HORSHAM, PA, January 28, 2019 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® (ibrutinib) in combination with obinutuzumab for treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the most common form of leukemia in adults¹. This marks the first FDA-approved non-chemotherapy combination regimen for treatment-naïve CLL/SLL patients and the tenth FDA approval for IMBRUVICA® since its initial U.S. launch in November 2013. This approval expands the IMBRUVICA® label for frontline CLL/SLL treatment, adding combination use with obinutuzumab to its existing indication as a monotherapy. IMBRUVICA®, a Bruton's tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.
Expert Perspective: Dr. Carol Moreno
"In just a few years, IMBRUVICA has become a cornerstone of treatment for chronic lymphocytic leukemia," said Carol Moreno, M.D., Ph.D., Consultant Hematologist, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, and lead investigator of the iLLUMINATE study. "IMBRUVICA as a monotherapy, and now in combination with obinutuzumab, provides CLL patients with an alternative to frontline chemoimmunotherapy."
Clinical Trial Basis: Phase 3 iLLUMINATE Study
The approval is based on results from the Phase 3 iLLUMINATE study (PCYC-1130). At a median follow-up of 31 months, IMBRUVICA® plus obinutuzumab demonstrated a significant improvement in progression-free survival (PFS) as assessed by an Independent Review Committee (IRC) compared to chlorambucil plus obinutuzumab (median not reached vs. 19 months; HR 0.23; 95% CI: 0.15-0.37; P<0.0001), representing a 77 percent reduction in the risk of disease progression or death. For patients with high-risk disease (17p deletion/TP53 mutation, 11q deletion, or unmutated IGHV), the combination reduced the risk of progression or death by 85 percent (HR 0.15; 95% CI: 0.09-0.27). The overall response rate (ORR) per IRC was 89 percent in the IMBRUVICA® plus obinutuzumab arm versus 73 percent in the chlorambucil plus obinutuzumab arm. These data were recently presented during an oral session at the 2018 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The Lancet Oncology.
Janssen’s Perspective on the Approval
"This label update builds upon the established efficacy and safety of IMBRUVICA as a monotherapy or in combination with other therapies for the frontline treatment of patients with CLL/SLL," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. "This milestone reflects our ongoing commitment to developing IMBRUVICA-based non-chemotherapy regimens to meet the clinical needs of patients with CLL/SLL."
Additional Label Update: Long-Term Monotherapy Efficacy Data
The FDA also updated the IMBRUVICA® label to include additional long-term efficacy data supporting its use as a monotherapy in CLL/SLL, based on approximately five years of follow-up from the Phase 3 RESONATE™ (PCYC-1112) and RESONATE™-2 (PCYC-1115, PCYC-1116) international studies.
Warnings, Precautions and Adverse Reactions
Warnings and precautions include hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. In the iLLUMINATE study, the most common adverse reactions of all grades (occurring in 20 percent or more of patients) treated with IMBRUVICA® plus obinutuzumab were neutropenia (48%), thrombocytopenia (36%), rash (36%), diarrhea (34%), musculoskeletal pain (33%), bruising (32%), cough (27%), infusion-related reactions (25%), hemorrhage (25%), and arthralgia (22%).
