Findings from first-ever quadruplet therapy study with
subcutaneous DARZALEX FASPRO® showed 60
percent reduction in risk of disease progression or death
New regimen solidifies DARZALEX
FASPRO® as a foundational
frontline therapy in multiple myeloma with potential to
significantly delay disease progression
HORSHAM,
Pa., July 30, 2024 /PRNewswire/ -- Johnson
& Johnson (NYSE:JNJ) announced today that the U.S. Food and
Drug Administration (FDA) approved DARZALEX
FASPRO® (daratumumab and hyaluronidase-fihj) in
combination with bortezomib, lenalidomide and dexamethasone (D-VRd)
for induction and consolidation in patients with newly diagnosed
multiple myeloma (NDMM) who are eligible for an autologous stem
cell transplant (ASCT).1 Patients will have the
opportunity to receive this DARZALEX
FASPRO®-based quadruplet therapy at initial
diagnosis, providing them with a new treatment that may
significantly improve outcomes.
This approval is supported by data from the Phase 3 PERSEUS
study evaluating DARZALEX FASPRO® in a regimen
that included D-VRd induction and consolidation therapy compared to
bortezomib, lenalidomide and dexamethasone (VRd) during induction
and consolidation in patients with NDMM eligible for
ASCT.1 Following consolidation, patients received an
investigational treatment regimen for maintenance that included
DARZALEX FASPRO® in combination with
lenalidomide or lenalidomide alone.1
"Multiple myeloma has a highly varied clinical course among
patients and in each individual patient, and there is a continued
need for innovation and therapies that employ different targets and
combinations to provide patients with treatment options at
diagnosis and throughout the course of their disease," said Amrita
Y. Krishnan, M.D., Professor and Director of the Judy and Bernard
Briskin Multiple Myeloma Center, City of Hope.* "The efficacy data
supporting this new quadruplet regimen, combined with its
established safety and tolerability profile, provide compelling
evidence that adding D-VRd upon initial diagnosis as compared to
VRd can deepen responses and prolong remissions in the context of
autologous stem cell transplantation."
Findings from the PERSEUS study demonstrated a significant
improvement in the primary endpoint of progression-free survival
(PFS), with D-VRd reducing the risk of disease progression or death
by 60 percent compared to VRd (HR [95% CI]: 0.40 [0.29, 0.57];
p-value < 0.0001).1 Treatment with D-VRd
induction and consolidation resulted in deeper responses at the end
of consolidation compared to VRd: minimal residual disease (MRD)
negativity rates of 57.5 percent vs. 32.5 percent, and
MRD-negativity rates in patients with complete response (CR) or
better of 76.6 percent vs. 58.5 percent,
respectively.1
"This latest indication for DARZALEX FASPRO-based
quadruplet therapy demonstrated a clinically significant reduction
in disease progression or death during first-line treatment when
patients are likely to experience their deepest responses," said
Jordan Schecter, M.D., Vice
President, Disease Area Leader, Multiple Myeloma, Johnson &
Johnson. "Today's approval embodies our commitment to setting new
standards of care for patients newly diagnosed with multiple
myeloma who are transplant eligible."
The overall safety profile of D-VRd was consistent with the
known safety profiles for DARZALEX FASPRO® and
VRd.1 The most common adverse reactions (≥20%) in
patients with multiple myeloma who received D-VRd are peripheral
neuropathy, fatigue, edema, pyrexia, upper respiratory infection,
constipation, diarrhea, musculoskeletal pain, insomnia, and
rash.1
About the PERSEUS Study
The PERSEUS study is being
conducted in collaboration with the European Myeloma Network as the
sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3
study comparing the efficacy and safety of D-VRd during induction
and consolidation versus VRd during induction and consolidation in
patients with NDMM eligible for ASCT. Following consolidation,
patients received an investigational treatment regimen for
maintenance that included DARZALEX
FASPRO® in combination with
lenalidomide or lenalidomide alone. The trial was not designed to
isolate the effect of DARZALEX
FASPRO® in the maintenance phase of
treatment. The efficacy of DARZALEX
FASPRO® in combination with
lenalidomide for maintenance has not been established. The primary
endpoint is PFS, and secondary endpoints include overall CR or
better rate, and overall MRD-negativity (in patients with CR or
better). The median age is 61.0 (range, 32-70) years for patients
in the D-VRd arm and 59.0 (range, 31-70) years for patients in the
VRd arm.2 The study is being conducted in 14
countries in Europe and
Australia.
