On November 21, 2016, the U.S. Food and Drug Administration approved daratumumab (DARZALEX, Janssen Biotech, Inc.) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.
Daratumumab was previously granted accelerated approval in November 2015 as monotherapy for 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.
The current approval was based on two randomized, open-label trials in which daratumumab was added to standard therapies. The POLLUX trial (also known as MMY3003), demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The estimated median PFS had not been reached in the daratumumab arm and was 18.4 months in the control arm (HR=0.37; 95% CI: 0.27, 0.52; p<0.0001), representing a 63% reduction in the risk of disease progression or death in patients treated with daratumumab.
Similar results were observed in the CASTOR trial (also known as MMY3004), which compared the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone. The estimated median PFS was not reached in the daratumumab arm and was 7.2 months in the control arm (HR=0.39; 95% CI: 0.28, 0.53; p<0.0001), representing a 61% reduction in the risk of disease progression or death for patients treated with daratumumab.
The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3003 were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough and dyspnea. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3004 were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, peripheral sensory Neutropenia and thrombocytopenia have been added to the Warnings and Precautions of the DARZALEX label.
The recommended dose of daratumumab is 16 mg/kg intravenously (calculated on actual body weight).
FDA granted daratumumab breakthrough therapy and orphan drug designation, as well as priority review. The current approval was granted three months prior to the PDUFA date of February 17, 2017. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf
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).
US Food and Drug Administration. Daratumumab (darzalex). Updated November 22, 2016.