Janssen-Cilag International NV announced the submission of a Type II variation application to the European Medicines Agency (EMA) seeking to broaden the existing marketing authorisation for  Imbruvica (ibrutinib) to include previously untreated patients with chronic lymphocytic leukaemia (CLL).

Imbruvica is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market Imbruvica in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where Janssen Biotech, Inc. and Pharmacyclics LLC co-market it.

The filing is based on data from the randomised, multi-centre, open-label phase 3 RESONATETM-2 (PCYC-1115) clinical trial assessing the use of Imbruvica versus chlorambucil in patients with treatment-naïve CLL or small lymphocytic lymphoma (SLL) aged 65 years or older.

The RESONATE-2 trial, which was sponsored by Pharmacyclics LLC, enrolled 269 patients in the US, EU and other regions. Patients were randomised to receive either Imbruvica 420 mg orally, once daily until progression or toxicity, or chlorambucil 0.5 to 0.8 mg/kg on days 1 and 15 of each 28-day cycle for up to 12 cycles. At the time of the final analysis the primary endpoint was met, with Imbruvica shown to be superior to chlorambucil in terms of progression-free survival (PFS). In addition, Imbruvica demonstrated significant improvements in key secondary efficacy endpoints, including overall survival (OS), overall response rate (ORR) and in haematologic function. The safety findings were consistent with previous studies.

The data have been accepted for presentation at an upcoming medical conference and for publication in a peer-reviewed journal. More information about the study can be found on www.clinicaltrials.gov. On September 14, 2015, Janssen announced that a supplemental New Drug Application (sNDA) was filed with the US Food and Drug Administration for treatment-naïve patients with CLL based on these data.

"This submission to expand the use of Imbruvica for patients with treatment-naïve CLL is a significant step forward in transforming the treatment journey for these patients," said Jane Griffiths, company group chairman, Janssen Europe, Middle East and Africa.

"Our ongoing efforts to further investigate Imbruvica in additional populations is part of our commitment to improving outcomes for patients with difficult to manage cancers."

Imbruvica (ibrutinib) is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B cells. By blocking this BTK protein, Imbruvica helps kill and reduce the number of cancer cells. It also slows down the worsening of the cancer.

Imbruvica is currently approved in Europe for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL); adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or in first line patients with CLL in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy; and in adult patients with Waldenström's macroglobulinemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. Regulatory approval for additional uses has not yet been granted. Investigational uses for ibrutinib, alone and in combination with other treatments, are under way in several blood cancers including CLL, MCL, WM, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), multiple myeloma (MM) and marginal zone lymphoma (MZL).

Imbruvica  is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market Imbruvica in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where Janssen Biotech, Inc. and Pharmacyclics LLC co-market it. Janssen and Pharmacyclics LLC are continuing an extensive clinical development programme for  Imbruvica , including phase 3 study commitments in multiple patient populations.

In most patients, CLL is generally a slow-growing blood cancer of the white blood cells called B-lymphocytes. The median age at diagnosis is 72 years, and incidence rates among men and women in Europe are approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively. CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years according to the stage of disease. The disease eventually progresses in the majority of patients, and patients are faced with fewer treatment options each time. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

CLL cells are found in both the lymphatic system and the blood. When the cancer cells are located mostly in the lymph nodes, the disease is called small lymphocytic lymphoma (SLL). Both CLL and SLL are considered different manifestations of the same entity, as classified in the fourth edition of the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues.