First Chemotherapy-Free Combination Therapy for Leukemia Approved: Ibrutinib Plus Obinutuzumab Achieves 89% Overall Response Rate

Janssen Pharmaceuticals, a Johnson & Johnson company, announced today that the United StatesFDAApproval of IMBRUVICA® (ibrutinib) in combination with obinutuzumab for chronic lymphocyticLeukemia/For previously untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), CLL/SLL is the most common form of leukemia in adults. This is the first chemotherapy-free combination therapy approved for previously untreated patients with CLL/SLL, marking the 10th approval for IMBRUVICA since its initial U.S. approval in November 2013.FDAApproved. This approval expands the labeling of IMBRUVICA for first-line treatment of CLL/SLL beyond its use as monotherapy to include combination therapy with obinutuzumab.

IMBRUVICA is a Bruton’s tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Janssen and Pharmacyclics, an AbbVie company. Its mechanism of action differs from that of chemotherapy, as it blocks the BTK protein. BTK sends critical signals that direct B cells to mature and produce antibodies. BTK signaling is required for the proliferation and spread of certain cancer cells. By inhibiting BTK, IMBRUVICA displaces abnormal B cells from their supportive microenvironment in lymph nodes, bone marrow, and other organs.

This approval was based on the results of the Phase 3 iLLUMINATE study (PCYC-1130). With a median follow-up of 31 months, IMBRUVICA in combination with obinutuzumab demonstrated a significant improvement in progression-free survival (PFS) as assessed by an Independent Review Committee (IRC), with a 77% reduction in the risk of progression or death, compared to chlorambucil in combination with obinutuzumab (median not evaluable [NE] vs. 19 months; hazard ratio [HR] 0.23; 95% confidence interval [CI]: 0.15–0.37; P < 0.0001). In patients with high-risk disease (deletion 17p/TP53 mutation, deletion 11q, or unmutated IGHV) treated with IMBRUVICA in combination with obinutuzumab, the risk of progression or death was reduced by 85% (HR 0.15; 95% CI: 0.09–0.27). The overall response rate (ORR) as assessed by the IRC was 89% in the IMBRUVICA plus obinutuzumab group, compared with 73% in the chlorambucil plus obinutuzumab group. These data were recently presented at the 2018 American Society of Hematology (ASH) Annual Meeting.Conferenceoral presentation, simultaneously published in The LancetTumorJournal of Learning.”

“This label update is based on the established efficacy and safety of IMBRUVICA as a monotherapy or in combination with other therapies in the first-line treatment of patients with CLL/SLL,” said Dr. Craig Tendler, Vice President of Clinical Development and Global Medical Affairs at Janssen Research & Development. “This milestone represents our continued commitment to developing non-chemotherapy regimens based on IMBRUVICA to address the clinical treatment needs of patients with CLL/SLL.”

FDAThe IMBRUVICA label was also updated to include additional long-term efficacy data supporting its use as monotherapy for CLL/SLL, based on approximately five years of follow-up from the international Phase 3 RESONATE™ (PCYC-1112) and RESONATE™-2 (PCYC-1115, PCYC-1116) studies.

Warnings and precautions include bleeding, infection, cytopenia, and arrhythmia.Hypertension, Second Primary Malignant Neoplasms,TumorTumor lysis syndrome and embryotoxicity. Among patients treated with IMBRUVICA in combination with obinutuzumab in the ILLUMINATE study, the most commonAdverse Reactions(Occurring in ≥20% of patients) neutropenia (48%), thrombocytopenia (36%), rash (36%), diarrhea (34%), musculoskeletal pain (33%), bruising (32%), cough (27%), infusion-related reactions (25%), hemorrhage (25%), and arthralgia (22%).

The recommended dosage of IMBRUVICA for the treatment of CLL/SLL is 420 mg orally once daily until disease progression or unacceptable toxicity occurs, whether administered as a monotherapy or in combination with obinutuzumab or bendamustine plus rituximab (BR). When IMBRUVICA is administered in combination with rituximab or obinutuzumab, physicians should consider administering IMBRUVICA prior to rituximab or obinutuzumab on days when both agents are given.

Currently, IMBRUVICA has been approved in more than 90 countries worldwide, and to date, the approved indications have treated over 135,000 patients globally. IMBRUVICA was first approved in the United States in November 2013.FDAApproved for use in six disease areas, including five hematologic malignancies: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p), small lymphocytic lymphoma (SLL) with or without del17p, Waldenström’s macroglobulinemia (WM), previously treated mantle cell lymphoma (MCL), and previously treated marginal zone lymphoma (MZL) in patients who require systemic therapy and have received at least one prior anti-CD20-based regimen; as well as in patients with previously treated chronic graft-versus-host disease (cGVHD) following failure of one or more systemic therapies.

IMBRUVICA is the first and only FDA-approved drug for WM, MZL, and cGVHD. IMBRUVICA has beenFDAGranted four Breakthrough Therapy Designations, and it is one of the first drugs to receive U.S. approval through the Breakthrough Therapy Designation pathway. IMBRUVICA’s robust clinicalTumorThe development plan includes more than 150 items.Clinical TrialStudies on IMBRUVICA as monotherapy, and in combination with medications for severe blood cancers and other serious conditions. (Bio ValleyBioon.com）