The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending a change to the terms of the marketing authorization for IMBRUVICA (ibrutinib) in the European Union to indicate the treatment of adult patients with Waldenström's macroglobulinemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.
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 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.. IMBRUVICA is also the first and only FDA-approved treatment for WM in the United States. The CHMP recommendation follows the January 2015 U.S. Food and Drug Administration (FDA) full approval of IMBRUVICA to treat all lines of patients with WM.
WM currently affects approximately 23,000 patients in the G7 countries (United States, France, Germany, Italy, Japan and the United Kingdom).3 The CHMP recommendation was based on a multi-center, Phase II study that evaluated the efficacy and tolerability of IMBRUVICA in 63 patients with previously treated WM. Initial data from the study submitted for review in the EU showed an overall response rate (ORR) of 87.3% after a median duration of treatment of 11.7 months.
Updated results from the study were published on in the April 9, 2015 edition of The New England Journal of Medicine, indicating an ORR of 90.5% after a median duration of treatment of 19.1 months using criteria adopted from the International Workshop on WM. At 24 months, the estimated rate of progression-free survival was 69.1% (95% CI, 53.2 to 80.5), and the estimated rate of overall survival was 95.2% (95% CI, 86.0 to 98.4).
No new safety issues were observed in the clinical trial. The most commonly occurring adverse reactions in WM patients treated with IMBRUVICA (>20%) were neutropenia and thrombocytopenia. Other adverse reactions occurred in <10% of patients (n=5). Six percent of patients receiving IMBRUVICA in the WM trial discontinued treatment due to neutropenia or thrombocytopenia. Of note, IMBRUVICA-related neutropenia and thrombocytopenia were reversible, but required a reduction in dose and/or discontinuation of treatment with IMBRUVICA in three of the four patients who developed these conditions. Overall, IMBRUVICA was well tolerated and there were no unexpected toxicities.
IMBRUVICA is jointly developed and commercialized in the United States by Pharmacyclics and Janssen Biotech, Inc. In Europe, Janssen-Cilag International NV (Janssen) holds the marketing authorization and its affiliates market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world. IMBRUVICA is already approved in Europe to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL) and adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy or in first line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.