European Medicines Agency Issues Positive Recommendation for a New Therapeutic Indication for Ibrutinib

New indication concerns treatment of patients with Waldenström’s macroglobulinaemia

On 21 May 2015, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product ibrutinib (Imbruvica).

The marketing authorisation holder for this medicinal product is Janssen-Cilag International NV.

The CHMP adopted a new indication as follows: “Imbruvica is indicated for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.’’

Imbruvica was first authorised in the European Union in October 2014 for the treatment of chronic lymphocytic leukaemia and mantle cell lymphoma. For information, the full indication will be as follows: 

“Imbruvica is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

Imbruvica is indicated for the treatment of 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.

Imbruvica is indicated for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.”

Imbruvica represents a novel strategy in the treatment of malignancies involving B lymphocytes. The active substance contained in Imbruvica, ibrutinib, works by blocking an enzyme called Bruton’s tyrosine kinase (BTK). By blocking BTK, ibrutinib decreases survival and migration of B lymphocytes, thereby delaying the progression of the cancer.

Imbruvica’s recommendation is based on the results of a phase II study in 63 patients with previously treated Waldenstrӧm’s macroglobulinaemia. Around 90% of the patients treated with Imbruvica responded positively to the treatment and approximately 80% of patients were alive without disease progression after 18 months.

The adverse events reported during the clinical trial were similar to those observed in already approved indications of Imbruvica. They include events affecting the blood and bone marrow such as neutropenia and thrombocytopenia.

Because Waldenstrӧm’s macroglobulinaemia is rare, Imbruvica received an orphan designation for this indication from the Committee for Orphan Medicinal Products in 2014. Orphan designation and the associated incentives such as fee reductions for scientific advice are among the European Medicines Agency’s most important instruments to encourage the development of medicines for patients with rare diseases.

Detailed recommendations for the use of this product will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report, and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.

The opinion adopted by the CHMP at its May 2015 meeting is an intermediary step on Imbruvica’s access to patients with Waldenstrӧm’s macroglobulinaemia. Once the extension of indication has been granted by the European Commission, each Member State will take a decision on price and reimbursement based on the potential role/use of this medicine in the context of its national health system.