Janssen Announces Submission to U.S. FDA for New DARZALEX? (Daratumumab)-Based Combination Regimen for Patients with Relapsed/Refractory Multiple Myeloma
[caption id="attachment_9277" align="aligncenter" width="747"] Press Release[/caption]
? Application is based on positive data from the Phase 3 CANDOR study, which were presented
at the 2019 American Society of Hematology Annual Meeting
RARITAN, NJ, February 10, 2020 ? The Janssen Pharmaceutical Companies of Johnson & Johnson
announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S.
Food and Drug Administration (FDA) seeking approval of DARZALEX? (daratumumab) in
combination with Kyprolis? (carfilzomib) and dexamethasone (DKd) for relapsed/refractory multiple
myeloma. The sBLA is supported by results from the Phase 3 CANDOR study, which compared
treatment with DKd to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who
relapsed after one to three prior lines of therapy.
?While we continue to make important strides in the treatment of multiple myeloma, unfortunately
most patients will relapse at some point, so it is important that physicians have multiple treatment
options and regimens for patients,? said Craig Tendler, M.D., Vice President, Late Development and
Global Medical Affairs, Janssen Research & Development, LLC. ?The results from the CANDOR study
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support the potential benefit of this DARZALEX-based combination regimen for patients with
multiple myeloma who have relapsed from prior treatment.?
Data from the Phase 3 CANDOR study were presented as a late-breaking abstract at the 2019
American Society of Hematology (ASH) Annual Meeting.
About the CANDOR Study
CANDOR is a randomized, open-label Phase 3 study of DARZALEX? (daratumumab), carfilzomib and
dexamethasone (DKd) compared to carfilzomib and dexamethasone (Kd) alone. The study
evaluated 466 relapsed or refractory patients with multiple myeloma who had received one to three
prior lines of therapy from 120 global sites. Patients were treated until disease progression. The
primary endpoint was progression free survival (PFS), and the key secondary endpoints were overall
response rate, minimal residual disease and overall survival. PFS was defined as time from
randomization until disease progression or death from any cause.
All patients received carfilzomib as a 30-minute intravenous (IV) infusion on days 1, 2, 8, 9, 15, and
16 of each 28-day cycle (20 mg/m2 on days 1 and 2 during cycle 1 and 56 mg/m2
thereafter) and
received 40 mg dexamethasone oral or IV weekly (20 mg/m2
for patients aged >75 years). In the
treatment arm, DARZALEX? 8 mg/kg was administered IV on days 1 and 2 of cycle 1 and 16 mg/kg
IV once weekly for the remaining doses of the first two cycles, then every two weeks for four cycles
(cycles 3 to 6), and every four weeks thereafter.
CANDOR is an Amgen-sponsored study and is co-funded by Janssen Research & Development, LLC.
For more information about this trial, please visit www.clinicaltrials.gov under trial identification
number NCT03158688.
About DARZALEX? (daratumumab)
DARZALEX? (daratumumab), the first monoclonal antibody for multiple myeloma approved
anywhere in the world, is the only CD38-directed antibody approved to treat multiple myeloma.1
CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of
the stage of disease.2 DARZALEX? binds to CD38 and inhibits tumor cell growth causing myeloma
cell death.3 DARZALEX? may also have an effect on normal cells.3 DARZALEX? 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.3,4,5,6,7,8,9,10 Additional studies are ongoing or
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planned to assess its potential in other malignant and pre-malignant hematologic diseases in which
CD38 is expressed, such as smoldering myeloma.11,12
In the U.S., DARZALEX? received initial FDA approval in November 2015 as a monotherapy for
patients with multiple myeloma who have received at least three prior lines of therapy, including a
proteasome inhibitor (PI) and an immunomodulatory agent, or who are double refractory to a PI
and an immunomodulatory agent.13 DARZALEX? received add
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CONTRAINDICATIONS
DARZALEX? (daratumumab) is contraindicated in patients with a history of severe hypersensitivity
(e.g., anaphylactic reactions) to daratumumab or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Infusion Reactions ? DARZALEX? can cause severe and/or serious infusion reactions,
including anaphylactic reactions. In clinical trials, approximately half of all patients experienced
an infusion reaction. Most infusion reactions occurred during the first infusion and were Grade 1-
2. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during
infusion or within 4 hours of completing DARZALEX?. 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 if an anaphylactic
reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care.
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
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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 and Thrombocytopenia ? DARZALEX? may increase neutropenia
and/or thrombocytopenia induced by background therapy. Monitor complete blood cell
counts periodically during treatment according to the 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
and/or platelets. No dose reduction of DARZALEX? is recommended. Consider
supportive care with growth factors for neutropenia or transfusions for
thrombocytopenia.
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 Mprotein. 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:
infusion reactions, neutropenia, thrombocytopenia, fatigue, asthenia, nausea, diarrhea,
constipation, decreased appetite, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills,
dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, bronchitis,
pneumonia, and upper respiratory tract infection.
