FDA expands Imbruvica approval for two CLL indications

The FDA today expanded the approved use of ibrutinib to treat patients with chronic lymphocytic leukemia who have received at least one prior therapy and for patients with chronic lymphocytic leukemia who carry a deletion in chromosome 17.

The FDA also has approved new labeling to reflect that the clinical benefit of ibrutinib (Imbruvica, Pharmacyclics and Janssen Biotech) in treating CLL has been verified.

“We continue to see advances in the availability of therapies to treat chronic lymphocytic leukemia, especially for difficult-to-treat patient populations,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “Imbruvica is the fourth drug approved to treat CLL that received a breakthrough therapy designation, reflecting the promise of the breakthrough therapy designation program and demonstrating the FDA’s commitment to working cooperatively with companies to expedite the development, review and approval of these important new drugs.”

The other three drugs approved to treat CLL that received breakthrough designations include: obinutuzumab (Gazyva, Roche) in November, ofatumumab (Arzerra, GlaxoSmithKline) in April and idelalisib (Zydelig, Gilead) in July.

The FDA expanded ibrutinib’s indication based on results of the phase 3 RESONATE study that included 391 previously treated patients, 127 of whom had CLL with 17p deletion. Patients were randomly assigned to ibrutinib or ofatumumab until disease progression or side effects became intolerable.

The trial was stopped early for efficacy after a pre-planned interim analysis demonstrated ibrutinib-treated patients experienced a 78% reduction in risk for PFS. Results also showed a 57% reduction in OS in participants treated with ibrutinib.

John C. Byrd

Of the 127 patients who had CLL with 17p deletion, those treated with ibrutinib experienced a 75% reduction in risk for disease progression or death.

“Imbruvica demonstrated substantial evidence of its superiority over ofatumumab and significant benefit for previously treated CLL patients, while maintaining a favorable safety profile. This FDA approval for Imbruvica is a major step toward chemo-free treatment in CLL,” John C. Byrd, MD, professor of medicine and medicinal chemistry at the Ohio State Comprehensive Cancer Center and lead investigator of the RESONATE trial, said in a press release. “Patients with deletion 17p CLL are at particularly high risk for poor outcomes. Today’s approval of Imbruvica provides these patients with the only FDA-approved treatment, regardless of whether their disease is treatment naïve or previously treated. I continue to be awed by the duration of my patients' responses to Imbruvica and am grateful Imbruvica now is available to a broader group of CLL patients.”

The most frequent adverse events observed in the clinical study were thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, fever and nausea, according to the FDA.