- U.S. Food and Drug Administration (FDA) (http://dev-voice.ons.org/topic/us-food-and-drug-administration-fda)
- Oncology Drug Research (http://dev-voice.ons.org/topic/oncology-drug-research)
- Multiple Myeloma (http://dev-voice.ons.org/topic/multiple-myeloma)
- Clinical Practice (http://dev-voice.ons.org/topic/clinical-practice)
FDA Approves Isatuximab-Irfc for Multiple Myeloma
On March 31, 2021, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-isatuximab-irfc-multiple-myeloma) isatuximab-irfc (Sarclisa®) in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
Efficacy and safety were evaluated in a multicenter, multinational, randomized, open-label, two-arm, phase III trial (IKEMA; NCT03275285) of 302 patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. Patients were randomized 3:2 to receive either isatuximab-irfc with carfilzomib and dexamethasone (Isa-Kd) or carfilzomib and dexamethasone (Kd).
The main efficacy outcome measurement was progression-free survival (PFS) assessed by an independent response committee based on central laboratory data for M-protein and central radiologic imaging review using international myeloma working group criteria. Median PFS was not reached in the Isa-Kd arm and was 20.27 months (95% CI = 15.77, not reached) in the Kd arm (hazard ratio = 0.548; 95% CI = 0.366, 0.822; p = 0.0032), representing a 45% reduction in the risk of disease progression or death in patients treated with Isa-Kd compared to those treated with Kd.
The most common adverse reactions (≥ 20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥ 80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
The recommended isatuximab-irfc dose with carfilzomib and dexamethasone is 10 mg/kg via IV infusion every week for four weeks followed by every two weeks until patients experience disease progression or unacceptable toxicity.
The review used Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application three months ahead of its goal date.
FDA granted the application orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).