• Early com­bi­na­tion data from Phase 1b/2 dose-finding study indicate poten­tial efficacy in pre­vi­ously treated patients with multiple myeloma
• This release corresponds to abstract #377

North Chicago, IL (Press Release) – Today, AbbVie (NYSE: ABBV), a global bio­pharma­ceu­tical com­pany, announced pre­lim­i­nary data from the ongoing Phase 1/2b PCYC-1119 trial suggesting that the com­bi­na­tion of ibrutinib (IMBRUVICA®) plus car­filz­o­mib with or without dexa­meth­a­sone was well tolerated in re­lapsed or refractory patients with multiple myeloma (MM), with an initial objective response rate (ORR) of 62%. These data will be presented today in an oral presentation at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL at 5:30 p.m. ET. IMBRUVICA is jointly developed and com­mer­cial­ized by Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc.

MM is a blood cancer that most commonly arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow. This year, approx­i­mately 26,850 people will be diag­nosed with the disease and about 11,240 will die.¹

"Multiple myeloma can be a very dif­fi­cult form of cancer to treat and many patients eventually relapse or become resistant to treat­ment with standard ther­a­pies," said Ajai Chari, M.D., Asso­ci­ate Pro­fessor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at the Icahn School of Medicine at Mount Sinai, New York, NY, and lead study investigator.* "These initial data are encouraging as they suggest the com­bi­na­tion of ibrutinib plus car­filz­o­mib and dexa­meth­a­sone has promising clin­i­cal poten­tial, particularly in the primarily refractory patient pop­u­la­tion who par­tic­i­pated in this study."

Thirty-nine patients were evaluable for efficacy and dem­onstrated a 62% ORR during early follow-up, with a clin­i­cal benefit rate (CBR) of 72%. Overall, the com­bi­na­tion was well tolerated, with no dose-limiting toxicities observed during the dose escalation phase.

"As we con­tinue to in­ves­ti­gate the use of ibrutinib across a number of hema­to­logic malig­nan­cies, multiple myeloma remains an area of great clin­i­cal need," said Thorsten Graef, M.D., Ph.D., Head of Hematology & Global Medical Safety at Pharmacyclics. "Many of these patients eventually relapse when treated with other traditional ther­a­pies, so new options are greatly needed. We are hopeful ibrutinib may help answer the call for new alter­na­tives and look forward to continuing to follow its promising progress for the treat­ment of this disease."

The ongoing, multi­center, dose-escalation Phase 1/2b study eval­u­ated the safety and efficacy of ibrutinib in com­bi­na­tion with car­filz­o­mib with or without dexa­meth­a­sone in 40 re­lapsed or refractory MM patients. Patients received the com­bi­na­tion across multiple dose levels during the Phase 1 portion, with no dose-limiting toxicities observed. Cohorts 2b (n=14; ibrutinib 560mg once daily plus car­filz­o­mib and dexa­meth­a­sone) and 3b (n=18; ibrutinib 840mg once daily plus car­filz­o­mib and dexa­meth­a­sone) was determined to be the recommended Phase 2 dose to further assess the safety and efficacy of the com­bi­na­tion. In cohort 3b, the ORR was 65% and the CBR was 76%, in­­clud­ing three very good partial responses and one stringent com­plete response.

The most common all grade non-hematologic adverse events (AEs in ≥20% of patients) across all cohorts in this study were diarrhea, con­sti­pa­tion, fatigue, cough and nausea. Grade 3 or greater hema­to­logic AEs (≥10% of patients) in­cluded hyper­tension, anemia, pneu­monia, thrombo­cytopenia, diarrhea and fatigue. In addi­tion, 12 patients dis­con­tinued treat­ment due to progressive disease, eight dis­con­tinued due to an AE and nine dis­con­tinued due to investigator or patient de­ci­sion.

About IMBRUVICA

IMBRUVICA is cur­rently approved for the treat­ment of patients with chronic lym­pho­cytic leukemia (CLL) who have received at least one prior ther­apy, CLL patients who have del 17p and patients with Waldenström's macroglobulinemia.² IMBRUVICA is also approved for the treat­ment of patients with mantle cell lym­phoma (MCL) who have received at least one prior ther­apy. 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.²

IMBRUVICA is a first-in-class, oral, once-daily ther­apy that inhibits a protein called Bruton's tyrosine kinase (BTK).2 IMBRUVICA was one of the first medicines to receive a U.S. FDA approval after being granted a Break­through Therapy Desig­na­tion, and IMBRUVICA is one of the few ther­a­pies to receive three separate desig­na­tions.

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.^2,3 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread un­con­trol­lably.²

IMBRUVICA is being studied alone and in com­bi­na­tion with other treat­ments in several blood cancers. More than 6,100 patients have been treated in clin­i­cal trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 16 Phase 3 trials have been ini­ti­ated with IMBRUVICA and 67 trials are registered on www.clinicaltrials.gov.

