Silver Spring, MD (Approval & Safety Notification) – On Sep­tem­ber 26, 2019, the Food and Drug Admin­istra­tion approved dara­tu­mu­mab (DARZALEX, Janssen) for adult patients with multiple myeloma in com­bi­na­tion with bor­tez­o­mib, thalido­mide, and dexa­meth­a­sone in newly diag­nosed patients who are eli­gible for au­tol­o­gous stem cell trans­plant (ASCT).

Efficacy was in­ves­ti­gated in CASSIOPEIA (NCT02541383), an open-label, ran­dom­ized, active-controlled phase 3 study com­par­ing induction and con­sol­i­da­tion treat­ment with dara­tu­mu­mab 16 mg/kg in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone (DVTd) to treat­ment with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone (VTd) in patients with newly diag­nosed multiple myeloma eli­gible for ASCT.

Approval is based on data from CASSIOPEIA, in­clud­ing pro­gres­sion-free survival (PFS), stringent com­plete response (sCR) at 100 days post-ASCT, and CR rate at day 100 post-ASCT. The trial dem­onstrated an im­prove­ment in PFS in the DVTd arm as com­pared to the VTd arm; with a median follow up of 18.8 months, the median PFS had not been reached in either arm. Treatment with DVTd resulted in a reduction in the risk of pro­gres­sion or death by 53% com­pared to VTd alone (HR=0.47; 95% CI: 0.33, 0.67; p<0.0001).The sCR rate at Day 100 post-ASCT was 28.9% in the DVTd arm and 20.3% in the VTd arm.

In patients with newly diag­nosed multiple myeloma who received dara­tu­mu­mab in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone, the most frequent (≥20%) adverse reac­tions were in­fusion reac­tions, periph­eral sensory neu­rop­athy, con­sti­pa­tion, asthenia, nausea, periph­eral edema, neu­tro­penia, thrombo­cyto­penia, pyrexia and paresthesia. Adverse reac­tions that occurred with at least 5% greater frequency in the DVTd arm were in­fusion reac­tions, nausea, neu­tro­penia, thrombo­cyto­penia, lymphopenia and cough. There were no sig­nif­i­cant dif­fer­ences in the number or type of serious adverse events in the two treat­ment arms.

The rec­om­mended dara­tu­mu­mab dose is 16 mg/kg actual body weight.

View full pre­scrib­ing in­for­ma­tion for DARZALEX.

FDA granted this appli­ca­tion priority review. A description of FDA expedited pro­grams is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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 or by calling 1-800-FDA-1088.

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For assistance with single-patient INDs for inves­ti­ga­tional on­col­ogy prod­ucts, health­care professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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Source: Food and Drug Admin­istra­tion.