ASH 2017: Janssen to Present 40 Abstracts, Including 8 Oral Presentations, With New Data on DARZALEX (Daratumumab), IMBRUVICA (Ibrutinib) and Other Compounds From Robust Portfolio
- Includes early data evaluating the subcutaneous delivery of DARZALEX in relapsed or refractory multiple myeloma and new Phase 2 data for single-agent DARZALEX in smoldering multiple myeloma
- Updated data for the Phase 3 CASTOR and POLLUX studies on the longer-term clinical efficacy of DARZALEX combination therapy in previously-treated patients with multiple myeloma
- Additionally, 3.5-year follow-up data for IMBRUVICA in relapsed or refractory mantle cell lymphoma showed clinical outcomes were best for patients who were treated after one prior therapy, with a median progression-free survival of 33 months
- XARELTO safety and efficacy results in cancer-associated VTE to be presented
RARITAN, N.J., Nov. 1, 2017 /PRNewswire/ -- New data for the immunotherapy DARZALEX®(daratumumab) and first-in-class BTK inhibitor IMBRUVICA® (ibrutinib) are among eight oral presentations from Janssen Research & Development LLC, to be featured at the 59th American Society of Hematology (ASH) Annual Meeting & Exhibition taking place December 9-12, in Atlanta, GA. In total, 40 company-sponsored abstracts for both approved and investigational oncology and cardiovascular compounds have been accepted for presentation. In addition to IMBRUVICA and DARZALEX, data from studies of oral anticoagulant XARELTO® (rivaroxaban) and investigational compound imetelstat, and more than 20 investigator-initiated studies for all of these compounds, will be presented.
"This year's ASH meeting promises important updates for approved and investigational compounds across our hematology portfolio," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head of Oncology, Janssen Research & Development. "Data showing long-term outcomes for DARZALEX and IMBRUVICA, as well as initial compelling results for these therapies and new pipeline products, show our strong focus on developing transformational therapies and our unwavering commitment to people living with blood cancers."
Key company-sponsored data presentations include:
- DARZALEX: Early data from the Phase 1b PAVO study will be presented on the tolerability of the subcutaneous delivery of DARZALEX co-formulated with recombinant human hyaluronidase PH20 in patients with relapsed or refractory multiple myeloma. Updated safety, efficacy and pharmacokinetic data for this new investigational delivery method for DARZALEX will be presented at the meeting.
- The Phase 1b data will be presented as an oral presentation at 5:15 p.m. ET on Monday, December 11 (Abstract #838).
- DARZALEX: The first look at results from the Phase 2 CENTAURUS trial assessing DARZALEX monotherapy for patients with intermediate or high-risk smoldering multiple myeloma will be presented. Smoldering multiple myeloma is an asymptomatic precursor stage to multiple myeloma, where early intervention to delay or prevent the progression to active disease could benefit patients. These results will serve as the basis of a Phase 3 study, with enrollment initiating later this year.
- The Phase 2 data will be presented as an oral presentation at 5:45 p.m. ET on Sunday, December 10 (Abstract #510).
- DARZALEX: Updated analyses from two pivotal trials will be presented. Long-term progression-free survival (PFS) data from the Phase 3 POLLUX trial, which assessed DARZALEX in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy, will be presented. Additionally, data from the Phase 3 CASTOR clinical trial will provide a first look at overall survival for DARZALEX in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
- The updated POLLUX data will be presented as an oral presentation at 2:45 p.m. ET on Monday, December 11 (Abstract #739).
- The updated CASTOR data will be presented as a poster presentation from 5:30 – 7:30 p.m. ET on Saturday, December 9 (Abstract #1852).
- IMBRUVICA: A pooled analysis of 3.5-year follow-up data from Phase 2 and Phase 3 studies further supports PFS of the first-in-class BTK inhibitor IMBRUVICA in patients with relapsed or refractory Mantle Cell Lymphoma (MCL).
- The pooled analysis will be presented as an oral presentation at 12:00 p.m. ET on Saturday, December 9 (Abstract #151).
- IMBRUVICA: Results from a Phase 1/2a study evaluating the safety and efficacy of IMBRUVICA in combination with nivolumab in patients with relapsed or refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia will be presented for the first time.
- The Phase 1/2a data will be presented as an oral presentation at 5:30 p.m. ET on Monday, December 11 (Abstract #833).
