FDA expands IMBRUVICA label to include data from two key Phase 3 trials

May 9, 2016 – HORSHAM.  The U.S. Food and Drug Administration (FDA) has approved an expansion to the IMBRUVICA® (ibrutinib) U.S. Prescribing Information (PI) based on data supporting its use in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Janssen announced today.1 The approved label now includes overall survival (OS) data from the Phase 3 RESONATE™-2 (PCYC-1115) trial in treatment-naïve CLL/SLL patients 65 years or older. The updated label also contains clinical data from the Phase 3 HELIOS (CLL3001) trial investigating the use of IMBRUVICA in combination with bendamustine and rituximab (BR) versus placebo plus BR in patients with relapsed or refractory CLL/SLL.

About the IMBRUVICA Label UpdateUpdated data from the RESONATE-2 trial reflect a statistically significant 56 percent reduction in the risk of death with IMBRUVICA compared to chlorambucil after a median follow-up of 28.1 months (HR=0.44 [95 percent CI, 0.21, 0.92]). The RESONATE-2 trial served as the basis for the March 2016 FDA approval of IMBRUVICA as a first-line treatment for patients with CLL.

Additionally, the first data from the HELIOS study on the use of IMBRUVICA in combination with other therapies were added to the label, highlighting the improvement in progression-free survival (PFS) and overall response rate (ORR) when using IMBRUVICA plus BR versus placebo plus BR in patients with relapsed/refractory CLL/SLL. Following a review of the November 2015 supplemental New Drug Application, the FDA has expanded the indication to include the use of IMBRUVICA for SLL patients with or without deletion of the chromosome 17p (del 17p). SLL is a slow-growing lymphoma that is similar to CLL.1,2

“The clinical development plan for IMBRUVICA is very robust and includes many Phase 2 and 3 clinical trials across various indications and combinations,” said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development, LLC. “In partnership with Pharmacyclics, an AbbVie company, we continue to explore the clinical utility of IMBRUVICA and potential benefit it offers to patients with CLL/SLL and other hematologic malignancies.”

“The update helps to affirm the established efficacy, safety and tolerability of this therapy for the treatment of patients with CLL/SLL, both as a monotherapy or in combination with other agents,” said Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and RESONATE-2 study lead investigator. “It reflects the growing body of clinical evidence supporting this therapy as a potential treatment option for people living with CLL/SLL.”

About the RESONATE-2 StudyBuilding on existing positive PFS results from the RESONATE-2 trial, the updated labeling includes information from an additional analysis of the OS data. IMBRUVICA demonstrated a statistically significant 56 percent reduction in the risk of death after a median follow-up of 28.1 months (HR=0.44 [95 percent CI, 0.21, 0.92]). This analysis included 41 percent of patients in the chlorambucil arm who crossed over to receive IMBRUVICA therapy after progressing.

RESONATE-2 is a Pharmacyclics-sponsored, randomized, open-label, international, multi-center Phase 3 study which evaluated the safety and efficacy of IMBRUVICA versus chlorambucil in 269 treatment-naïve patients with CLL/SLL aged 65 years or older. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil 0.5 to 0.8 mg/kg on days 1 and 15 of each 28-day cycle for up to 12 cycles, with an allowance for intrapatient dose increases up to 0.8 mg/kg based on tolerability. The primary endpoint of the study was PFS as assessed by an Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. OS was a key secondary endpoint assessed in the study.

Results from RESONATE-2 were presented in an oral session at the American Society of Hematology (ASH) meeting in Orlando, FL in December 2015 and simultaneously published in The New England Journal of Medicine. The results were also part of the official press program at ASH 2015.

About the HELIOS StudyResults showed the combination of IMBRUVICA plus BR was associated with an 80 percent reduction in the risk of progression or death (HR=0.20 [95 percent CI, 0.15, 0.28, P20 percent) of any Grade in the RESONATE-2 trial for IMBRUVICA were diarrhea (42 percent), musculoskeletal pain* (36 percent), cough (22 percent) and rash* (21 percent). The most common Grade 3/4 AR (>five percent) was pneumonia* (eight percent).

The ARs from the HELIOS trial reported in the IMBRUVICA U.S. PI reflect exposure to IMBRUVICA plus BR with a median duration of 14.7 months versus a median exposure to placebo plus BR of 12.8 months. The most common ARs (>20 percent) of any Grade in the HELIOS trial for IMBRUVICA plus BR were neutropenia* (66 percent), diarrhea (36 percent), thrombocytopenia* (34 percent), musculoskeletal pain* (29 percent), pyrexia (25 percent), rash* (32 percent) and bruising* (20 percent). The most common Grade 3/4 ARs (>five percent) were neutropenia* (61 percent), thrombocytopenia* (16 percent) and hypertension* (five percent).

IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. Janssen and Pharmacyclics continue to support an extensive clinical development program for IMBRUVICA, including a number of Phase 3 study commitments in a variety of patient populations.

About CLL/SLLCLL is a slow-growing blood cancer that most commonly arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow.3,4 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 predominantly a disease of the elderly, with a median age of 71 at diagnosis.5

About IMBRUVICAIMBRUVICA was one of the first therapies to receive U.S. approval after having received the FDA’s Breakthrough Therapy Designation. IMBRUVICA works by blocking a specific protein called Bruton’s tyrosine kinase (BTK).1 The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.1,6 IMBRUVICA targets and blocks BTK, inhibiting cancer cell survival and spread.1 For more information, visit www.IMBRUVICA.com.


1 IMBRUVICA Prescribing Information, May 2016.2 American Cancer Society. Leukemia – Chronic Lymphocytic. Available from: http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf. Accessed May 2016.3 American Cancer Society. Detailed guide: what is chronic lymphocytic leukemia. Available from: http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf. Accessed May 2016.4 Shaffer AL, Rosenwald A, Staudt LM. Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol. 2002;2(12):920-932.5 American Cancer Society. What are the key statistics for chronic lymphocytic leukemia? Available from: http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics. Accessed May 2016.6 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed May 2016.


SOURCE Janssen Biotech, Inc.