On January 29, 2015 Pharmacyclics reported that the U.S. Food and Drug Administration (FDA) has granted single-agent IMBRUVICA (ibrutinib) regular (full) approval in all lines of therapy as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM), a rare, indolent type of B-cell lymphoma (Press release Pharmacyclics, JAN 29, 2015, View Source [SID:1234501415]). This is the fourth indication for IMBRUVICA, an oral therapy, which received FDA Breakthrough Therapy Designation for this indication in February 2013. IMBRUVICA is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

“Because there has never been an FDA-approved treatment for Waldenstrom’s macroglobulinemia since it was first identified over 70 years ago, doctors had to rely on therapies borrowed from similar cancers to treat these patients,” Steven P. Treon, M.D., Ph.D., Director of the Bing Center for Waldenstrom’s Macroglobulinemia at the Dana-Farber Cancer Institute and Associate Professor at Harvard Medical School, Boston, Mass., and lead investigator of the WM trial data submitted to the FDA for this approval. “I am truly grateful to the FDA for recognizing this need and for approving IMBRUVICA, and I thank those scientists whose hard work and dedication helped discover the genetic cause of this disease and identified ibrutinib as a targeted therapy, and those clinicians at several leading medical centers who diligently enrolled the clinical trial showing that IMBRUVICA is a safe and highly effective therapy for patients with Waldenstrom’s macroglobulinemia.”

“The FDA’s approval of IMBRUVICA for Waldenstrom’s macroglobulinemia marks a significant milestone for patients living with this rare disease and has the potential to positively impact the lives of a number of patients,” said Carl Harrington, President of the International Waldenstrom’s Macroglobulinemia Foundation, who also is a patient living with WM.
The approval is based on results from a multi-center, Phase II study that evaluated the efficacy and tolerability of IMBRUVICA in 63 patients with previously treated WM. In this study, IMBRUVICA demonstrated a response rate of 62% according to an Independent Review Committee. Very good partial responses (VGPR) of 11% and partial responses (PR) of 51% were observed. These responses were maintained and the median duration of response (DOR) has not been reached, with a range of 2.8+ to 18.8+ months.
“IMBRUVICA has demonstrated its effectiveness in patients living with Waldenstrom’s macroglobulinemia who, until now, did not have an FDA-approved standard-of-care therapy,” said Thorsten Graef, M.D., Ph.D., Head of Hematology at Pharmacyclics. “This approval is a proud moment for our Pharmacyclics and Janssen teams and would not have been possible without the dedication and support of our patients, clinical investigators and the FDA’s recognition of IMBRUVICA as a breakthrough therapy for these patients.”

WM (a clinically recognized subset of lymphoplasmacytic lymphoma, or LPL) is a slow-growing and rare blood cancer that most commonly originates from B cells, a type of white blood cell (lymphocyte) that develops in the bone marrow.2 In the United States, approximately 1,000 to 1,500 people are diagnosed each year,3 with the median age at diagnosis being 60 to 70 years of age.4 WM occurs as the result of a malfunction in the healthy lifecycle of a B cell, causing the cell to become malignant and reproduce at an abnormal rate. The malignant B cells produce large amounts of an abnormal type of antibody protein called immunoglobulin M (IgM). Excess IgM causes the blood to thicken and causes many of the symptoms of WM.2
Consistent with the previous label, the most commonly occurring adverse reactions in WM patients treated with IMBRUVICA ( > 20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue. Six percent of patients receiving IMBRUVICA in the WM trial discontinued treatment due to adverse events. Adverse events leading to dose reduction occurred in 11% of patients.
In addition, the warnings and precautions for IMBRUVICA were updated and reflect the most current safety knowledge based on ongoing clinical investigation and commercial use.