Ibrutinib is now approved for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy, the Food and Drug Administration announced Nov. 13.
The once-daily, oral therapy, marketed as Imbruvica, is the second drug to receive FDA approval under the breakthrough therapy designation established to speed the development and review of treatments for serious or life-threatening diseases.
"Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases," Dr. Richard Pazdur, director of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in a statement.
Dr. Richard Pazdur
Mantle cell lymphoma is an orphan disease, with only about 2,900 new cases of MCL diagnosed each year. MCL comprises only about 6% of all non-Hodgkin’s lymphoma cases in the United States.
Ibrutinib’s approval comes a little more than 4 months after the new drug application was filed in June 2013 and is based on a phase II study reporting an investigator-assessed overall response rate of 66% at a daily dose of 560 mg ibrutinib in 111 patients with relapsed or refractory MCL after a median of three prior therapies. The median duration of response was 17.5 months. An improvement in survival and disease-related symptoms has not been established.
Ibrutinib works by blocking Bruton’s tyrosine kinase, a mediator of the B-cell receptor signaling pathway that has been shown in nonclinical studies to inhibit malignant B-cell survival.
The FDA also granted ibrutinib priority review and orphan-product designation, because the drug demonstrated "the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease," according to the FDA statement.
Ibrutinib is the third drug approved to treat MCL. In June 2013, the FDA approved the oral thalidomide analogue lenalidomide (Revlimid) for the treatment of MCL that had relapsed or progressed after two prior therapies including bortezomib (Velcade), a subcutaneous therapy that has been available for MCL since 2006.
"It is gratifying to see an early example of the new breakthrough therapy designation pathway meeting its intention – getting promising treatments to patients who are waiting for new options," Dr. Ellen V. Sigal, chairperson and founder of the Washington-based Friends of Cancer Research advocacy organization, said in a statement issued by Janssen Biotech, which is comarketing the drug with Pharmacyclics.
The two companies are expected to continue with phase III studies of ibrutinib and have also submitted the drug to the FDA for the treatment of previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma.
In the pivotal MCL trial, the most common treatment-related adverse events with single-agent ibrutinib were mild or moderate diarrhea, fatigue, and nausea (N. Engl. J. Med. 2013;369:507-16). Grade 3 or higher hematologic events were neutropenia (16%), thrombocytopenia (11%), and anemia (10%).