FDA expands approval for Johnson & Johnson, Pharmacyclics' Imbruvica in CLL

Johnson & Johnson and Pharmacyclics said Monday that the FDA expanded the indications for Imbruvica (ibrutinib) to include full approval for use in treating patients with chronic lymphocytic leukaemia (CLL) who received at least one prior therapy, and for CLL patients with the 17p deletion, which is associated with poor treatment outcomes. The BTK inhibitor was granted accelerated approval in February for CLL in previously treated patients, and has also been cleared under an accelerated review process for mantle cell lymphoma (MCL).

The companies said the updated labelling is based on results from the Phase III RESONATE trial of 391 patients with CLL or small lymphocytic leukaemia (SLL) who received a median of two prior therapies. Johnson & Johnson noted that 32 percent of study participants carried the 17p deletion. The trial was halted early after an interim analysis showed Imbruvica met its primary goal of significantly improving progression-free survival (PFS), as well as the key secondary endpoint of overall survival (OS), compared with GlaxoSmithKline and Genmab's Arzerra (ofatumumab).

According to the drugmakers, an independent review committee (IRC) identified a 78-percent reduction in the risk of disease progression or death for Imbruvica versus Arzerra, while the OS results represent a 57-percent lower risk of death among patients in the Imbruvica group compared with those given Arzerra. Further, the IRC also determined that Imbruvica was associated with a 75-percent reduced risk of progression or death among carriers of the 17p deletion. John Byrd, lead investigator for the RESONATE trial, said the FDA's decision "is particularly exciting for people with [the 17p deletion], considering Imbruvica is the first treatment to be approved specifically for this difficult-to-treat patient population."

Commenting on the news, Roth Capital analyst Joseph Pantginis said "this new approval and labelling change will continue to strengthen Imbruvica's foothold as a new potential cornerstone in treating B-cell lymphomas." He added that the PFS and OS results from the RESONATE trial suggest "the drug may now be viewed as a real alternative to chemotherapy."

Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, noted that "Imbruvica is the fourth drug approved to treat CLL that received a breakthrough therapy designation." Last week, the agency cleared Gilead Sciences' Zydelig (idelalisib) in combination with Roche's Rituxan (rituximab) to treat CLL patients who have relapsed, and also approved Arzerra earlier this year and Roche's Gazyva (obinutuzumab) last November.

Meanwhile, the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) recommended approval for Imbruvica in adults with CLL who received at least one prior treatment, and for use in the first-line setting to treat patients with a 17p deletion or TP53 mutation that makes them unsuitable for chemo-immunotherapy. The CHMP also backed the drug for use in adults with relapsed or refractory MCL. Johnson & Johnson and Pharmacyclics developed Imbruvica under a 2011 agreement that could be worth as much as $975 million to Pharmacyclics.

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