FDA Expands Approved Use of Ibrutinib for Chronic Lymphocytic Leukaemia

New clinical data supports treatment of CLL patients with 17p deletion, which is associated with poor responses to standard treatment

The US Food and Drug Administration (FDA) on 28 July 2104 expanded the approved use of ibrutinib (Imbruvica) to treat patients with chronic lymphocytic leukaemia (CLL) who carry a deletion in chromosome 17 (17p deletion), which is associated with poor responses to standard treatment for CLL. Ibrutinib received a breakthrough therapy designation for this use.

The FDA is also approving new labelling to reflect that ibrutinib’s clinical benefit in treating CLL has been verified. In February 2014, ibrutinib received accelerated approval to treat CLL based on its effect on overall response rate. New clinical trial results examining progression-free survival and overall survival have confirmed the drug’s clinical benefit.

CLL is a rare blood and bone marrow disease that usually gets worse slowly over time, causing a gradual increase in B lymphocytes. Ibrutinib works by blocking the enzyme that allows cancer cells to grow and divide.

“We continue to see advances in the availability of therapies to treat chronic lymphocytic leukemia, especially for difficult-to-treat patient populations,” said Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Imbruvica is the fourth drug approved to treat CLL that received a breakthrough therapy designation, reflecting the promise of the breakthrough therapy designation program and demonstrating the FDA’s commitment to working cooperatively with companies to expedite the development, review and approval of these important new drugs.” 

The other three drugs approved to treat CLL that received breakthrough designations are obinutuzumab (Gazyva) in November 2013, ofatumumab (Arzerra) in April 2014 and idelalisib (Zydelig) in July 2014. Ibrutinib’s application for accelerated approval to treat CLL did not receive breakthrough therapy designation.

The new approval actions for ibrutinib are based on a clinical study of 391 previously treated participants, 127 of whom had CLL with 17p deletion. Participants were randomly assigned to receive ibrutinib or ofatumumab until disease progression or side effects became intolerable. 

The trial was stopped early for efficacy after a pre-planned interim analysis showed ibrutinib-treated participants experienced a 78% reduction in risk of disease progression or death (progression-free survival). Results also showed a 57% reduction in risk of death (overall survival) in participants treated with ibrutinib. Of the 127 participants who had CLL with 17p deletion, those treated with ibrutinib experienced a 75% reduction in risk of disease progression or death.

The most common side effects associated with ibrutinib observed in the clinical study include thrombocytopenia, neutropaenia, diarrhea, anaemia, fatigue, musculoskeletal pain, upper respiratory tract infection, rash, nausea and pyrexia. 

Ibrutinib’s new use is being approved more than two months ahead of the product’s prescription drug user fee goal date of 7 October, 2014, the date the FDA was scheduled to complete review of the drug application. The FDA reviewed ibrutinib’s application for this new use under the agency’s priority review programme, which provides for an expedited review of drugs that are intended to treat a serious disease or condition and, if approved, would offer significant improvement compared to marketed products. 

Ibrutinib also received accelerated approval in November 2013 for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. Clinical studies to verify and describe ibrutinib’s clinical benefit in mantle cell lymphoma are ongoing. 

Imbruvica is co-marketed by Pharmacyclics and Janssen Biotech.