Silver Spring, MD (Press Release) – On November 20, 2015, the U.S. Food and Drug Admin­istra­tion approved ixazomib (NINLARO, Millennium Pharma­ceu­ticals, Inc., a wholly owned sub­sid­i­ary of Takeda Pharma­ceu­ti­cal Company Limited) in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy. Ixazomib is the first approved oral pro­te­a­some inhibitor.

The approval was based on an im­prove­ment in pro­gres­sion- free survival (PFS) in a multi­center, ran­dom­ized, double-blind, placebo-controlled trial enrolling 722 patients with multiple myeloma who had received 1 to 3 prior lines of ther­apy. Patients were ran­dom­ized in a 1:1 ratio to either the com­bi­na­tion of ixazomib, lena­lido­mide and dexa­meth­a­sone (n=360) or the com­bi­na­tion of placebo, lena­lido­mide and dexa­meth­a­sone (n=362). Patients con­tinued treat­ment until disease pro­gres­sion or unacceptable toxicity.

The trial showed a statistically sig­nif­i­cant im­prove­ment in PFS. The median PFS on the com­bi­na­tion arm of ixazomib, lena­lido­mide and dexa­meth­a­sone was 20.6 months (95% CI: 17.0, NE) compared to a median PFS of 14.7 months (95% CI: 12.9, 17.6) on the com­bi­na­tion arm of placebo, lena­lido­mide and dexa­metha­sone (PFS HR 0.74, 95% CI: 0.59, 0.94; p value=0.012).

The more common (>20%) adverse reac­tions asso­ci­ated with an in­­creased rate on the ixazomib com­bi­na­tion arm compared to the placebo combi­na­tion arm were diarrhea, con­sti­pa­tion, thrombo­cyto­penia, periph­eral neu­rop­athy, nausea, periph­eral edema, vomiting, and back pain.

The recommended starting dose of ixazomib is 4 mg orally on days 1, 8, and 15 of a 28 day cycle in com­bi­na­tion with lena­lido­mide 25 mg daily on days 1 through 21 and dexa­meth­a­sone 40 mg on days 1, 8, 15, and 22 of a 28 day treat­ment cycle.

This appli­ca­tion was approved before its Prescription Drug User Fee Act (PDUFA) date of March 10, 2016. The appli­ca­tion was granted Priority Review. A description of expedited review 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/2015/208462lbl.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: The Food and Drug Admin­istra­tion.