Janssen Announces European Commission Approval of Imbruvica (Ibrutinib) Plus Rituximab as First-Line Chemotherapy-Free Regimen for Chronic Lymphocytic Leukemia

September 08, 2020 News /BioonBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced that the European Commission (EC) has approved Imbruvica (ibrutinib), in combination with rituximab, for the first-line treatment of chronic lymphocyticLeukemia(CLL) adult patients. This approval is based on the results of the Phase III E1912 study (NCT02048813), which demonstrated that in previously untreated CLL patients aged ≤70 years, the Imbruvica plus rituximab (IR) regimen significantly prolonged progression-free survival (PFS) compared with the chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR).

In April this year, Imbruvica received approval from the U.S. FDA for use in combination with rituximab as a first-line treatment for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This milestone marks the period since its initial approval in 2013,FDAThe 11th approval of Imbruvica across six different disease areas, and the 6th approval for the treatment of CLL, CLL is the most common type of leukemia in the adult population.

Historically, the FCR chemotherapy regimen has been the standard first-line treatment for previously untreated patients with chronic lymphocytic leukemia (CLL).IR is a non-chemotherapy combination regimen that can prolong the duration of disease remission while reducing chemotherapy-related side effects.The IR regimen will provide an important new option for first-line treatment of CLL.

Imbruvica is a first-in-class, once-daily oral Bruton’s tyrosine kinase (BTK) inhibitor, jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech, Inc., a Johnson & Johnson company. To date, Imbruvica has been used to treat more than 200,000 patients worldwide across its approved indications.

The E1912 study evaluated a total of 529 patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). In the study, these patients were randomized into two groups: (1) the IR regimen group (n=354), which received six cycles of Imbruvica plus rituximab, followed by Imbruvica monotherapy until disease progression or unacceptable toxicity; and (2) the FCR regimen group (n=175), which received six cycles of the FCR regimen. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoint was overall survival (OS).

With a median follow-up of 37 months, the IR group demonstrated longer progression-free survival (PFS): the PFS rate was 88% in the IR group versus 75% in the FCR group (HR=0.34, 95% CI: 0.22–0.52, p<0.0001). Furthermore, the IR group showed a significant advantage in overall survival (OS). The primary study results were previously published in the New England Journal of Medicine (NEJM). The 4-year follow-up results, presented at the 2019 American Society of Hematology (ASH) Annual Meeting, confirmed the sustained initial treatment benefit.Median follow-up: 48 months, compared with the FCR regimen group, the IR regimen group demonstrated a sustained superior PFS benefit (HR=0.39 [95% CI: 0.26-0.57], p<0.0001),61% Reduction in Risk of Disease Progression or DeathFurthermore, compared with the FCR regimen group, the IR regimen group demonstrated a sustained superior overall survival (OS) benefit (HR=0.34; 95% CI: 0.15–0.79; p=0.009),66% Reduction in Mortality Risk。

Janssen Research & DevelopmentTumorCraig Tendler, Ph.D., Vice President of Clinical Development and Global Medical Affairs, stated: “Imbruvica is the most comprehensively studied BTK inhibitor to date, with the longest follow-up duration across eight positive Phase 3 trials in CLL, and is recognized as a significant advance in the treatment of patients with CLL. This latest milestone underscores our commitment to investigating the full potential of Imbruvica and to developing therapies that can transform CLLDiagnosis“a regimen of significance for the patient’s future.”

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 essential 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 severe debilitating diseases.

Imbruvica blocks the signaling pathways that mediate uncontrolled B-cell proliferation and dissemination, helping to kill cancer cells, reduce their numbers, and delay disease progression. InClinical Trialsin China, monotherapy and combination therapies targeting a wide range of hematologic malignanciesTumorDemonstrated robust efficacy.

Since its launch in 2013, Imbruvica has received 11 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 deletion 17p mutation (del17p), small lymphocytic lymphoma (SLL) with or without deletion 17p mutation (del17p), Waldenström macroglobulinemia (WM), previously treated mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) requiring systemic therapy and having received at least one anti-CD20 therapy, and chronic graft-versus-host disease (cGVHD) refractory to one or more systemic therapies.

Currently, AbbVie and Johnson & Johnson are advancing a large-scale Imbruvica clinicalTumorProject Development. The industry holds a very optimistic view of the commercial prospects for Imbruvica. An article titled “Top product forecasts for 2020,” published in January in the premier international journal Nature Reviews Drug Discovery, predicted that global sales of Imbruvica would reach $6.818 billion in 2020. In late June, the pharmaceutical market research firm EvaluatePharma released a forecast report stating that, with continuous market penetration and an expanding range of indications, Imbruvica’s sales are projected to reach $10.722 billion by 2026, making it the fifth best-selling drug worldwide. (Bioon.com)

Original Source: Janssen Announces European Commission Decision for Expanded Use of IMBRUVICA (ibrutinib) in Combination with Rituximab for Previously Untreated Patients with Chronic Lymphocytic Leukaemia (CLL)