About Multiple Myeloma
Multiple myeloma is a
blood cancer that affects a type of white blood cell called plasma
cells, which are found in the bone marrow.3 In
multiple myeloma, these malignant plasma cells proliferate and
replace normal cells in the bone marrow.4 Multiple
myeloma is the second most common blood cancer worldwide and
remains an incurable disease.5 In 2024, it is estimated
that more than 35,000 people will be diagnosed with
multiple myeloma in the U.S. and more than 12,000 will die
from the disease.6 People with multiple myeloma
have a 5-year survival rate of 59.8 percent.6 While
some people diagnosed with multiple myeloma initially have no
symptoms, most patients are diagnosed due to symptoms that can
include bone fracture or pain, low red blood cell counts,
tiredness, high calcium levels, kidney problems or
infections.7,8
About DARZALEX FASPRO®
DARZALEX
FASPRO® (daratumumab and hyaluronidase-fihj)
received U.S. FDA approval in May 2020 and is approved for
nine indications in multiple myeloma, four of which are for
frontline treatment in newly diagnosed patients who are transplant
eligible or ineligible.1 It is the only subcutaneous
CD38-directed antibody approved to treat patients with multiple
myeloma. DARZALEX FASPRO® is co-formulated with
recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's
ENHANZE® drug delivery technology.
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 daratumumab.
For more information, visit https://www.darzalexhcp.com.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT
SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and
hyaluronidase-fihj) is indicated for the treatment of adult
patients with multiple myeloma:
- In combination with bortezomib, lenalidomide, and dexamethasone
for induction and consolidation in newly diagnosed patients who are
eligible for autologous stem cell transplant
- In combination with bortezomib, melphalan, and prednisone in
newly diagnosed patients who are ineligible for autologous stem
cell transplant
- In combination with lenalidomide and dexamethasone in newly
diagnosed patients who are ineligible for autologous stem cell
transplant and in patients with relapsed or refractory multiple
myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone
in newly diagnosed patients who are eligible for autologous stem
cell transplant
- In combination with pomalidomide and dexamethasone in patients
who have received at least one prior line of therapy including
lenalidomide and a proteasome inhibitor (PI)
- In combination with carfilzomib and dexamethasone in patients
with relapsed or refractory multiple myeloma who have received one
to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients
who have received at least one prior therapy
- As monotherapy in patients who have received at least three
prior lines of therapy including a PI and an immunomodulatory agent
or who are double refractory to a PI and an immunomodulatory
agent
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX FASPRO® is contraindicated in patients
with a history of severe hypersensitivity to daratumumab,
hyaluronidase, or any of the components of the
formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or
life-threatening reactions, and local injection-site reactions can
occur with DARZALEX FASPRO®. Fatal reactions have
been reported with daratumumab-containing products, including
DARZALEX FASPRO®.
Systemic Reactions
In a pooled safety population of 1249 patients with multiple
myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who
received DARZALEX FASPRO® as monotherapy or in
combination, 7% of patients experienced a systemic
administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%,
Grade 4: 0.1%). Systemic administration-related reactions occurred
in 7% of patients with the first injection, 0.2% with the second
injection, and cumulatively 1% with subsequent injections. The
median time to onset was 2.9 hours (range: 5 minutes to
3.5 days). Of the 165 systemic administration-related
reactions that occurred in 93 patients, 144 (87%)
occurred on the day of DARZALEX FASPRO®
administration. Delayed systemic administration-related reactions
have occurred in 1% of the patients.
