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AbbVie reported Imbruvica CLL/SLL data

Wednesday, May 17, 2017

AbbVie, a global biopharmaceutical company, announced results from an analysis of data pooled from three phase III studies evaluating Imbruvica (ibrutinib) use in patients with high-risk chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): RESONATE, RESONATE-2 and HELIOS.

In this analysis, CLL/SLL patients with genomic abnormalities that typically put them at high risk for poor outcomes achieved higher complete response (CR) rates and overall response rates (ORR), as well as longer progression free survival (PFS) at 24 months and overall survival (OS) at 30 months, when treated with Imbruvica versus comparator-treated patients. In RESONATE, patients received Imbruvica or ofatumumab; in RESONATE-2, patients received Imbruvica or chlorambucil; and in HELIOS, patients received Imbruvica plus bendamustine and rituximab (BR) or placebo plus BR.

The high-risk genomic abnormalities reviewed were deletion 11q (del 11q), trisomy 12, complex karyotype (CK) and unmutated immunoglobulin heavy-chain variable-region (IGHV). In Imbruvica -treated patients, the presence of del 11q was associated with trends of longer PFS and OS than patients without del 11q when treated with Imbruvica.

Imbruvica, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics, an AbbVie company and Janssen Biotech.

“Over the past few years, we’ve seen tremendous improvements in the treatment of people with CLL and SLL. Newly introduced medications can improve the outcome of therapy, particularly for patients with high-risk prognostic markers who typically do not respond well to standard chemotherapy,” said Thomas J. Kipps, M.D., Ph.D., University of California San Diego, Moores Cancer Center and lead investigator of the study. “Analysis of the clinical data suggests an improvement in outcomes for certain high-risk CLL/SLL patients treated with Imbruvica.”

CLL is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The cancer (leukemia) cells start in the bone marrow but then go into the blood. There are approximately 19,000 newly diagnosed CLL patients every year. SLL is a slow-growing lymphoma biologically similar to CLL in which too many immature white blood cells cause lymph nodes to become larger than normal. CLL/SLL are predominately a disease of the elderly, with a median age of 71 at diagnosis. Genomic abnormalities in CLL, including del 11q, deletion 17p (del 17p), trisomy 12, CK and IGHV, are detected in up to 80% of patients and play an important role in disease pathogenesis and evolution, determining patient outcomes and therapeutic strategies.

“We are encouraged by the findings from these analyses, which add to the large body of data supporting Imbruvica in treating CLL/SLL patients,” said Danelle James, M.D., M.S., head of Clinical Science, Pharmacyclics LLC, an AbbVie company. “We have one of the most robust databases for a single molecule in hematological oncology and more than 25,000 CLL patients have been treated in the U.S. alone with Imbruvica since approval in 2014. We continue to investigate the use of Imbruvica in high-risk patients so that ideally they too can achieve better response rates and overall outcomes to treatment.”

About the Study

Data from three studies, RESONATE, RESONATE-2 and HELIOS, were pooled to analyze the outcomes of Imbruvica and comparator-treated patients when separated on the basis of genomic abnormality. The ORR in patients treated with Imbruvica was 89% in unmutated IGHV, 88% in del 11q, 86% in trisomy 12 and 87% in CK, with patients achieving a CR rate of 22% in unmutated IGHV, 18% in del 11q, 25% in trisomy 12 and 10% in CK. At 24 months, in patients treated with Imbruvica, PFS was 78% in unmutated IGHV, 82% in del 11q, 77% in trisomy 12 and 76% in CK. In patients treated with Imbruvica, at 30 months, OS was 88% in unmutated IGHV, 93% in del 11q, 89% in trisomy 12 and 84% in CK.

In each subgroup, PFS, OS, ORR and CR rates trended higher in Imbruvica-treated patients versus comparator-treated patients, regardless of genomic factors. In Imbruvica-treated patients, unmutated IGHV, del 11q, trisomy 12 or CK were generally not associated with shorter PFS or OS, or decreased ORR or CR rate. Further, in Imbruvica-treated patients, del 11q was associated with a trend of longer PFS (82% at 24 months for those with del 11q, compared with 75% for those without del 11q) and OS (93% at 30 months for those with del 11q, compared with 86% for those without del 11q) and trisomy 12 with increased CR rate (25% for those with trisomy 12, compared with 6% for those without trisomy 12). In a multivariate analysis, ibrutinib-treated patient outcomes in those only having received one or more prior lines of therapy versus treatment in the first-line was associated with shorter PFS and OS.

In RESONATE, patients received Imbruvica 420 mg once daily until disease progression or ofatumumab for up to 24 weeks. In RESONATE-2, patients age 65 or older with treatment-naïve CLL/SLL, not including del 17p, received Imbruvica 420 mg once daily until disease progression, or chlorambucil. In HELIOS, a Janssen-sponsored, randomized, multi-center, double-blind study, previously treated CLL/SLL patients were randomized to receive Imbruvica or placebo, once daily continuing until disease progression or unacceptable toxicity with six cycles of BR.

Adverse events (AEs) were similar in patients with or without genomic factors, and reflect a median treatment exposure of 19-20 months for Imbruvica -treated patients and 5-10 months for comparator-treated patients. Discontinuation due to AEs ranged from 8-15% in Imbruvica-treated patients and 13-17% in comparator-treated patients.

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