Janssen-Cilag UK (Janssen) announced today that the European Commission (EC) has approved IMBRUVICA® (ibrutinib) as a treatment option for 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.1 Prior to this decision there were no EC-approved treatment options available for patients with this rare and slow-growing blood cancer.2

WM is a rare type of slow-growing non-Hodgkin lymphoma. It develops when plasma cells, specialised immune cells that produce antibodies, grow out of control.3 In the UK, over 400 patients each year are diagnosed with this disease, which is most prevalent in men over 65 years of age.4 WM accounts for approximately 2% of all B-cell lymphomas diagnosed in the UK each year.5 The incidence rates among men and women in Europe are approximately 7.3 and 4.2 per million persons, respectively.6

Dr Rebecca Auer, Clinical Senior Lecturer at Queen Mary University, said: "The EU licence for ibrutinib in Waldenström's Macroglobulinemia is exciting, as it is the first licensed treatment for this rare disease in the UK. Ibrutinib is an oral and chemotherapy free approach, which has a good response rate and a generally well tolerated safety profile in clinical trials.7 This is particularly important because drug toxicities can have such a significant impact on a patient's quality of life."

Roger Brown, Chair of Waldenstrom's Macroglobulinemia UK and a long term WM patient, said: "Many patients have run out of effective options for treatment. We warmly welcome the approval of a new treatment option for patients with WM."

WM is the third type of blood cancer in which ibrutinib is indicated, having already been approved in Europe for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), for adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.8 Ibrutinib has also been approved for the treatment of WM by the U.S. FDA, which granted it Breakthrough Therapy Designation in 2013. Investigational uses for ibrutinib, alone and in combination with other treatments, are under way in several blood cancers.

Genome sequencing of patients with WM has revealed a highly prevalent mutation in the MYD88 gene. This mutation triggers the activation of a number of targets, including Bruton's tyrosine kinase (BTK), which is a key component needed to regulate immune cell proliferation and cell survival which plays a part in B-cell malignancies, such as WM.9 Ibrutinib forms a strong covalent bond with BTK, thereby inhibiting the enzyme and blocking the transmission of cell survival signals within the malignant B cells.10

The Phase 2 multi-centre study, on which the European approval was based, evaluated the efficacy and tolerability of ibrutinib 420 mg once-daily in 63 patients with previously treated WM (median age of 63; range, 44-86 years old). Updated results from the study were published on 8 April, 2015 in an online edition of The New England Journal of Medicine.7 The overall response rate using criteria-adopted from the International Workshop on WM was 90.5 percent, 57 out of 63 patients (95% confidence interval [CI], 80.4-96.4). Eleven patients (17 percent) achieved a minor response, 36 patients (57 percent) achieved a partial response (PR) and 10 patients (16 percent) achieved a very good PR. The median times to at least minor and partial responses were four weeks and eight weeks, respectively.7

Secondary endpoints of the registration trial included progression free survival (PFS) and the safety and tolerability of ibrutinib in symptomatic patients with previously treated WM. The estimated two-year PFS and overall survival rates among all patients were 69.1 percent (95% CI, 53.2-80.5), and 95.2 percent (95% CI, 86.0-98.4) respectively.7 The most commonly occurring adverse reaction in the WM trial (8 patients, or 14 percent; P=0.05) was neutropenia (decreased amount of neutrophils in the blood). Thrombocytopenia (decrease in platelets in the blood) occurred in eight patients (13 percent; P=0.01), and other adverse events occurred in less than five patients (<10 percent) each. Four patients (six percent) in the WM trial receiving ibrutinib discontinued treatment due to neutropenia or thrombocytopenia. Additionally these two adverse events led to dose reduction in three patients (five percent).7

For safety information on ibrutinib please go to the following link: https://www.medicines.org.uk/emc/medicine/29383

Mark Hicken, Managing Director Janssen UK, said: "At Janssen, we are delighted to bring patients in the UK the first EC-approved treatment option for Waldenström's Macroglobulinemia, leading the way in delivering innovative, effective and targeted treatment options for those affected by rare blood cancers."

Ibrutinib is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market Ibrutinib 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.

About Ibrutinib

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.10 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells. It also slows down the worsening of the cancer.11

Ibrutinib is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib 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 are continuing an extensive clinical development programme for ibrutinib, including Phase 3 study commitments in multiple patient populations.