Janssen-Cilag International NV (Janssen) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the granting of a marketing authorisation for IMBRUVICA™ (ibrutinib) in the European Union. The recommendation is for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), or 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. The positive opinion of the CHMP was based on data from the Phase 3 (RESONATE™ PCYC-1112) and Phase 1b-2 (PCYC-1102) studies in CLL, and the Phase 2 study (PCYC-1104) in MCL.
Ibrutinib is being co-developed by Janssen and Pharmacyclics Switzerland GmbH. Once approved, Janssen will market ibrutinib in EMEA (Europe, Middle East, Africa) as well as the rest of the world, except for the United States, where both companies co-market it.
MCL is a rare and aggressive type of B-cell lymphoma that can be challenging to treat and is associated with a poor prognosis. CLL in most patients is a slow-growing blood cancer, starting from white blood cells (called lymphocytes) in the bone marrow. Chromosomal abnormalities deletion 17p (del17p) and TP53 mutation are associated with aggressive, treatment-resistant disease.
Ibrutinib is a novel, investigational compound that could offer a new approach to treating these blood cancers, as part of a class of medicines called Bruton’s Tyrosine Kinase (BTK) inhibitors. Studies have shown ibrutinib works by blocking BTK, a protein that helps certain cancer cells live and grow.
“We are working to bring new therapies to patients living with complex and challenging-to-treat blood cancers. We’ve been closely collaborating with the CHMP on the IMBRUVICA submission and are delighted to receive the positive opinion earlier than expected. There is a high unmet medical need and recent clinical trials have demonstrated positive results for IMBRUVICA,” said Jane Griffiths, Company Group Chairman, Janssen, Europe, Middle East and Africa (EMEA). "The CHMP opinion brings us one step closer to offering new treatment options for CLL and MCL patients.”
CLL Study and Efficacy Results
RESONATE™ (PCYC-1112) is a Phase 3, multi-centre, international, open-label, randomised study that examined ibrutinib monotherapy versus ofatumumab monotherapy in relapsed or refractory patients with CLL (n=391).
The results from the study showed single agent ibrutinib significantly improved progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in this difficult-to-treat patient population, regardless of baseline characteristics.
The median PFS in the ofatumumab arm was 8.1 months and was not reached in the ibrutinib arm because progression events occurred more slowly. The PFS results represent a 78 percent reduction in the risk of progression or death in patients treated with ibrutinib compared to ofatumumab. The OS median was not reached in either arm, but the results represent a 57 percent reduction in the risk of death in patients receiving ibrutinib versus those in the ofatumumab arm. Results were consistent across all baseline sub-groups, including those with del17p.
MCL Study and Efficacy Results
The efficacy of ibrutinib in patients with relapsed or refractory MCL was evaluated in an open-label, multi-centre, single-arm Phase 2 study (PCYC-1104) of 111 treated patients. A response rate of 68 percent was observed, with a complete response rate of 21 percent and a partial response rate of 47 percent. With a median follow up of 15.3 months, the median duration of response was 17.5 months; the median progression-free survival was 13.9 months.
CLL and MCL Safety Results
The most commonly occurring adverse reactions (≥ 20%) were diarrhoea, musculoskeletal pain, upper respiratory tract infection, bruising, rash, nausea, pyrexia (fever), neutropenia (abnormally low number of white blood cells) and constipation. The most common grade 3/4 adverse reactions (≥ 5%) were anaemia, neutropenia, pneumonia and thrombocytopenia (low platelet count).
The CHMP's positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorisation for medicines in the European Economic Area. A final decision on ibrutinib by the European Commission is anticipated later this year.