- Imetelstat: Data from the first 32 patients enrolled in Part 1 of an ongoing Phase 2/3 clinical trial of imetelstat in patients with transfusion-dependent anemia due to low or intermediate 1 risk myelodysplastic syndromes (MDS) that is not associated with the deletion 5q cytogenetic abnormality (del[5q]) and who are refractory/resistant to treatment with an erythropoiesis-stimulating agent (ESA) will be presented.
- The Phase 2/3 study will be presented as a poster presentation from 6:00 – 8:00 p.m. ETon Monday, December 11 (Abstract #4256).
- Imetelstat: Integrated molecular analysis will identify replicative stress as a sensitizer to imetelstat in Acute Myeloid Leukemia (AML) cells.
- The analysis will be presented as an oral presentation at 5:45 p.m. ET on Monday, December 11 (Abstract #798).
- XARELTO: Data will be presented evaluating XARELTO for the treatment of venous thromboembolism (VTE), including economic findings from the EINSTEIN CHOICE study and efficacy and safety results in people with cancer-associated VTE. VTE is the second leading cause of death in people with active cancer.
- EINSTEIN CHOICE data will be presented as an oral presentation at 2:15 p.m. ET on Saturday, December 9 (Abstract #218).
- Cancer-associated VTE data will be presented as an oral presentation at 10:30 a.m. ET on Monday, December 11 (Abstract #625).
A full list of company-sponsored abstracts to be presented at the meeting follows below:
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Abstract No. |
Title |
Date/Time |
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DARZALEX |
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Oral Presentations |
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Abstract #510 |
Daratumumab monotherapy for patients with |
Oral Session Sunday, December 10 5:45 p.m. ET
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Abstract #838 |
Subcutaneous Delivery of Daratumumab in Patients |
Oral Session Monday, December 11 5:15 p.m. ET |
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Abstract #739 |
Daratumumab, Lenalidomide, and Dexamethasone |
Oral Session Monday, December 11 2:45 p.m. ET
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Poster Presentations |
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Abstract #1883 |
Daratumumab, Lenalidomide, and Dexamethasone |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #1852 |
Daratumumab, bortezomib, and dexamethasone |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #1828 |
Daratumumab in Combination with Lenalidomide |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #1869 |
Daratumumab in Combination with Carfilzomib and |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #2113 |
Treatment Patterns and Survival Outcomes in Latin |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #1879 |
Interim Safety Analysis of a Phase 2 Randomized |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #1824 |
Daratumumab in Combination with Pomalidomide |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #1839 |
Results of an Interim Safety Analysis of a Phase 2 |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #3107 |
Safety and Efficacy of Daratumumab Monotherapy |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #3100 |
Daratumumab (DARA) in Combination with |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #3124 |
Daratumumab in Combination with Lenalidomide |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #3093 |
Evaluation of Efficacy Outcomes among Relapsed/ |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #3094 |
Comparison of Overall Survival Associated with |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #3145 |
Daratumumab, Bortezomib, and Dexamethasone |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #3805 |
Proteomic profiling reveals targetable pathways in |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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IMBRUVICA |
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Oral Presentations |
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Abstract #151 |
Median 3.5-year Follow-Up of Ibrutinib Treatment in |
Oral Session Saturday, December 9 12:00 p.m. ET |
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Abstract #833 |
LYM1002: Phase 1/2A Study of Ibrutinib + |
Oral Session Monday, December 11 5:30 p.m. ET
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Poster Presentations |
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Abstract #2770 |
Comparative effectiveness of single-agent ibrutinib |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #2783 |
FL/MZL: Systematic literature review of the clinical |
Poster Session Sunday, December 10 6:00 – 8:00 p.m.ET |
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Abstract #4303 |
A validated risk model for overall survival in |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET
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Imetelstat |
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Oral Presentations |
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Abstract #798 |
Integrated Molecular Analysis Identifies Replicative |
Oral Session Monday, December 11 5:45 p.m. ET |
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Poster Presentations |
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Abstract #1654 |
Imetelstat, a Telomerase Inhibitor, Is Capable of |
Poster Session Saturday, December 9 5:30 – 7:30 p.m. ET |
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Abstract #2860 |
Telomerase Inhibition Impairs Self-renewal of b- |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #4256 |
Efficacy and Safety of Imetelstat in RBC |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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XARELTO |
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Oral Presentations |
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Abstract #218 |
