Janssen R&D To Present Data From Six Compounds Including Daratumumab And Ibrutinib At The 2016 ASCO Annual Meeting

RARITAN, N.J., May 18, 2016 /PRNewswire/ -- At the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting, Janssen Research & Development, LLC will present new data for both approved and investigational oncology and cardiovascular compounds, spanning 10 disease areas. Sixteen company-sponsored abstracts have been accepted for presentation, including for daratumumab, ibrutinib, abiraterone acetate, trabectedin, rivaroxaban and apalutamide. Most notably, Phase 3 data for the immunotherapy daratumumab in combination with standard therapy have been selected for inclusion in the Plenary Session on Sunday, June 5^th and will be featured in the ASCO Press Program.

"We are bringing to life medicines that may help to reshape the future of cancer treatment and these data show the paradigm-changing potential of both new and mature compounds in our portfolio," said Peter F. Lebowitz, M.D., Ph.D., Oncology Therapeutic Area Head, Janssen Research & Development. "We are only beginning to unlock the full potential of our therapies and we will continue to explore areas where our compounds may benefit patients in need, especially those with hard-to-treat cancers with limited treatment options."

Key data presentations from our oncology pipeline, include:

• daratumumab: Findings from the CASTOR (MMY3004) trial will provide the first look at Phase 3 data assessing the activity of daratumumab in combination with bortezomib and dexamethasone in multiple myeloma patients with at least one prior line of therapy. These pivotal data will serve as the basis for potential regulatory submissions in the U.S. and EU later this year (Abstract LBA4).
  • These data will be featured in an ASCO Press Briefing from 8:00 9:00 a.m. CDT and will be presented in the Plenary Session from 3:10 3:25 p.m. CDT on Sunday, June 5^th.
• ibrutinib: Two-year follow-up data from the Phase 3 HELIOS (CLL3001) study will provide an in-depth look into the use of ibrutinib as a combination therapy in relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). These data were included in the May 9^th update to the ibrutinib U.S. Prescribing Information (Abstract 7525). Separately, an analysis of the Phase 3 RESONATE^TM (PCYC-1112) and RESONATE^TM-2 (PCYC-1115) trials will uncover additional information specific to outcomes in CLL/SLL patients based on when they initiate therapy (Abstract 7520).
  • These data will be presented in a Poster Session from 8:00 11:30 a.m. CDT on Monday, June 6^th.
• ibrutinib: Phase 3 data from the RAY (MCL3001) study will provide insights into the mechanisms of primary and acquired resistance in previously treated mantle cell lymphoma (MCL), for which ibrutinib is currently approved in patients who have received at least one prior therapy (Abstract 7570).
  • These data will be presented in a Poster Session from 8:00 11:30 a.m. CDT on Monday, June 6^th.
• abiraterone acetate: A safety and efficacy update from the Phase 2 IMAAGEN (Impact of Abiraterone Acetate in Prostate-Specific Antigen) trial will highlight secondary endpoint results on the use of abiraterone acetate plus prednisone in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) (Abstract 5061).
  • These data will be presented in a Poster Session from 1:00 4:30 p.m. CDT on Saturday, June 4^th.

A full list of company-sponsored abstracts to be presented at the meeting follows below:

About DARZALEX^® (daratumumab)
DARZALEX^® (daratumumab) injection for intravenous use is the first CD38-directed monoclonal antibody (mAb) approved anywhere in the world.¹ CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.² Daratumumab is believed to induce tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.^1,3,4 Daratumumab is also believed to induce tumor cell death through immunomodulatory effects, according to a study recently presented at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH).⁵ Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma. DARZALEX is the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.¹

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX. DARZALEX is commercialized in the U.S. by Janssen Biotech, Inc. For more information, visit www.DARZALEX.com.

DARZALEX^® (daratumumab) Important Safety Information
CONTRAINDICATIONS - None

WARNINGS AND PRECAUTIONS
Infusion Reactions - DARZALEX can cause severe infusion reactions. Approximately half of all patients experienced a reaction, most during the first infusion. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, and hypertension. Signs and symptoms may include respiratory symptoms, such as cough, wheezing, larynx and throat tightness and irritation, laryngeal edema, pulmonary edema, nasal congestion, and allergic rhinitis. Less common symptoms were hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills.

Pre-medicate patients with antihistamines, antipyretics and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue therapy for life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions. Patients with a history of obstructive pulmonary disorders may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with obstructive pulmonary disorders.

Interference with Serological Testing - Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Interference with Determination of Complete Response - Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Adverse Reactions - The most frequently reported adverse reactions (incidence 20%) were: fatigue, nausea, back pain, pyrexia, cough, and upper respiratory tract infection.

Serious adverse reactions were reported in 51 (33%) patients. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%).

DRUG INTERACTIONS - No drug interaction studies have been performed.

About IMBRUVICA^® (ibrutinib)
IMBRUVICA^® 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).⁶ 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.^6,7 IMBRUVICA targets and blocks BTK, inhibiting cancer cell survival and spread.⁶ For more information, visit www.IMBRUVICA.com.

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.

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 nuetropenia (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.

About ZYTIGA^® (abiraterone acetate)
ZYTIGA^® (abiraterone acetate) is indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). ZYTIGA blocks CYP17-mediated androgen production which fuels prostate cancer growth at three sources: in the testes, adrenals and the prostate tumor tissue and has proven efficacy in patients with mCRPC who have progressed on androgen deprivation therapy.

Since its first approval