HORSHAM, Pa., August 27, 2018 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) approval of Imbruvica (ibrutinib) in combination with rituximab for the treatment of Waldenström’s macroglobulinemia (WM), a rare blood cancer.[1] As a first-in-class Bruton's tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company, Imbruvica has achieved another milestone with this approval—it expands the drug’s label in WM from its existing monotherapy indication to include combination use with rituximab, marking the first FDA-approved non-chemotherapy combination option for WM treatment. Notably, Imbruvica first received FDA approval for WM as a monotherapy in January 2015 via the Breakthrough Therapy Designation pathway, becoming the first FDA-approved therapy for the disease, and this expanded label is the ninth FDA approval for Imbruvica since 2013.
Clinical Trial Basis: Phase 3 iNNOVATE Study
The FDA’s approval of Imbruvica plus rituximab for WM is grounded in data from the iNNOVATE study (PCYC-1127), a randomized, double-blind, placebo-controlled Phase 3 trial—the largest of its kind evaluating a non-chemotherapy combination in WM patients. The study enrolled 150 patients with either relapsed/refractory (r/r) or previously untreated WM, comparing the efficacy of Imbruvica plus rituximab versus placebo plus rituximab. At a median follow-up of 26.5 months, the Imbruvica combination arm showed a significant improvement in the Independent Review Committee (IRC)-assessed primary endpoint of progression-free survival (PFS): 30-month PFS rates were 82% in the Imbruvica plus rituximab group, compared to just 28% in the placebo plus rituximab group. Patients receiving the Imbruvica combination also experienced an 80% reduction in the relative risk of disease progression or death (hazard ratio=0.20; confidence interval, 0.11-0.38, p<0.0001). These significant findings were presented in an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, selected for Best of ASCO 2018 Meetings, and simultaneously published in The New England Journal of Medicine.
Expert Perspectives on the Combination Therapy
Dr. Lia Palomba, a hematologist-oncologist at Memorial Sloan-Kettering Cancer Center, New York, and an iNNOVATE study investigator, emphasized the significance of the approval: “The combination of Imbruvica and rituximab provides health care professionals with a new treatment option for patients living with this serious blood cancer. Before Imbruvica, there were no FDA-approved treatment options for patients with Waldenström’s macroglobulinemia, a disease first acknowledged nearly 75 years ago. Today, Imbruvica continues to provide an important therapeutic approach in the treatment of this complex disease.”
Meletios A. Dimopoulos, M.D., Professor and Chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and lead investigator of the iNNOVATE study, added: “Results from iNNOVATE showed significant improvement in progression-free survival at 30 months and demonstrated the superiority of Imbruvica plus rituximab over rituximab monotherapy in Waldenström's macroglobulinemia. Based on these results, Imbruvica in combination with rituximab may be considered as a first- and second-line option for appropriate people diagnosed and living with WM.”
Janssen’s Commitment to WM Patients
Andree Amelsberg, M.D., Vice President of Oncology Medical Affairs at Janssen Scientific Affairs, LLC, commented on the milestone: “The clinical data generated for Imbruvica plus rituximab in the treatment of Waldenström’s macroglobulinemia offers physicians evidence to consider this combination regimen for newly-diagnosed patients. Today’s approval represents an important milestone for people living with this rare and incurable blood cancer who have limited FDA-approved treatment options. We remain dedicated to a comprehensive clinical development program to explore the full potential of Imbruvica, including in combination with other therapies.”
