The U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for isatuximab (SAR650984), being developed by French drugmaker Sanofi for the treatment of patients with relapsed/refractory multiple myeloma.
The target action date for the FDA decision is April 30, 2020.
Isatuximab is an investigational monoclonal antibody that targets a specific epitope on the CD38 receptor of a plasma cell.
The BLA is based on positive results from ICARIA-MM (NCT02990338), an open-label pivotal Phase III clinical trial of isatuximab in patients with relapsed/refractory multiple myeloma.
The primary objective of the trial was 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 refractory or relapsed and refractory multiple myeloma (MM).
Participating patients with relapsed/refractory multiple myeloma who received ≥2 prior lines, including lenalidomide and a proteasome inhibitor, refractory to their last therapy were enrolled.
Patients received isatuximab 10 mg/kg IV weekly for first 4 weeks, then every 2 weeks. Both trial arms received approved schedules of pomalidomide and dexamethasone (4mg PO days 1-21; 40mg [20mg if >75 yrs] PO or IV weekly) every 28 days until progression or unacceptable toxicity.
A total of 307 patients (154 receiving isatuximab in combination with pomalidomide; 153 receiving pomalidomide) were randomized. The median age of these patients was 67 (36-86) years of age.
At median follow-up of 11.6 months, the median PFS was 11.5 months for patients receiving isatuximab in combination with pomalidomide vs 6.5 months for patients in the pomalidomide arm (HR 0.596 [95% CI 0.44-0.81], P=0.001.
The ICARIA-MM study was the first positive randomized Phase III trial to evaluate an antibody in combination with pomalidomide and dexamethasone. The results from this trial were presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill. and the 2019 annual meeting of the European Society of Hematology (EHA) in Amsterdam, The Netherlands
Common Hematologic Malignancy
Multiple myeloma is the second most common hematologic malignancy, affecting more than 138,0002 people worldwide. Multiple myeloma results in significant disease burden. Patients with multiple myeloma continue to relapse over time making it a difficult to treat and incurable malignancy.
Isatuximab targets a specific epitope on the CD38 receptor. It is designed to trigger multiple, distinct mechanisms of action that are believed to directly promote programmed tumor cell death (apoptosis) and immunomodulatory activity.
Isatuximab received orphan designation for relapsed/refractory multiple myeloma from both the FDA and the European Medicines Agency (EMA), and in the second quarter of 2019 the EMA accepted for review the Marketing Authorization Application.
Isatuximab is currently being evaluated in multiple ongoing Phase III clinical trials in combination with current standard treatments for people with relapsed/refractory or newly-diagnosed multiple myeloma. It is also under investigation for the treatment of other hematologic malignancies and solid tumors.
Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM) | (NCT02990338)
 Richardson PG, Attal M, Rajkumar SV, San Miguel J, Beksac M, Spicka I, Leleu X, et al. A phase III randomized, open label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Abstract presented on June 2, 2019. J Clin Oncol 37, 2019 (suppl; abstr 8004)
 Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016 Dec;43(6):676-681. doi: 10.1053/j.seminoncol.2016.11.004. Epub 2016 Nov 10. [PubMed][Article]