Healthcare Cost Impact of Continued |
Oral Session Saturday, December 9 2:15 p.m. ET |
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Abstract #625 |
Anticoagulation Therapy in Cancer Patients at Risk |
Oral Session |
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Poster Presentations |
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Abstract #2142 |
Does Treatment Satisfaction Influence Adherence |
Poster Session Saturday, December 9 5:30 - 7:30 p.m. ET |
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Abstract #1107 |
The Effect of Rivaroxaban Exposure and Clinical |
Poster Session Saturday, December 9 5:30 - 7:30 p.m. ET |
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Abstract #1104 |
The Effects of Rivaroxaban Exposure and of |
Poster Session Saturday, December 9 5:30 - 7:30 p.m. ET |
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Abstract #2386 |
A Pooled Analysis of the XALIA and XALIA-LEA |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #2393 |
Effectiveness and Safety of Rivaroxaban vs. |
Poster Session Sunday, December 10 6:00 – 8:00 p.m. ET |
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Abstract #4727 |
Patient Preferences Regarding Non-Vitamin K |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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Abstract #4631 |
VTE Recurrence and Safety of Anticoagulants |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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Abstract #4640 |
Healthcare Costs Associated with Venous |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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Abstract #3717 |
Effectiveness and Safety of Rivaroxaban in |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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Abstract #3718 |
Effects of Rivaroxaban Exposure and of Clinical |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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Abstract #4726 |
Real-World Adherence to Non-Vitamin K |
Poster Session Monday, December 11 6:00 – 8:00 p.m. ET |
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About DARZALEX Injection, for Intravenous Infusion
DARZALEX (daratumumab) injection for intravenous use is the first CD38-directed antibody approved anywhere in the world.[1] CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.[2] DARZALEX is believed to induce tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated 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.[3] A subset of myeloid derived suppressor cells (MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by DARZALEX.3DARZALEX is being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.[4],[5],[6],[7],[8]Additional studies are ongoing or planned to assess its potential for a solid tumor indication and in other malignant and pre-malignant diseases in which CD38 is expressed, such as smoldering myeloma.[9],[10],[11] DARZALEX was the first CD38-directed antibody to receive regulatory approval to treat relapsed or refractory multiple myeloma.[12]
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.[13],[14] Refractory cancer occurs when a patient's disease is resistant to treatment or in the case of multiple myeloma, patients progress within 60 days of their last therapy.[15],[16] Relapsed cancer means the disease has returned after a period of initial, partial or complete remission.[17] Globally, it is estimated that 124,225 people were diagnosed and 87,084 died from the disease in 2015.[18],[19] While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.[20]
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, hypertension, laryngeal edema and pulmonary edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension.
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 following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.
Interference with Serological Testing - Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect 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.
Neutropenia - DARZALEX may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. DARZALEX dose delay may be required to allow recovery of neutrophils. No dose reduction of DARZALEX is recommended. Consider supportive care with growth factors.
Thrombocytopenia - DARZALEX may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. DARZALEX dose delay may be required to allow recovery of platelets. No dose reduction of DARZALEX is recommended. Consider supportive care with transfusions.
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 – In patients who received DARZALEX in combination with lenalidomide and dexamethasone, the most frequently reported adverse reactions (incidence ≥20%) were: neutropenia (92%), thrombocytopenia (73%), upper respiratory tract infection (65%), infusion reactions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%) and pyrexia (20%). The overall incidence of serious adverse reactions was 49%. Serious adverse reactions were pneumonia (12%), upper respiratory tract infection (7%), influenza (3%) and pyrexia (3%).
In patients who received DARZALEX in combination with bortezomib and dexamethasone, the most frequently reported adverse reactions (incidence ≥20%) were: thrombocytopenia (90%), neutropenia (58%), peripheral sensory neuropathy (47%), infusion reactions (45%), upper respiratory tract infection (44%), diarrhea (32%), cough (27%), peripheral edema (22%), and dyspnea (21%). The overall incidence of serious adverse reactions was 42%. Serious adverse reactions were upper respiratory tract infection (5%), diarrhea (2%) and atrial fibrillation (2%).
In patients who received DARZALEX as monotherapy, the most frequently reported adverse reactions (incidence ≥20%) were: neutropenia (60%), thrombocytopenia (48%), infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper respiratory tract infection (20%). 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%).
