IMBRUVICA® (ibrutinib) Pooled Outcomes Data from Three Phase 3 Studies Suggest Potential Clinical Efficacy in Patients with High-Risk Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

NORTH CHICAGO, IL, USA I May 14, 2017 I AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced results from an analysis of data pooled from three Phase 3 studies evaluating IMBRUVICA® (ibrutinib) use in patients with high-risk chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): RESONATE^TM, RESONATE^TM-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 (abstract #19). These data will be presented today in an oral presentation at the 17^th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) biennial meeting in New York, NY.

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

“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.¹ 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.² CLL/SLL are predominately a disease of the elderly, with a median age of 71 at diagnosis.³ Genomic abnormalities in CLL, including del 11q, deletion 17p (del 17p), trisomy 12, CK and IGHV, are detected in up to 80 percent of patients and play an important role in disease pathogenesis and evolution, determining patient outcomes and therapeutic strategies.⁶

“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

Abstract #19: Outcomes of Ibrutinib-Treated Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL) with High-Risk Prognostic Factors in an Integrated Analysis of 3 Randomized Phase 3 Studies

• Oral presentation: Sunday, May 14, 2017, 5:00 PM ET

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 percent in unmutated IGHV, 88 percent in del 11q, 86 percent in trisomy 12 and 87 percent in CK, with patients achieving a CR rate of 22 percent in unmutated IGHV, 18 percent in del 11q, 25 percent in trisomy 12 and 10 percent in CK. At 24 months, in patients treated with IMBRUVICA, PFS was 78 percent in unmutated IGHV, 82 percent in del 11q, 77 percent in trisomy 12 and 76 percent in CK. In patients treated with IMBRUVICA, at 30 months, OS was 88 percent in unmutated IGHV, 93 percent in del 11q, 89 percent in trisomy 12 and 84 percent in CK.³

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 percent at 24 months for those with del 11q, compared with 75 percent for those without del 11q) and OS (93 percent at 30 months for those with del 11q, compared with 86 percent for those without del 11q) and trisomy 12 with increased CR rate (25 percent for those with trisomy 12, compared with 6 percent 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.³

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.³

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 percent in IMBRUVICA-treated patients and 13-17 percent in comparator-treated patients.³

P-values ranged from 0.03-0.96. To view more abstract data, including all P-values, see Table 1 and Table 2 at the end.

About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.^4,5 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.⁴

IMBRUVICA is FDA-approved in five distinct patient populations: CLL, SLL, WM, along with previously-treated MCL and MZL.⁴

• IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
• Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
• IMBRUVICA was approved for patients with WM in January 2015.
• In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
• In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.

Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.⁴

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, more than 65,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

Table 1.  Number of Patients with Cancer-Cell Genomic Data

Table 2. Efficacy Outcomes in Ibrutinib- and Comparator-Treated Patients by Genomic Prognostic Factors (Univariate)

SOURCE: AbbVie