Sanofi's CD38-Targeting Antibody Sarclisa Receives Second FDA Approval in Combination Therapy for Relapsed or Refractory Multiple Myeloma
Apr 05, 2021 17:18
CST Updated
17:18
Sanofi
Pharmaceutical R&D Developer
FDA
U.S. Food and Drug Administration
April 05, 2021 News /BioValleyBIOON/ -- Sanofi recently announced that the U.S. Food and Drug Administration (FDA) has approved the CD38-targeted antibody drug Sarclisa (isatuximab) in combination with carfilzomib (Kyprolis®) and dexamethasone (Kd regimen) for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have previously received 1–3 lines of therapy.
It is worth mentioning that this is the United StatesFDASecond approval for Sarclisa in combination with standard-of-care backbone therapy. Previously, the agency had approved Sarclisa in combination with pomalidomide and dexamethasone (pom-dex) for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
This latest approval is based on the Phase III IKEMAClinical Trialresults. The data showed that, in adult patients with relapsed/refractory multiple myeloma (RRMM) who had received 1–3 prior therapies, the Sarclisa + carfilzomib + dexamethasone (S-Kd) regimen significantly reduced the risk of disease progression or death by 47% compared with the standard-of-care carfilzomib + dexamethasone (Kd) regimen. Although the median progression-free survival (PFS) for the S-Kd treatment group had not been reached, consistent improvements in PFS were observed across all subgroups. Furthermore, compared with the Kd regimen, the S-Kd regimen also demonstrated clinically meaningful deep responses (minimal residual disease [MRD] negativity rate: 29.6% vs. 13%).
Dr. Thomas G. Martin, Associate Director of the Myeloma Program at the University of California, San Francisco and Professor of Medicine, stated: “In the Phase 3 IKEMA study, adding Sarclisa to carfilzomib and dexamethasone reduced the risk of disease progression or death by 45%. This approval represents a significant advance for patients with relapsed disease and reinforces the potential of Sarclisa to become the standard of care for relapsed or refractory multiple myeloma.”
SanofiTumorPeter C. Adamson, M.D., Global Head of Pediatric Innovation Development, stated, “The treatment of patients with relapsed or refractory multiple myeloma remains challenging, and unfortunately, those who experience multiple relapses have a poor prognosis. With this approval, Sarclisa is now included in two standard treatment regimens for the early relapse of multiple myeloma. Today’s milestone further supports our ambition to make Sarclisa the preferred anti-CD38 therapy for patients with relapsed or refractory multiple myeloma.”
Mechanism of Action of Isatuximab (Image source: aacrjournals.org)
IKEMA (NCT03275285) is a randomized, multicenter, open-label Phase IIIClinical TrialsA total of 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 two weeks; 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), rate of very good partial response or better (≥VGPR), minimal residual disease (MRD), complete response rate (CR), overall survival (OS), and safety.
The results demonstrated that the study met its primary endpoint: compared with the Kd group (n=123), the S-Kd group (n=179) showed a 45% reduction in the risk of disease progression or death (HR=0.548, 99% CI: 0.366–0.822, p=0.0032) and significantly prolonged progression-free survival (median PFS: not reached vs. 19.15 months). Compared with Kd, the S-Kd regimen demonstrated consistent treatment effects across multiple subgroups. Regarding secondary endpoints, there was no statistically significant difference in overall response rate (ORR) between the S-Kd and Kd groups (86.6% vs. 82.9%; p=0.3859). 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 CR 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 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 TrialsThe safety profile of Sarclisa observed in the study was consistent with previous findings, and no new safety signals were identified.
Multiple myeloma (MM) is the second most common hematologic cancer, with new cases annually worldwideDiagnosisThe number of cases exceeds 138,000. In Europe, there are 39,000 new diagnoses annually; in the United States, there are 32,000 new diagnoses 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 eventually experience relapse and become refractory 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 triggers multiple unique mechanisms of action, including the induction 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-based therapies in MM and other malignancies. Isatuximab has been granted orphan drug designation for the treatment of relapsed or refractory multiple myeloma (R/R MM) in both the United States and the European Union. Currently, Sanofi is also evaluating isatuximab for the treatment of other hematologic malignancies.Tumorand the potential in 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. With indications spanning first- to fourth-line treatment, Darzalex has become a cornerstone of clinical practice, achieving global sales of $4.19 billion in 2020, a 39.8% increase from the previous year. 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 relapsed/refractory multiple myeloma (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, indicating a significant unmet medical need in this field. (Bioon.com)