In patients who received DARZALEX in combination with pomalidomide and dexamethasone, the most frequent adverse reactions (>20%) were infusion reactions (50%), diarrhea (38%), constipation (33%), nausea (30%), vomiting (21%), fatigue (50%), pyrexia (25%), upper respiratory tract infection (50%), muscle spasms (26%), back pain (25%), arthralgia (22%), dizziness (21%), insomnia (23%), cough (43%) and dyspnea (33%). The overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients included pneumonia (7%).
DRUG INTERACTIONS
Effect of Other Drugs on daratumumab: The coadministration of lenalidomide, pomalidomide or bortezomib with DARZALEX did not affect the pharmacokinetics of daratumumab.
Effect of Daratumumab on Other Drugs: The coadministration of DARZALEX with bortezomib did not affect the pharmacokinetics of bortezomib.
About IMBRUVICA
IMBRUVICA (ibrutinib) 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 protein called Bruton's tyrosine kinase (BTK). 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.[21] IMBRUVICA targets and blocks BTK, inhibiting the survival and spread of cancer cells, and impacting signaling associated with other serious conditions. For more information, visit www.IMBRUVICA.com.
Additional Information about IMBRUVICA®
INDICATIONS
IMBRUVICA® is indicated to treat adults with:
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion
- Waldenström's macroglobulinemia (WM)
- Mantle cell lymphoma (MCL) patients 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 and description of clinical benefit in a confirmatory trial.
- Marginal zone lymphoma (MZL) patients who require systemic therapy and have received at least one prior anti-CD20-based therapy
- Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
- Chronic Graft-Versus-Host-Disease (cGVHD) patients who failed one or more lines of systemic therapy
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 post-surgery depending upon the type of surgery and the risk of bleeding.
Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA®. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.
Monitor and evaluate patients for fever and infections and treat appropriately.
Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 13%) based on laboratory measurements occurred in patients with B-cell malignancies 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 (e.g., 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 anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.
Second Primary Malignancies: Other malignancies (range, 3 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, 2 to 13%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA®therapy. Assess the baseline risk (e.g., 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. Advise men to avoid fathering a child during the same time period.
ADVERSE REACTIONS
B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (62%), neutropenia (61%), diarrhea (43%), anemia (41%), musculoskeletal pain (30%), rash (30%), bruising (30%), nausea (29%), fatigue (29%), hemorrhage (22%), and pyrexia (21%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%), thrombocytopenia (16%), and pneumonia (10%).
Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9 % (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions.
cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%), muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%), and pneumonia (21%).
The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%), pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).
Twenty-four percent of patients receiving IMBRUVICA® in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.
DRUG INTERACTIONS
CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.
CYP3A Inhibitors: Dose adjustment may be recommended.
SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® 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/prescribing-information.
About Imetelstat
Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Imetelstat has not been approved for marketing by any regulatory authority. Janssen entered into an exclusive worldwide license and collaboration agreement with Geron Corporation (Nasdaq: GERN) in November 2014 to develop and commercialize imetelstat, an investigational telomerase inhibitor.
WHAT IS XARELTO®?
XARELTO® is a prescription medicine used to reduce the risk of stroke and blood clots in people with atrial fibrillation, not caused by a heart valve problem. For patients currently well managed on warfarin, there is limited information on how XARELTO® and warfarin compare in reducing the risk of stroke.
XARELTO® is also a prescription medicine used to treat deep vein thrombosis (DVT) and pulmonary embolism (PE), and to reduce the risk of blood clots happening again in people who continue to be at risk for DVT or PE after receiving treatment for blood clots for at least 6 months.
XARELTO® is also a prescription medicine used to reduce the risk of forming a blood clot in the legs and lungs of people who have just had knee or hip replacement surgery.
IMPORTANT SAFETY INFORMATION
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT XARELTO®?
- For people taking XARELTO® for atrial fibrillation:
People with atrial fibrillation (an irregular heart beat) are at an increased risk of forming a blood clot in the heart, which can travel to the brain, causing a stroke, or to other parts of the body. XARELTO® lowers your chance of having a stroke by helping to prevent clots from forming. If you stop taking XARELTO®, you may have increased risk of forming a clot in your blood.
Do not stop taking XARELTO® without talking to the doctor who prescribes it for you. Stopping XARELTO® increases your risk of having a stroke.
If you have to stop taking XARELTO®, your doctor may prescribe another blood thinner medicine to prevent a blood clot from forming. - XARELTO® can cause bleeding, which can be serious, and rarely may lead to death. This is because XARELTO® is a blood thinner medicine (anticoagulant) that reduces blood clotting. While you take XARELTO® you are likely to bruise more easily, and it may take longer for bleeding to stop.
