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U.S. Department of Health and Human Services

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Ibrutinib (IMBRUVICA)

On February 12, 2014, the U. S. Food and Drug Administration granted accelerated approval to ibrutinib (IMBRUVICA, Pharmacyclics, Inc.) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.  Ibrutinib previously received accelerated approval on November 13, 2013 for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy.

 
The approval in CLL was based on the results of a multi-center, single-arm trial of 48 patients with previously treated CLL. The median age was 67 years (range, 37 to 82 years) and 71% were male. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 6.7 years and the median number of prior treatments was 4 (range, 1 to 12 treatments).  Ibrutinib was administered orally at 420 mg once daily until disease progression or unacceptable toxicity.
 
The efficacy results demonstrated a 58.3% overall response rate (95% CI: 43.2, 72.4) as assessed by an independent review committee. No complete responses were observed. The response duration ranged from 5.6 to 24.2+ months; the median was not reached.
 
The safety profile of ibrutinib for patients with previously treated CLL was consistent with observations in the mantle cell lymphoma clinical trial. The most common adverse reactions reported in the CLL clinical trial (occurring in greater than or equal to 20% of patients) were thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, pyrexia, constipation, peripheral edema, arthralgia, nausea, stomatitis, sinusitis, and dizziness.
 
As a condition of this accelerated approval, the FDA required that the sponsor submit results of randomized clinical trial(s.) In January 2014, Pharmacyclics notified FDA of the early stopping of the RESONATE trial by the Data Monitoring Committee (DMC) based on favorable results of a planned interim analysis. RESONATE, a phase 3 clinical trial, randomized patients to either ibrutinib or ofatumumab.  Patients entered on this trial had previously treated CLL or small lymphocytic lymphoma (SLL) and were not considered candidates for treatment with purine analogue-based treatments.  The trial was reported to demonstrate an improvement in progression-free survival and overall survival.  
 
The recommended dose and schedule of ibrutinib for patients with CLL is 420 mg (three 140 mg capsules) taken orally once daily.
 
Full prescribing information is available at: 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203147s000lbl.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).