On November 16, 2015, the U.S. Food and Drug Administration granted accelerated approval to daratumumab injection (DARZALEX, Janssen Biotech, Inc.), administered as a single agent for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
Daratumumab is the first monoclonal antibody approved for the treatment of multiple myeloma. The approval was based on a multi-center, open-label study evaluating response rates in 106 patients with relapsed or refractory multiple myeloma treated with daratumumab monotherapy. The objective response rate was 29% (95% CI: 21-39%) with a median response duration of 7.4 months (range: 1.2 to 13.1+ months).
Safety data was evaluated in 156 patients who received the proposed dose and schedule of daratumumab. The most frequently reported adverse reactions (incidence greater than or equal to 20%) were infusion reactions, fatigue, nausea, back pain, pyrexia, cough, and upper respiratory tract infection. Pre-medication and post-infusion medications are recommended to prevent infusion reactions. The most common laboratory abnormalities were lymphopenia, neutropenia, anemia, and thrombocytopenia.
Daratumumab interferes with blood bank crossmatching, specifically with Indirect Antiglobulin Tests. If blood transfusion is necessary, inform the blood bank that a patient has received daratumumab.
As a condition of this accelerated approval, Janssen is required to conduct a multicenter, randomized trial establishing the superiority of daratumumab over standard therapy to verify and describe the clinical benefit of daratumumab. Janssen has several ongoing multicenter, randomized trials in patients with multiple myeloma with a primary endpoint of progression-free survival.
The recommended dose and schedule for daratumumab is 16 mg/kg once every week for 8 weeks, then once every 2 weeks for 16 weeks, then once every 4 weeks until disease progression.
Daratumumab is being approved prior to the Prescription Drug User Fee Act (PDUFA) goal date of March 9, 2016. This application was granted Priority Review, Breakthrough Therapy Designation and Accelerated Approval. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:
Full prescribing information is available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).