AbbVie Announces Fourth Breakthrough Therapy Designation Granted by the U.S. Food and Drug Administration (FDA) for Ibrutinib (IM…
`11/26/2019
`June 29, 2016
`AbbVie Announces Fourth Breakthrough Therapy Designation Granted by the U.S. Food
`and Drug Administration (FDA) for Ibrutinib (IMBRUVICA®) for Chronic Graft-Versus-Host-
`Disease (cGVHD), a Rare Condition with Limited Treatment Options
`
`- FDA also granted ibrutinib Orphan Drug Designation for this condition. There are currently no therapies
`specifically approved for cGVHD, a severe and potentially life-threatening condition in which transplanted cells
`from donor attack the patient's body
`- This latest milestone also highlights the potential benefit of ibrutinib's unique mechanism of action beyond
`oncology
`
`NORTH CHICAGO, Ill., June 29, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical
`company, today announced that the U.S. Food and Drug Administration (FDA) granted a fourth Breakthrough
`Therapy Designation (BTD) for ibrutinib (IMBRUVICA®) as a potential treatment of chronic graft-versus-host-
`disease (cGVHD) after failure of one or more lines of systemic therapy. The FDA also granted the therapy
`Orphan Drug Designation (ODD) for the condition. cGVHD is a severe and potentially life-threatening condition in
`which transplanted cells from the donor attack the patient's body.1 Patients may develop this common
`complication after undergoing allogeneic stem cell or bone marrow transplantation in which they receive cells
`from a donor.1 There are currently no therapies specifically approved for this condition. Most patients with
`cGVHD are prescribed glucocorticoids, a systemic steroid treatment that is able to act upon cells throughout the
`entire body;2 however, research shows that long-term use of steroids can lead to serious health complications.3
`
`The request for a BTD for ibrutinib in patients with cGVHD was based on preliminary clinical data from a Phase
`1b/2 study evaluating the safety and efficacy of ibrutinib for the treatment of patients with steroid-dependent or
`refractory cGVHD. Overall, ibrutinib has shown compelling preclinical data, a novel mechanism of action and
`promising early clinical efficacy data supporting an improvement in cGVHD based on the National Institutes of
`Health (NIH) consensus cGVHD Activity Assessment. Preliminary results from this trial were previously presented
`at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (ESBM) in April 2016
`and the 51st American Society of Clinical Oncology (ASCO) Annual Meeting in May 2015.
`
`According to the FDA, a BTD is intended to expedite the development and review of a potential new drug for
`serious or life-threatening diseases where "preliminary clinical evidence indicates that the drug may demonstrate
`substantial improvement over existing therapies on one or more clinically significant endpoints, such as
`substantial treatment effects observed early in clinical development."4 Similarly, ODD provides special status to a
`therapy developed to treat a rare condition or disease.5
`
`"This fourth Breakthrough Therapy Designation from the FDA shows the promise of IMBRUVICA and its unique
`mechanism of action as a potential therapy beyond blood cancers, including chronic graft-versus-host-disease, a
`severe inflammatory condition with currently no approved therapies specifically for these patients," said Danelle
`James, M.D., M.S., Head of Oncology at Pharmacyclics. "We are committed to continuing to evaluate the
`potential benefit ibrutinib may offer in treating blood cancers, solid tumors and other health conditions with unmet
`medical needs."
`
`In February 2013 (http://www.pharmacyclics.com/docs/librariesprovider4/press-release-archive/2013/pharmacyclics-first-to-announce-
`breakthrough-therapy-designation-in-oncology-from-the-u-s-food-and-drug-administration.pdf?sfvrsn=4) , the FDA granted BTD to
`IMBRUVICA for the treatment of patients with relapsed or refractory mantle cell lymphoma (MCL) and for the
`treatment of patients with Waldenström's macroglobulinemia (WM). In April 2013
`(http://www.pharmacyclics.com/docs/librariesprovider4/press-release-archive/2013/pharmacyclics-announces-third-breakthrough-therapy-
`designation-for-ibrutinib-from-the-u-s-food-and-drug-administration.pdf?sfvrsn=4) , IMBRUVICA was awarded a third BTD for the
`treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with a
`deletion of the short arm of chromosome 17 (del 17p). The Administration also assigned IMBRUVICA ODD for all
`three indications.
`
`IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company and Janssen
`Biotech, Inc.
`About IMBRUVICA
`
`https://news.abbvie.com/article_print.cfm?article_id=11353
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`AbbVie Announces Fourth Breakthrough Therapy Designation Granted by the U.S. Food and Drug Administration (FDA) for Ibrutinib (IM…
`11/26/2019
`IMBRUVICA 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.6,7 IMBRUVICA blocks signals that tell malignant B cells to multiply
`and spread uncontrollably.6
`
`IMBRUVICA is approved to treat patients with CLL/SLL including patients with 17p deletion, patients with MCL
`who have received at least one prior therapy and patients with WM. Accelerated approval was granted for the
`MCL indication based on overall response rate. Continued approval for this indication may be contingent upon
`verification of clinical benefit in confirmatory trials.6
`
`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. More than 6,000 patients have been treated with IMBRUVICA in clinical
`trials. Currently, 14 Phase 3 trials have been initiated with IMBRUVICA and more than 90 trials are registered
`on www.clinicaltrials.gov (http://www.clinicaltrials.gov/) .
