On July 23, 2014, the U.S. Food and Drug Administration (FDA) approved idelalisib (Zydelig tablets, GileadSciences, Inc.) for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

FDA also granted accelerated approval to idelalisib for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) or relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies.

The approval for CLL was based on the results of an international, multi-center, randomized (1:1), placebo-controlled trial of 220 patients comparing idelalisib 150 mg twice daily in combination with rituximab to placebo in combination with rituximab. Rituximab was administered in 8 doses (first dose at 375 mg/m2, subsequent doses at 500 mg/m2) every 2 weeks for 4 infusions, then every 4 weeks for 4 infusions.

Progression-free survival (PFS) assessed by blinded independent review committee (IRC) was the primary efficacy endpoint. The trial was stopped early based on an interim analysis; median duration of exposure to idelalisib was 5.0 months. Median PFS was not reached (95% CI 10.7, NR) in the idelalisib plus rituximab arm and was 5.5 months (95% CI 3.8, 7.1) in the placebo plus rituximab arm [HR 0.18 (95% CI: 0.10, 0.32); p < 0.0001].

Accelerated approval for FL and SLL was based on the results of a multi-center, single arm, open-label trial enrolling 123 patients with relapsed indolent non-Hodgkin lymphomas who were started on idelalisib 150 mg twice daily. The primary efficacy endpoint was overall response rate (ORR) as assessed by an IRC. In patients with FL, the ORR was 54% (95% CI: 42, 66), and the median response duration was not evaluable. In patients with SLL, the ORR was 58% (95% CI: 37, 77), and the median response duration was 11.9 months.

Idelalisib is being approved with a Boxed Warning alerting patients and healthcare professionals of the following fatal and serious adverse reactions: hepatotoxicity, severe diarrhea or colitis, pneumonitis, and intestinal perforation. The most common adverse reactions (incidence greater than or equal to 20%) are diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash. The most common lab abnormalities (incidence greater than or equal to 30%) are neutropenia, hypertriglyceridemia, hyperglycemia, ALT elevations, and AST elevations.

The recommended dose and schedule for idelalisib is 150 mg orally twice daily for patients with FL and SLL and in combination with rituximab for patients with CLL.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206545lbl.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).


Page Last Updated: 09/15/2015
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