You may have a higher risk of bleeding if you take XARELTO® and take other medicines that increase your risk of bleeding, including:- Aspirin or aspirin-containing products
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Warfarin sodium (Coumadin®, Jantoven®)
- Any medicine that contains heparin
- Clopidogrel (Plavix®)
- Selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)
- Other medicines to prevent or treat blood clots
Tell your doctor if you take any of these medicines. Ask your doctor or pharmacist if you are not sure if your medicine is one listed above.
Call your doctor or get medical help right away if you develop any of these signs or symptoms of bleeding:
- Unexpected bleeding or bleeding that lasts a long time, such as:
- Nosebleeds that happen often
- Unusual bleeding from gums
- Menstrual bleeding that is heavier than normal, or vaginal bleeding
- Bleeding that is severe or you cannot control
- Red, pink, or brown urine
- Bright red or black stools (looks like tar)
- Cough up blood or blood clots
- Vomit blood or your vomit looks like "coffee grounds"
- Headaches, feeling dizzy or weak
- Pain, swelling, or new drainage at wound sites
- Spinal or epidural blood clots (hematoma): People who take a blood thinner medicine like XARELTO®, and have medicine injected into their spinal and epidural area, or have a spinal puncture, have a risk of forming a blood clot that can cause long-term or permanent loss of the ability to move (paralysis). Your risk of developing a spinal or epidural blood clot is higher if:
- A thin tube called an epidural catheter is placed in your back to give you certain medicine
- You take NSAIDs or a medicine to prevent blood from clotting
- You have a history of difficult or repeated epidural or spinal punctures
- You have a history of problems with your spine or have had surgery on your spine
If you take XARELTO® and receive spinal anesthesia or have a spinal puncture, your doctor should watch you closely for symptoms of spinal or epidural blood clots. Tell your doctor right away if you have back pain, tingling, numbness, muscle weakness (especially in your legs and feet), or loss of control of the bowels or bladder (incontinence).
- XARELTO® is not for people with artificial heart valves.
Do not take XARELTO® if you: - Currently have certain types of abnormal bleeding. Talk to your doctor before taking XARELTO® if you currently have unusual bleeding.
- Are allergic to rivaroxaban or any of the ingredients of XARELTO®.
Before taking XARELTO®, tell your doctor about all your medical conditions, including if you: - Have ever had bleeding problems
- Have liver or kidney problems
- Are pregnant or plan to become pregnant. It is not known if XARELTO® will harm your unborn baby.
- Tell your doctor right away if you become pregnant during treatment with XARELTO®. Taking XARELTO® while you are pregnant may increase the risk of bleeding in you or in your unborn baby.
- If you take XARELTO® during pregnancy, tell your doctor right away if you have any signs or symptoms of bleeding or blood loss. See "What is the most important information I should know about XARELTO®?" for signs and symptoms of bleeding.
- Are breastfeeding or plan to breastfeed. XARELTO® may pass into your breast milk. You and your doctor should decide if you will take XARELTO® or breastfeed.
Tell all of your doctors and dentists that you are taking XARELTO®. They should talk to the doctor who prescribed XARELTO® for you before you have any surgery, medical or dental procedure.
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some of your other medicines may affect the way XARELTO® works. Certain medicines may increase your risk of bleeding. See "What is the most important information I should know about XARELTO®?"
HOW SHOULD I TAKE XARELTO®?
- Take XARELTO® exactly as prescribed by your doctor.
- Do not change your dose or stop taking XARELTO® unless your doctor tells you to.
- Your doctor may change your dose if needed.
- If you take XARELTO® for:
- Atrial Fibrillation:
- Take XARELTO® 1 time a day with your evening meal.
- If you miss a dose of XARELTO®, take it as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- Blood clots in the veins of your legs or lungs:
- Take XARELTO® 1 or 2 times a day as prescribed by your doctor.
- For the 15-mg and 20-mg doses, XARELTO® should be taken with food.
- For the 10-mg dose, XARELTO® may be taken with or without food.
- Take your XARELTO® dose(s) at the same time each day.
- If you miss a dose:
- If you take the 15-mg dose of XARELTO® 2 times a day (a total of 30 mg of XARELTO® in 1 day): Take XARELTO® as soon as you remember on the same day. You may take 2 doses at the same time to make up for the missed dose. Take your next dose at your regularly scheduled time.
