The U.S. Food and Drug Administration has expanded the approved use of Imbruvica (ibrutinib) for the treatment of patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion). Having the mutation has been found to be associated with poor responses to standard treatments for CLL, and Imbruvica received a breakthrough therapy designation for this recently expanded use.
The breakthrough therapy designation, enacted as part of the FDA's 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies.
"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 news 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 FDA also approved new labeling for Imbruvica to indicate that the drug's clinical benefit in treating CLL has been verified. The drug had received accelerated approval for the treatment of CLL earlier this year based on its effect on overall response rate (OT 3/10/14 issue). New clinical trial results examining progression-free and overall survival have confirmed the drug's clinical benefit.
Also approved by the FDA for the treatment of CLL in the past year are: Gazyva (obinutuzumab)(OT 12/10/13 issue), Arzerra (ofatumumab)(OT 5/10/14 issue), and Zydelig (idelalisib)(http://bit.ly/1so9d3C).
The latest actions for Imbruvica are based on a clinical study of 391 previously treated patients, 127 of whom had CLL with the 17p deletion. The patients were randomly assigned to receive Imbruvica or Arzerra until disease progression or side effects became intolerable. The trial was stopped early for efficacy after a pre-planned interim analysis showed a 78 percent reduction in the risk of disease progression or death, as well as a 57 percent reduction in the risk of death for patients treated with Imbruvica.
Of the patients with the 17p deletion, those receiving Imbruvica had a 75 percent reduction in risk of disease progression or death.
The most common side effects observed in the trial were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, upper respiratory tract infection, rash, nausea, and pyrexia.
The drug's new use was approved more than two months ahead of its prescription drug user fee goal date (which was October 7, 2014). The FDA reviewed Imbruvica's application for this new use under the agency's priority review program, which provides for an expedited review of drugs that are intended to treat a serious disease or condition and, if approved, would offer significant improvement compared to marketed products.
Imbruvica is co-marketed by Pharmacyclics and Janssen Biotech.