Silver Spring, MD (Press Release) – 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).

Source: United States Food and Drug Admin­istra­tion.