FDA Expands Approved Use of Ibrutinib to Waldenström’s Macroglobulinaemia

First drug approved by FDA to treat Waldenström’s macroglobulinaemia

On 29 January, 2015 the USA Food and Drug Administration (FDA) expanded the approved use of ibrutinib (Imbruvica) to treat patients with Waldenström’s macroglobulinaemia. The drug received a breakthrough therapy designation for this use.

Waldenström’s macroglobulinaemia is a rare disease. It accounts for 1%–2% of haematological neoplasms with a reported age-adjusted incidence rate of 3.4 per million among males and 1.7 per million among females in the USA and 7.3 and 4.2 per million European standard population. Waldenström’s macroglobulinaemia is a disease of the elderly with a median age of 63–68 years with a male predominance.

To establish the diagnosis of Waldenström’s macroglobulinaemia, it is necessary to demonstrate an immunoglobulin M (IgM) monoclonal protein, along with histological evidence of infiltration of the bone marrow by lymphoplasmacytic cells in line with the diagnosis of lymphoplasmacytic lymphoma.

Waldenström’s macroglobulinaemia usually gets worse slowly over time and causes abnormal B lymphocytes (B-cells) to grow within the bone marrow, lymph nodes, liver, and spleen. In Waldenström’s macroglobulinaemia, abnormal B-cells overproduce IgM that may lead to excess bleeding, problems with vision and with the nervous system.

Ibrutinib is orally-administered, selective and covalent inhibitor of the enzyme Bruton’s tyrosine kinase.

The FDA initially granted ibrutinib accelerated approval in November 2013 for use in patients with mantle cell lymphoma who received one prior therapy. In February 2014, the FDA granted accelerated approval to ibrutinib for use in patients with previously treated chronic lymphocytic leukaemia (CLL), and then in July 2014, expanded its use to include treatment of CLL patients who carry a deletion in chromosome 17.

The FDA based its approval of ibrutinib for Waldenström’s macroglobulinaemia on a clinical study of 63 previously treated participants. All study participants received a daily 420 mg orally administered dose of the medication until disease progression or side effects became intolerable. Results showed 62% of participants had overall response rate. At the time of the study, the duration of response ranged from 2.8 months to approximately 18.8 months.

The most common side effects associated with the drug are thrombocytopaenia, neutropaenia, diarrhoea, anaemia, fatigue, musculoskeletal pain, bruising, nausea, upper respiratory tract infection, and rash.

Healthcare professionals should inform their patients of the risk for hemorrhage, infections, atrial fibrillation, second primary malignancies, tumour lysis syndrome, and embryo-fetal toxicity associated with the use of ibrutinib.

The FDA granted ibrutinib for Waldenström’s macroglobulinaemia breakthrough therapy designation, priority review, and orphan product designation because the company demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; has potential, at the time of the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively.

The product’s new use is being approved more than two months ahead of its prescription drug user fee goal date of April 17, 2015, the date the FDA was scheduled to complete review of the drug application.

Imbruvica is co-marketed by Pharmacyclics, based in Sunnyvale, California, and Janssen Biotech, based in Horsham, Pennsylvania.