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IMBRUVICA gains ninth FDA approval
NORTH CHICAGO, Ill.—AbbVie announced today that the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA (ibrutinib) plus rituximab (Rituxan) for the treatment of adult patients with Waldenström’s macroglobulinemia (WM), a rare and incurable type of non-Hodgkin’s lymphoma (NHL). With this approval, the IMBRUVICA prescribing information now includes combination use with rituximab, representing the first and only chemotherapy-free combination treatment specifically indicated for the disease.
First approved as a single agent therapy for WM in January 2015, IMBRUVICA is a first-in-class, oral, once-daily therapy that mainly works by blocking a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells as well as other serious, debilitating conditions. IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably. IMBRUVICA was jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
IMBRUVICA is FDA-approved for chronic lymphocytic leukemia, small lymphocytic lymphoma and Waldenström’s macroglobulinemia, along with previously-treated mantle cell lymphoma, previously-treated marginal zone lymphoma and previously-treated chronic graft-versus-host disease (cGVHD).
“We are pleased to have IMBRUVICA approved, both as a single agent and combination therapy with rituximab, to provide an additional efficacious treatment option for people living with Waldenström’s macroglobulinemia,” said Thorsten Graef, M.D., Ph.D., Head of Clinical Development at Pharmacyclics LLC, an AbbVie company. “We are proud of our robust clinical development program, and this new approval reflects our continuous commitment to exploring the full potential of IMBRUVICA’s mechanism of action for treating patients with diseases that have great unmet medical need.”
WM is a rare, slow-growing and incurable form of NHL with limited treatment options. WM typically affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen also may be affected. In the U.S., there are about 2,800 new cases of WM each year.
This new FDA approval is supported by data from the Phase 3 iNNOVATE (PCYC-1127) trial evaluating IMBRUVICA in combination with rituximab, versus rituximab alone, in 150 patients with previously untreated and relapsed/refractory WM. Patients were randomized to receive intravenous rituximab 375 mg/m2 once weekly for four consecutive weeks, followed by a second four-weekly rituximab course following a three-month interval. All patients received either ibrutinib 420 mg or placebo once daily continuously until criteria for permanent discontinuation were met. The primary endpoint was progression-free survival, with secondary endpoints including overall response rate, hematological improvement measured by hemoglobin, time-to-next treatment, overall survival, and number of participants with adverse events as a measure of safety and tolerability within each treatment arm.
At a median follow up of 26.5 months, the study demonstrated a significant improvement in progression-free survival (PFS) with IMBRUVICA plus rituximab compared to rituximab alone (30-month PFS rates were 82 percent versus 28 percent, respectively). Patients taking IMBRUVICA plus rituximab also experienced an 80 percent reduction in relative risk of disease progression or death than those only treated with rituximab (hazard ratio, 0.20; confidence interval: 0.11-0.38, P<0.0001). These data were recently presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting and simultaneously published in The New England Journal of Medicine.
“Ibrutinib has significantly advanced the treatment of Waldenström’s macroglobulinemia. The approval of ibrutinib and rituximab has added a new option for many Waldenström’s patients,” noted Steven P. Treon, M.D., Ph.D., Director of the Bing Center for Waldenström’s Macroglobulinemia at the Dana-Farber Cancer Institute, Associate Professor at Harvard Medical School, and lead investigator of the IMBRUVICA Phase 2 clinical trial which served as the basis for its January 2015 FDA approval.
The most common adverse reactions (occurring in 20% or more of patients) of all Grades in patients treated with IMBRUVICA plus rituximab in the iNNOVATE study were bruising (37%), musculoskeletal pain (35%), hemorrhage (32%), diarrhea (28%), rash (24%), arthralgia (24%), nausea (21%), and hypertension (20%).
“The iNNOVATE study demonstrated persuasive clinical evidence supporting the efficacy of IMBRUVICA plus rituximab in Waldenström’s macroglobulinemia,” pointed out Dr. Meletios A. Dimopoulos, Professor and Chairman of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and lead iNNOVATE study investigator. “This approval is a significant milestone for the WM community who have limited treatment options.”