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U.S. FDA Approves Imbruvica (ibrutinib) as First Treatment Specifically Indicated for Relapsed/Refractory Marginal Zone Lymphoma (MZL)

NORTH CHICAGO, Ill., Jan. 19, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced the U.S. Food and Drug Administration (FDA) approved Imbruvica (ibrutinib) for the treatment of patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.1 This indication is approved under accelerated approval based on overall response rate (ORR), and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. Imbruvica is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

"The FDA approval of Imbruvica for relapsed/refractory marginal zone lymphoma is significant, and we are proud of the culmination of this extensive clinical research program, representing the first approved treatment specifically for patients with this rare type of non-Hodgkin's lymphoma," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics LLC, an AbbVie company. "This milestone marks the fifth patient population for whom Imbruvica is now approved and broadens the number of patients who may be treated with the medication. We continue to research Imbruvica across many disease areas, including but not limited to other B-cell malignancies."

The approval in MZL is based on data from the Phase 2, open-label, multi-center, single-arm PCYC-1121 study, which evaluated the safety and efficacy of IMBRUVICA in MZL patients who require systemic therapy and have received at least one prior anti-CD20-based therapy. The efficacy analysis included 63 patients with three sub-types of MZL: mucosa-associated lymphoid tissue (MALT; N=32), nodal (N=17) and splenic (N=14). The ORR was achieved in nearly half (46%) of the patients (95% CI: 33.4-59.1) as assessed by an Independent Review Committee (IRC) using criteria adopted from the International Working Group criteria for malignant lymphoma, with efficacy observed across all three MZL sub-types. The median time to response was 4.5 months (range, 2.3-16.4 months). In the trial, 3.2% of patients had a complete response (CR) and 42.9% of patients had a partial response (PR). The median duration of responses was not reached (NR) (range 16.7 months to NR).1 The data were previously presented at the American Society of Hematology (ASH) Annual Meeting (December 2016).

"In the Phase 2 trial, Imbruvica demonstrated impressive response rates and duration of response in relapsed/refractory marginal zone lymphoma patients," said Ariela Noy, M.D., Hematologic Oncologist at Memorial Sloan Kettering Cancer Center in New York and lead investigator of the study.* "The hematology-oncology community welcomes a new option like Imbruvica, which helps fill a significant treatment gap for previously treated MZL patients who are in need of non-chemotherapy options."

Overall, the safety data from this study was consistent with the known safety profile of IMBRUVICA in B-cell malignancies. The most common adverse events (AEs) of all Grades (occurring in ?20% of MZL patients treated with Imbruvica) included thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema and arthralgia (24% each), neutropenia and cough (22% each), and dyspnea and upper respiratory tract infection (21% each). The most common (>10%) Grade 3 or 4 AEs were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).1

The risks associated with Imbruvica as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome and embryo fetal toxicities.

Imbruvica is now approved to treat patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy, as well as patients with other non-Hodgkin's lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including patients with 17p deletion; patients with mantle cell lymphoma (MCL) who have received at least one prior therapy; and patients with Waldenström's macroglobulinemia (WM).1 Continued approval for the MZL and MCL indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the Study

The Phase 2 PCYC-1121 trial is a Pharmacyclics-sponsored study that evaluated the safety and efficacy of ibrutinib in patients with R/R MZL. The primary objective of the trial was ORR as assessed by an IRC. Duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety were secondary objectives.2

About Marginal Zone Lymphoma

Marginal zone lymphoma (MZL) is a slow-growing B-cell lymphoma arising from white blood cells (lymphocytes) at the edges of lymphoid tissue.3 MZL accounts for approximately 8% of all cases of non-Hodgkin's lymphoma in adults, and the median age of diagnosis is 65 years old.3,4 There are three sub-types of MZL: mucosa-associated lymphoid tissue, nodal and splenic.3

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.1,5 Imbruvica blocks signals that tell malignant B cells to multiply and spread uncontrollably.1

Imbruvica is FDA-approved in five distinct patient populations: CLL, SLL, WM, along with previously-treated MCL and MZL.1

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 patients with previously treated CLL/SLL.

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 indication based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.1

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 nearly 30 company-sponsored trials underway, 14 of which are Phase 3. In addition, there are approximately 100 investigator-sponsored trials and external collaborations that are ongoing and 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-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements

Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

Imbruvica is a registered trademark of Pharmacyclics LLC

*Disclaimer: Dr. Noy served as an investigator of this Pharmacyclics-sponsored clinical study. Dr. Noy does not have a financial interest in the company.

1 IMBRUVICA US Prescribing Information, January 2017.
2 Noy, A, et al. Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study. ASH 2016. Abstract #1213.
3 Lymphoma Research Foundation. "Marginal Zone Lymphoma." Available from: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6554677. Accessed January 2017.
4 Lymphoma Research Foundation. "Getting the Facts: Marginal Zone Lymphoma." Available from: http://www.lymphoma.org/atf/cf/%7baaf3b4e5-2c43-404c-afe5-fd903c87b254%7d/lrf_factsheet_marginal_zone_lymphoma.pdf. Accessed January 2017.
5 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed January 2017.

SOURCE AbbVie

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