Imbruvica(ibrutinib)

Imbruvica (ibrutinib) is a drug initially approved in November 2013 in the U.S. for various indications, including accelerated approval for mantle cell lymphoma (MCL) and marginal zone lymphoma. It is approved in 70 countries. The recommended dose for MCL is 560 mg, while for chronic lymphocytic leukemia (CLL) and Waldenström's macroglobulinemia (WM) it is 420 mg once daily.

In an MCL trial with 111 patients, the overall response rate (CR+VGPR+PR) per IRRC assessment was 61.9%, with a 95% CI of 49% to 74%. The median duration of response was not reached, with a median follow-up of 11.8 months. The duration of response ranged from 2.8+ to 18.8+ months. In a CLL trial (Study 2) with 391 randomized patients, the median duration of IMBRUVICA exposure was 8.6 months, compared to 5.3 months for ofatumumab exposure.

Safety findings include Grade 3 or higher bleeding events in 6% of patients, and bleeding events of any grade in approximately half of patients. Grade 3 or greater infections occurred in 14% to 26% of patients. Treatment-emergent Grade 3 or 4 neutropenia ranged from 19% to 29%, and Grade 3 or 4 thrombocytopenia from 5% to 17%. Atrial fibrillation and atrial flutter were observed in 6% to 9% of patients. A Cmax decrease was noted for tablet formulations compared to capsules, specifically 10.2% for the 140mg dose and 27.7% for the 520mg dose.