To learn more about the medical terminology used in this news release, please visit http://stedmansonline.com/.

INDICATIONS

IMBRUVICA is indicated to treat people with:

• Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
• Chronic lymphocytic leukemia (CLL) with 17p deletion
• Waldenström's macroglobulinemia
• Mantle cell lymphoma (MCL) who have received at least one prior therapy – accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

Patients taking IMBRUVICA for CLL or WM should take 420 mg taken orally once daily (or three 140 mg capsules once daily).

Patients taking IMBRUVICA for MCL should take 560 mg taken orally once daily (or four 140 mg capsules once daily).

Capsules should be swallowed whole with a glass of water. Do not open, break or chew the capsules.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (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. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and non-fatal in­fec­tions have occurred with IMBRUVICA® ther­apy. Grade 3 or greater in­fec­tions occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA®. Monitor patients for fever and in­fec­tions and eval­u­ate promptly.

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%) occurred in patients treated with 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, acute in­fec­tions, and a pre­vi­ous history of atrial fibrillation. Periodically monitor patients clin­i­cally for atrial fibrillation. Patients who develop arrhythmic symp­toms (e.g., palpitations, lightheadedness) or new-onset dyspnea should have an ECG per­formed. If atrial fibrillation persists, con­sider the risks and benefits of IMBRUVICA® treat­ment and dose modification.

Second Primary Malignancies - Other malig­nan­cies (range, 5 to 14%) in­­clud­ing non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA®. The most frequent second pri­mary malig­nan­cy was non-melanoma skin cancer (range, 4 to 11%).

Tumor Lysis Syndrome - Tumor lysis syn­drome has been reported with IMBRUVICA® ther­apy. Monitor patients closely and take appro­pri­ate precautions in patients at risk for tumor lysis syn­drome (e.g., high tumor burden).

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®. 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 (≥25%) in patients with B-cell malig­nan­cies (MCL, CLL, WM) were thrombo­cytopenia* (57%, 52%, 43%), neu­tro­penia* (47%, 51%, 44%), diarrhea (51%, 48%, 37%), anemia* (41%, 36%, 13%), fatigue (41%, 28%, 21%), mus­cu­lo­skel­etal pain (37%, 28%**, NA***), bruising (30%, 12%**, 16%**), nausea (31%, 26%, 21%), upper res­pira­tory tract in­fec­tion (34%, 16%, 19%), and rash (25%, 24%**, 22%**).

*Based on adverse reac­tions and/or laboratory mea­sure­ments (noted as platelets, neu­tro­phils, or hemoglobin de­creased).

**Includes multiple ADR terms.
***Not appli­­cable; no asso­ci­ated ADRs.

The most common Grade 3 or 4 non-hematological 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 events.

Approximately 5% (CLL), 9% (MCL), and 6% (WM) of patients dis­con­tinued due to adverse events. Most frequent adverse events leading to dis­con­tinu­a­tion were in­fec­tions, subdural hematomas, and diarrhea in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors - Avoid co-administration with strong and mod­er­ate CYP3A inhibitors. If a mod­er­ate CYP3A inhibitor must be used, reduce the IMBRUVICA® dose.

CYP3A Inducers - Avoid co-administration 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: http://www.imbruvica.com/downloads/Prescribing_Information.pdf.

About Pharmacyclics, An AbbVie Company

Pharmacyclics, a wholly-owned sub­sid­i­ary of AbbVie (NYSE: ABBV), is focused on devel­op­ing and com­mer­cial­iz­ing inno­va­tive small-molecule drugs for the treat­ment of cancer and immune-mediated diseases. Pharmacyclics' mission is to develop and com­mer­cial­ize novel ther­a­pies intended to im­prove quality of life, in­­crease duration of life and resolve serious unmet medical needs.

Pharmacyclics markets IMBRUVICA and has two prod­uct can­di­dates in clin­i­cal devel­op­ment and several pre­clin­i­cal molecules in lead optimization. Pharmacyclics is committed to high standards of ethics, scientific rigor and operational efficiency as it moves each of these pro­grams to­ward com­mer­cial­iza­tion. To learn more, please visit www.pharmacyclics.com.

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 inno­va­t 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, the likelihood that the trans­­action is consummated, the ex­pec­ted benefits of the trans­­action, 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.

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

IMBRUVICA is a registered trademark of Pharmacyclics LLC.

1. American Cancer Society. What are the key statistics about multiple myeloma. Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed December 2015.
2. IMBRUVICA Prescribing Information, January 2015
3. Genetics Home Reference. Isolated growth hormone deficiency. Available at: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed December 2015.

Source: AbbVie.