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FDA Approves Imbruvica (ibrutinib) Plus Rituximab for the Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)

NORTH CHICAGO, Ill., April 21, 2020 – AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) approved the use of Imbruvica® (ibrutinib) in combination with rituximab for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This milestone marks the 11th FDA approval for Imbruvica since it was first approved in 2013 and the sixth in CLL, the most common form of leukemia in adults.1

“The gold-standard first-line treatment option for many patients with chronic lymphocytic leukemia who were fit enough to tolerate an aggressive treatment course had been the intravenous chemoimmunotherapy of FCR – that is, until today,” said Brian Koffman, M.D., C.M., Chief Medical Officer and Executive Vice President, CLL Society. “The FDA approval of ibrutinib and rituximab regimen is welcome news for these previously untreated patients who have been looking forward to a non-chemotherapy treatment option. The results from ECOG-ACRIN’s E1912 clinical trial in previously untreated, younger adult patients and today’s milestone represent a paradigm shift in how physicians can treat patients with CLL and may enable many to choose a non-chemotherapy treatment option."

The approval is based on positive results from the landmark Phase 3 E1912 study, which was designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). This is the third Phase 3 randomized study in the treatment of previously untreated CLL patients incorporated into the medicine’s U.S. prescribing information. In addition to the Real-Time Oncology Review (RTOR) pilot program and priority review, the approval was granted under the FDA’s recently established Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for submission and review of oncology medicine applications among multiple regulatory agencies worldwide.

“With eleven FDA approvals in six years, this latest CLL label update for Imbruvica further underscores the impact of this important medicine in the first-line setting,” said Danelle James, M.D., M.A.S., Imbruvica Clinical Development Lead, Pharmacyclics LLC, an AbbVie company. “Imbruvica enables long-term disease management and now has demonstrated superior progression-free survival compared to a standard chemoimmunotherapy regimen. Today, many patients who were previously considered appropriate for chemotherapy now have an alternative treatment option.”

The E1912 study demonstrated previously untreated patients (aged 70 or younger) with CLL lived longer without disease progression – as measured by statistically significant progression-free survival (PFS) – with Imbruvica plus rituximab compared to those treated with the potent chemoimmunotherapy regimen comparator of fludarabine, cyclophosphamide and rituximab (FCR). At a median follow-up of 37 months, Imbruvica plus rituximab significantly improved PFS compared to FCR (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.22-0.52; p<0.0001). With a median follow-up time of 49 months, median overall survival was not reached with a total of 23 deaths: 11 (3%) in the Imbruvica plus rituximab and 12 (7%) in the FCR treatment arms. Extended follow-up results from the E1912 study were most recently presented in an oral session at the 2019 American Society of Hematology (ASH) Annual Meeting.

In the E1912 study, the most common adverse reactions (occurring in 30% or more of patients) of all Grades in patients treated with Imbruvica plus rituximab compared to patients treated with FCR were fatigue (80% vs. 78%), musculoskeletal pain* (61% vs. 35%), diarrhea (53% vs. 27%), rash* (49% vs. 29%), hypertension* (42% vs. 22%), arthralgia (41% vs. 10%), nausea (40% vs. 64%), headache (40% vs. 27%), bruising* (36% vs. 4%), cough (32% vs. 25%) and hemorrhage* (31% vs. 8%).

The recommended dosage of Imbruvica for CLL/SLL is 420 mg orally once a day until disease progression or unacceptable toxicity. For adults with CLL/SLL, Imbruvica can be administered as a single agent, in combination rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR). When administering Imbruvica in combination with rituximab or obinutuzumab, consider administering Imbruvica prior to rituximab or obinutuzumab when given on the same day.

*Includes multiple adverse drug reaction terms.

About the E1912 Study2 

The Phase 3 E1912 study evaluated 529 previously untreated CLL patients ages 70 or younger (median age of 58) who were randomly assigned in a 2:1 fashion to receive Imbruvica plus rituximab (N=354) or the chemoimmunotherapy FCR (N=175). The primary endpoint was PFS.

The study was led by ECOG-ACRIN with study site participation by groups in the NCI's National Clinical Trials Network (Alliance for Clinical Trials in Oncology, ECOG-ACRIN, NRG Oncology and SWOG), and was sponsored by the NCI. Pharmacyclics LLC supported the study through a Cooperative Research and Development Agreement with the NCI.

About Imbruvica

Imbruvica is a once-daily, first-in-class Bruton's tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company and Janssen Biotech, Inc. The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.3,4 By blocking BTK, Imbruvica may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.5

Since its launch in 2013, Imbruvica has received 11 FDA approvals across six disease areas:

chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström’s macroglobulinemia (WM); previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.6

Imbruvica is now approved in 95 countries and has been used to treat more than 195,000 patients worldwide across its approved indications. Imbruvica is the only FDA-approved medicine in WM and cGVHD. Imbruvica has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. Imbruvica was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

In early 2019, the National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (Imbruvica) as a preferred regimen for the initial treatment of CLL/SLL and it is the only Category 1 treatment for treatment-naïve patients without deletion 17p. In February 2020, the NCCN Guidelines® were updated to elevate Imbruvica with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL.

Imbruvica is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. Imbruvica is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com.

*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.

About AbbVie

AbbVie is a global, research and development-based 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, LinkedIn or Instagram.

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.

  1. 1 American Society of Hematology. Leukemia. http://www.hematology.org/Patients/Cancers/Leukemia.aspx. Accessed February 2020.
    2 Shanafelt, T., et al. Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. The New England Journal of Medicine. August 1, 2019. https://www.nejm.org/doi/full/10.1056/NEJMoa1817073. Accessed January 2020.
    3 Genetics Home Reference. Isolated growth hormone deficiency. http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed January 2020.
    4 Turetsky, et al. Single cell imaging of Bruton's Tyrosine Kinase using an irreversible inhibitor. Scientific Reports. volume 4, Article number: 4782 (2014).
    5 de Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594.
    6 IMBRUVICA U.S. Prescribing Information, April 2020. 

SOURCE AbbVie Inc.

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