Janssen Receives CHMP Positive Opinion for Imbruvica (Ibrutinib) Plus Rituximab as First-Line Treatment for Chronic Lymphocytic Leukemia

Jul 27, 2020 11:37 CST Updated Jul 26, 13:43

Janssen Pharmaceuticals

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

July 26, 2020 News /BioValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Imbruvica (ibrutinib) in combination with rituximab for the first-line treatment of chronic lymphocytic leukemia.Leukemia(CLL) adult patients. Now, the CHMP's positive opinion will be reviewed by the European Commission (EC), which typically makes a final decision within two months.

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

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. To date, Imbruvica has been used to treat more than 200,000 patients worldwide across its approved indications.

The CHMP's positive review opinion andFDAThe approvals were all based on the results of the Phase III E1912 study (NCT02048813). This study evaluated a total of 529 patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). In the study, these patients were randomly assigned to receive either the Imbruvica plus rituximab regimen (IR, n=354) or chemoimmunotherapy (FCR: fludarabine, cyclophosphamide, and rituximab; n=175). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS).

The primary results of this study have been published in The New England Journal of Medicine (NEJM). The results demonstrated that, compared with the FCR treatment group, the Imbruvica plus rituximab treatment group showed significantly improved progression-free survival (PFS) and overall survival (OS). The safety data from the study were consistent with the known safety profile of Imbruvica.

The four-year follow-up results of this study were presented at the 2019 American Society of Hematology (ASH) Annual Meeting. With a median follow-up of 48 months, 73% of patients in the IR regimen group remained on 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 demonstrated sustained superior PFS benefits (HR=0.39 [95% CI: 0.26–0.57], p<0.0001), with a 61% reduction in the risk of disease progression or death. Furthermore, compared with the FCR regimen group, the IR regimen group showed sustained superior OS benefits (HR=0.34; 95% CI: 0.15–0.79; p=0.009), with a 66% reduction in the risk of death.

In terms of safety, the proportions of patients experiencing grade 3 or higher treatment-related adverse events (TEAEs) were 70% in the IR regimen group and 80% in the FCR regimen group (odds ratio [OR]=0.56; 95% CI: 0.34-0.90; p=0.013).

6 Diseases, 11 Indications: Sales to Reach $6.8 Billion in 2020 and $10.7 Billion in 2026

Imbruvica is a small-molecule drug administered orally once daily, which exerts its anticancer effects primarily by inhibiting Bruton’s tyrosine kinase (BTK), an enzyme 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 and 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 Trialin monotherapy and combination therapy for a broad 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 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) refractory to one or more systemic therapies.

Currently, AbbVie and Johnson & Johnson are advancing a large-scale Imbruvica clinicalTumorDevelopment Project. The industry holds a highly optimistic view of Imbruvica's commercial prospects. In January this year, an article titled "Top product forecasts for 2020" published in the prestigious international journal Nature Reviews Drug Discovery predicted that Imbruvica's global sales 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 Receives CHMP Positive Opinion for Expanded Use of IMBRUVICA (ibrutinib) in Combination with Rituximab for Previously Untreated Patients with Chronic Lymphocytic Leukaemia (CLL)