`IMPORTANT SAFETY INFORMATION
`WARNINGS AND PRECAUTIONS
`
`Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher
`bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria,
`and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including
`bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA®.
`
`The mechanism for the bleeding events is not well understood. IMBRUVICA® may increase the risk of
`hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for
`signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and
`postsurgery depending upon the type of surgery and the risk of bleeding.
`
`Infections - Fatal and nonfatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections
`occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred
`in patients treated with IMBRUVICA®. Evaluate patients for fever and infections and treat appropriately.
`Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%),
`thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements
`occurred in patients treated with single agent IMBRUVICA®. Monitor complete blood counts monthly.
`Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with
`IMBRUVICA®, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous
`history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop
`arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed.
`Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of
`IMBRUVICA® treatment and follow dose modification guidelines.
`
`Hypertension - Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA® with a
`median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or
`hypertension that is not adequately controlled after starting IMBRUVICA®. Adjust existing antihypertensive
`medications and/or initiate antihypertensive treatment as appropriate.
`Second Primary Malignancies - Other malignancies (range, 5% to 16%) including non-skin carcinomas (range,
`1% to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy
`was non-melanoma skin cancer (range, 4% to 13%).
`
`Tumor Lysis Syndrome - Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy.
`Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and
`treat as appropriate.
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`AbbVie Announces Fourth Breakthrough Therapy Designation Granted by the U.S. Food and Drug Administration (FDA) for Ibrutinib (IM…
`11/26/2019
`Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to
`a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA® and for 1 month after
`cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this
`drug, the patient should be apprised of the potential hazard to a fetus.
`ADVERSE REACTIONS
`
`The most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were
`neutropenia** (64%), thrombocytopenia** (63%), diarrhea (43%), anemia**(41%), musculoskeletal pain (30%),
`rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia 21%).
`
`**Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin
`decreased).
`
`The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia
`(7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).
`
`Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.
`
`Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most
`frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and
`neutropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.
`DRUG INTERACTIONS
`CYP3A Inhibitors - Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A
`inhibitor must be used, reduce the IMBRUVICA® dose.
`CYP3A Inducers - Avoid coadministration with strong CYP3A inducers.
`SPECIFIC POPULATIONS
`Hepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment. In patients
`with mild impairment, reduce IMBRUVICA® dose.
`
`Please see Full Prescribing Information:
`https://www.imbruvica.com/docs/librariesprovider7/default-document-library/prescribing_information.pdf.
`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 (http://www.abbvie.com/) . Follow @abbvie
`(http://twitter.com/abbvie) on Twitter or view careers on our Facebook (http://www.facebook.com/abbviecareers) or LinkedIn
`(http://www.linkedin.com/company/abbvie) 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
`
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`AbbVie Announces Fourth Breakthrough Therapy Designation Granted by the U.S. Food and Drug Administration (FDA) for Ibrutinib (IM…
`11/26/2019
`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
`
`[1] MedlinePlus, U.S. National Library of Medicine. Graft-versus-host-disease. Available
`from: http://www.nlm.nih.gov/medlineplus/ency/article/001309.htm (http://www.nlm.nih.gov/medlineplus/ency/article/001309.htm)
`. Accessed March 2016.
`
`[2] National Cancer Institute. NCI Dictionary of Cancer Terms. Available from:
`http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45922
`(http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45922) . Accessed June 2016.
`
`[3] Fred Hutchinson Cancer Research Center, Graft-vs.-Host-Disease. Available from:
`https://www.fredhutch.org/en/treatment/long-term-follow-up/FAQs/gvhd.html#2. Accessed June 2016.
`
`[4] U.S. Food and Drug Administration, Fact Sheet: Breakthrough Therapies. Available from:
`http://www.fda.gov/RegulatoryInformation/Legislation/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm
`(http://www.fda.gov/RegulatoryInformation/Legislation/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm) . Accessed June
`2016.
`
`[5] U.S. Food and Drug Administration. Developing Products for Rare Diseases & Conditions. Available from:
`http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm
`(http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm) . Accessed June 2016.
`
`[6] IMBRUVICA US Prescribing Information, May 2016.
`
`[7] Genetics Home Reference. Isolated growth hormone deficiency. Available
`from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency (http://ghr.nlm.nih.gov/condition/isolated-growth-
`hormone-deficiency) . Accessed May 2016.
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`SOURCE AbbVie
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