AbbVie/J&J’s Imbruvica Plus Rituximab Demonstrates Significant Overall Survival Benefit in First-Line CLL Treatment, Offering a Chemotherapy-Free Alternative

December 12, 2019 News /BioonBIOON/ -- The 61st Annual Meeting of the American Society of Hematology (ASH 2019) was recently held in Orlando, Florida, USA. ThisMeetingAbbVie and Johnson & Johnson (JNJ) announced that the targeted anticancer drug Imbruvica® (Chinese brand name: Yike®, generic name: ) in combination with rituximab as first-line treatment for chronic lymphocyticLeukemiaLong-Term Results from the Extended Follow-Up of the Phase III E1912 Study (NCT02048813) in Chronic Lymphocytic Leukemia (CLL).

Imbruvica is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor administered orally once daily, jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech, Inc., a Johnson & Johnson company.

The extended follow-up phase of the E1912 study evaluated 354 previously untreated (treatment-naïve), younger (aged ≤70 years) patients with chronic lymphocytic leukemia (CLL) who were randomized to receive either Imbruvica plus rituximab (IR) or chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS).

The results demonstrated that the study met its PFS and OS endpoints. With a median follow-up of 48 months, 73% of patients in the IR regimen group were still receiving Imbruvica treatment, with a median treatment duration of 43 months (range: 0.2–61 months). The median time to disease progression or death after discontinuation of Imbruvica was 23 months. Compared with the FCR regimen group, the IR regimen group showed a sustained and superior PFS benefit (HR=0.39 [95% CI: 0.26–0.57]; p<0.0001). Furthermore, compared with the FCR regimen group, the IR regimen group demonstrated a sustained and superior OS benefit (HR=0.34; 95% CI: 0.15–0.79; p=0.009). Regarding safety, the proportions of patients experiencing grade 3 or higher treatment-emergent adverse events (TEAEs) were 70% and 80% in the IR and FCR regimen groups, respectively (odds ratio [OR]=0.56; 95% CI: 0.34–0.90; p=0.013).

Based on the results of the E1912 study, AbbVie submitted to the U.S. this NovemberFDASubmitted a supplemental New Drug Application (sNDA) for the use of the Imbruvica + rituximab (IR) regimen in younger patients (≤70 years) with chronic lymphocytic leukemia (CLL).）or first-line treatment for small lymphocytic lymphoma (SLL).

Imbruvica is a small-molecule drug administered orally once daily. It exerts its anticancer effects primarily by inhibiting Bruton’s tyrosine kinase (BTK), which is required for the proliferation and metastasis of cancer cells. BTK is a key signaling molecule within the B-cell receptor signaling complex and plays a critical role in the survival and metastasis of malignant B cells, as well as in various other serious debilitating diseases.

Imbruvica can block the signaling pathways that mediate the uncontrolled proliferation and spread of B cells, helping to kill cancer cells and reduce their numbers, thereby delaying the progression of cancer. InClinical Trial, monotherapy and combination therapies for a wide range of hematologic malignanciesTumorDemonstrated robust efficacy.

Since its launch in 2013, Imbruvica has received 10 approvals across a total of six indications, including five B-cell hematologic malignancies and chronic graft-versus-host disease (cGVHD).FDAApproved: Chronic lymphocytic leukemia (CLL) with or without 17p deletion mutation (del17p), small lymphocytic lymphoma (SLL) with or without 17p deletion mutation (del17p), Waldenström macroglobulinemia (WM), previously treated mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) requiring systemic therapy and having received at least one prior anti-CD20 therapy, and chronic graft-versus-host disease (cGVHD) following failure of one or more systemic therapies.

Currently, AbbVie and Johnson & Johnson are advancing a large-scale Imbruvica clinicalTumorDevelopment Project. The industry holds a very optimistic view of the commercial prospects for Imbruvica. In June this year, the pharmaceutical market research firm EvaluatePharma released a report stating that Imbruvica’s global sales in 2018 amounted to $4.454 billion, and with continuous market penetration and an expanding range of indications, global sales are projected to reach $9.514 billion by 2024. (Bioon.com)

Original Source:Extended Follow-up Phase 3 Data Underscore Sustained Efficacy and Safety of IMBRUVICA® (ibrutinib) in the Treatment of Chronic Lymphocytic Leukemia (CLL)