- If you take XARELTO® 1 time a day: Take XARELTO® as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- Hip or knee replacement surgery:
- Take XARELTO® 1 time a day with or without food.
- If you miss a dose of XARELTO®, take it as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- Atrial Fibrillation:
- If you have difficulty swallowing the XARELTO® tablet whole, talk to your doctor about other ways to take XARELTO®.
- Your doctor will decide how long you should take XARELTO®.
- Your doctor may stop XARELTO® for a short time before any surgery, medical or dental procedure. Your doctor will tell you when to start taking XARELTO® again after your surgery or procedure.
- Do not run out of XARELTO®. Refill your prescription for XARELTO® before you run out. When leaving the hospital following a hip or knee replacement, be sure that you have XARELTO®available to avoid missing any doses.
- If you take too much XARELTO®, go to the nearest hospital emergency room or call your doctor right away.
WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO®?
- See "What is the most important information I should know about XARELTO®?"
Call your doctor for medical advice about side effects. You are also encouraged to report side effects to the FDA: visit http://www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Janssen Pharmaceuticals, Inc., at 1-800-JANSSEN (1-800-526-7736).
Please see full Prescribing Information, including Boxed Warnings, and Medication Guide.
Trademarks are those of their respective owners.
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding the continued study and development of DARZALEX® (daratumumab), IMBRUVICA® (ibrutinib) and XARELTO® (rivaroxaban), The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges inherent in product research and development, including uncertainty of clinical success and obtaining regulatory approvals; uncertainty of commercial success for new products or new indications; manufacturing difficulties or delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; product efficacy or safety concerns resulting in product recalls or regulatory action; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2017, including under "Item 1A. Risk Factors," its most recently filed Quarterly Report on Form 10-Q, including in the section captioned "Cautionary Note Regarding Forward-Looking Statements," and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
1 Janssen Biotech, Inc. "Janssen Submits Application to U.S. FDA to Expand Indication for Daratumumab (DARZALEX®)." Issued August 17, 2016.
2 Fedele G et al. CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFNγ Cytokines and Proliferation. Mediators Inflamm. 2013;2013:564687.
3 DARZALEX Prescribing Information, June 2017.
4 Janssen Research & Development, LLC. A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 NLM Identifier: NCT02136134.
5 Janssen Research & Development, LLC. Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 NLM Identifier: NCT02076009.
6 Janssen Research & Development, LLC. A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006&rank=2 NLM Identifier: NCT02541383.
7 Janssen Research & Development, LLC. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479.
8 Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1Identifier: NCT02252172.
9 Janssen Research & Development, LLC. "Janssen Announces the Initiation of Two Studies Evaluating Daratumumab (DARZALEX®) and Atezolizumab in Multiple Myeloma and Solid Tumor." Issued March 21, 2016.
10 Janssen Research & Development, LLC. A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02316106?term=smm2001&rank=1 Identifier: NCT02316106.
11 Janssen Research & Development, LLC. An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489?term=lym2001&rank=1 Identifier: NCT02413489.
12 Janssen Biotech, Inc. "DARZALEX (daratumumab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of multiple Myeloma." Issued November 16, 2015.
13 Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
14 American Cancer Society. "Multiple Myeloma Overview." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. May 2017.
15 National Cancer Institute. "NCI Dictionary of Cancer Terms: Refractory." Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245. Accessed November 2015.
16 Richardson, et al. "The Treatment of Relapsed and Refractory Multiple Myeloma." ASH Education Book January 1, 2007 vol. 2007 no. 1 317-323.
17 National Cancer Institute. "NCI Dictionary of Cancer Terms: Relapsed." Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866. Accessed November 2015.
18 GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of New Cancers in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute. Accessed May 2017.
19 GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of Cancer Deaths in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=1&window=1&submit=%C2%A0Execute. Accessed May 2017.
20 American Cancer Society. "How is Multiple Myeloma Diagnosed?" Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed November 2015.
21 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed April 2017.
Media Inquiries:
Satu Kaarina Glawe
Mobile: +49 172 294 6264
Megan Farina
Mobile: 1-610-724-1079
Investor Relations:
Lesley Fishman
Phone: 1-732-524-3922
U.S. Medical Inquiries:
(DARZALEX, XARELTO and imetelstat):
1-800-526-7736
(IMBRUVICA –
Pharmacyclics/AbbVie):
1-877-877-3536
SOURCE Janssen Pharmaceutical Companies