and tolerability profile of Sarclisa were consistent with those observed in otherClinical Trialconsistent with the safety profile of Sarclisa observed in , and no new safety signals were observed.

Multiple myeloma (MM) is the second most common hematologic malignancy worldwide, with new cases annuallyDiagnosisMore than 138,000 cases have been reported. In Europe, 39,000 new cases are diagnosed annually; in the United States, 32,000 new cases are diagnosed each year. Despite available treatments, multiple myeloma (MM) remains an incurable malignancy.Tumor, which is associated with a significant burden on patients. As MM is incurable, most patients eventually relapse and no longer respond to currently available therapies.

The active pharmaceutical ingredient of Sarclisa, isatuximab, is an IgG1 chimeric monoclonal antibody that targets a specific epitope of the CD38 receptor on plasma cells. It can trigger multiple unique mechanisms of action, including promoting 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 or refractory multiple myeloma (R/R MM). Currently, Sanofi is also evaluating isatuximab for the treatment of other hematologic malignancies.Tumorand the potential for solid tumors.

In March 2020, Sarclisa received U.S.FDAApproved in combination with pomalidomide and dexamethasone (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. In early June 2020, the Sarclisa plus pom-dex regimen also received approval from the European Commission (EC).

Sarclisa is 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 market launch.

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. MM is the second most common hematologic malignancyTumorGlobally, the annual number of new cases exceeds 1.38 million. For most patients, multiple myeloma (MM) remains incurable, resulting in a significant unmet medical need in this field. (Bioon.com)

Original source: CHMP recommendsapproval of Sarclisa? (isatuximab) in combination with carfilzomib and dexamethasone for the treatment of relapsed multiple myeloma