DARZALEX? in combination with lenalidomide and dexamethasone (DRd): The most frequent
(=20%) adverse reactions for newly diagnosed or relapsed/refractory patients were, respectively,
infusion reactions (41%, 48%), diarrhea (57%, 43%), nausea (32%, 24%), fatigue (40%, 35%),
pyrexia (23%, 20%), upper respiratory tract infection (52%, 65%), muscle spasms (29%, 26%),
dyspnea (32%, 21%), and cough (30%, 30%). In newly diagnosed patients, constipation (41%),
peripheral edema (41%), back pain (34%), asthenia (32%), bronchitis (29%), pneumonia (26%),
peripheral sensory neuropathy (24%), and decreased appetite (22%) were also reported. In newly
diagnosed patients, serious adverse reactions (=2% compared to Rd) were pneumonia (15%),
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bronchitis (4%), and dehydration (2%), and treatment-emergent Grade 3-4 hematology
laboratory abnormalities (=20%) were neutropenia (56%), lymphopenia (52%), and leukopenia
(35%). In relapsed/refractory patients, serious adverse reactions (=2% compared to Rd) were
pneumonia (12%), upper respiratory tract infection (7%), influenza (3%), and pyrexia (3%),
and treatment-emergent Grade 3-4 hematology laboratory abnormalities (=20%) were
neutropenia (53%) and lymphopenia (52%).
DARZALEX? in combination with bortezomib, melphalan, and prednisone (DVMP): The most
frequently reported adverse reactions (=20%) were upper respiratory tract infection (48%),
infusion reactions (28%), and peripheral edema (21%). Serious adverse reactions (=2% compared
to the VMP arm) were pneumonia (11%), upper respiratory tract infection (5%), and pulmonary
edema (2%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities (=20%) were
lymphopenia (58%), neutropenia (44%), and thrombocytopenia (38%).
DARZALEX? in combination with bortezomib and dexamethasone (DVd): The most frequently
reported adverse reactions (=20%) were 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 (=2% compared to Vd) were upper respiratory
tract infection (5%), diarrhea (2%), and atrial fibrillation (2%). Treatment-emergent Grade 3-4
hematology laboratory abnormalities (=20%) were lymphopenia (48%) and thrombocytopenia
(47%).
DARZALEX? in combination with bortezomib, thalidomide, and dexamethasone (DVTd): The
most frequent adverse reactions (=20%) were infusion reactions (35%), nausea (30%), upper
respiratory tract infection (27%), pyrexia (26%), and bronchitis (20%). Serious adverse
reactions (=2% compared to the VTd arm) were bronchitis (DVTd 2% vs VTd <1%) and
pneumonia (DVTd 6% vs VTd 4%). Treatment-emergent Grade 3-4 hematology laboratory
abnormalities (=20%) were lymphopenia (59%), neutropenia (33%), and leukopenia (24%).
DARZALEX? in combination with pomalidomide and dexamethasone (DPd): The most frequent
adverse reactions (>20%) were fatigue (50%), infusion reactions (50%), upper respiratory tract
infection (50%), cough (43%), diarrhea (38%), constipation (33%), dyspnea (33%), nausea
(30%), muscle spasms (26%), back pain (25%), pyrexia (25%), insomnia (23%), arthralgia (22%),
dizziness (21%), and vomiting (21%). The overall incidence of serious adverse reactions was 49%.
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Serious adverse reactions reported in =5% of patients included pneumonia (7%). Treatmentemergent Grade 3-4 hematology laboratory abnormalities (=20%) were neutropenia (82%),
lymphopenia (71%), and anemia (30%).
DARZALEX? as monotherapy: The most frequently reported adverse reactions (=20%) were
infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%),
cough (21%), and upper respiratory tract infection (20%). The overall incidence of serious
adverse reactions was 33%. The most frequent serious adverse reactions were pneumonia (6%),
general physical health deterioration (3%), and pyrexia (3%). Treatment-emergent Grade 3-4
hematology laboratory abnormalities (=20%) were lymphopenia (40%) and neutropenia (20%).
Please click here to see the full Prescribing Information.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we?re creating a future where disease is a thing of the past. We?re the Pharmaceutical
Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients
everywhere by fighting sickness with science, improving access with ingenuity, and healing
hopelessness with heart. We focus on areas of medicine where we can make the biggest difference:
Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience,
Oncology, and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research &
Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of
Johnson & Johnson.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities
Litigation Reform Act of 1995 regarding DARZALEX? (daratumumab). 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, or any of the other Janssen Pharmaceutical Companies
and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and
uncertainties inherent in product research and development, including the uncertainty of clinical
success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing
difficulties and delays; competition, including technological advances, new products and patents
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attained by competitors; challenges to patents; product efficacy or safety concerns resulting in
product recalls or regulatory action; changes in behavior and spending patterns of purchasers of
health care products and services; changes to applicable laws and regulations, including global
health care reforms; and trends toward health care cost containment. A further list and descriptions
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 December 30, 2018, including in the sections captioned
?Cautionary Note Regarding Forward-Looking Statements? and ?Item 1A. Risk Factors,? and in the
company?s most recently filed Quarterly Report on Form 10-Q 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 of Johnson & Johnson nor Johnson & Johnson undertakes to update any
forward-looking statement as a result of new information or future events or developments.
Kyprolis? is a registered trademark of Amgen Inc.