Severe reactions included hypoxia, dyspnea, hypertension,
tachycardia, and ocular adverse reactions, including choroidal
effusion, acute myopia, and acute angle closure glaucoma. Other
signs and symptoms of systemic administration-related reactions may
include respiratory symptoms, such as bronchospasm, nasal
congestion, cough, throat irritation, allergic rhinitis, and
wheezing, as well as anaphylactic reaction, pyrexia, chest pain,
pruritus, chills, vomiting, nausea, hypotension, and blurred
vision.
Pre-medicate patients with histamine-1 receptor antagonist,
acetaminophen, and corticosteroids. Monitor patients for systemic
administration-related reactions, especially following the first
and second injections. For anaphylactic reaction or
life-threatening (Grade 4) administration-related reactions,
immediately and permanently discontinue DARZALEX
FASPRO®. Consider administering corticosteroids
and other medications after the administration of DARZALEX
FASPRO® depending on dosing regimen and medical
history to minimize the risk of delayed (defined as occurring the
day after administration) systemic administration-related
reactions.
Ocular adverse reactions, including acute myopia and narrowing
of the anterior chamber angle due to ciliochoroidal effusions with
potential for increased intraocular pressure or glaucoma, have
occurred with daratumumab-containing products. If ocular symptoms
occur, interrupt DARZALEX FASPRO® and seek
immediate ophthalmologic evaluation prior to restarting DARZALEX
FASPRO®.
Local Reactions
In this pooled safety population, injection-site reactions occurred
in 7% of patients, including Grade 2 reactions in 0.8%. The
most frequent (>1%) injection-site reaction was injection-site
erythema. These local reactions occurred a median of 5 minutes
(range: 0 minutes to 6.5 days) after starting
administration of DARZALEX FASPRO®. Monitor for
local reactions and consider symptomatic
management.
Neutropenia
Daratumumab 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. Consider withholding DARZALEX FASPRO®
until recovery of neutrophils. In lower body weight patients
receiving DARZALEX FASPRO®, higher rates of Grade
3-4 neutropenia were observed.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background
therapy. Monitor complete blood cell counts periodically during
treatment according to manufacturer's prescribing information for
background therapies. Consider withholding DARZALEX
FASPRO® until recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX
FASPRO® can cause fetal harm when administered to
a pregnant woman. DARZALEX FASPRO® may cause
depletion of fetal immune cells and decreased bone density. Advise
pregnant women of the potential risk to a fetus. Advise females
with reproductive potential to use effective contraception during
treatment with DARZALEX FASPRO® and for 3 months
after the last dose.
The combination of DARZALEX FASPRO® with
lenalidomide, thalidomide, or pomalidomide is contraindicated in
pregnant women because lenalidomide, thalidomide, and pomalidomide
may cause birth defects and death of the unborn child. Refer to the
lenalidomide, thalidomide, or pomalidomide prescribing information
on use during pregnancy.
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
administration. 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 FASPRO®. Type and screen
patients prior to starting DARZALEX
FASPRO®.
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (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 DARZALEX FASPRO®-treated
patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥20%) with
DARZALEX FASPRO® monotherapy is upper respiratory
tract infection. The most common adverse reactions with
combination therapy (≥20% for any combination) include fatigue,
nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough,
muscle spasms, back pain, vomiting, hypertension, upper respiratory
tract infection, peripheral neuropathy, peripheral sensory
neuropathy, constipation, pneumonia, edema, peripheral edema,
musculoskeletal pain, and rash.
The most common hematology laboratory abnormalities (≥40%) with
DARZALEX FASPRO® are decreased leukocytes,
decreased lymphocytes, decreased neutrophils, decreased platelets,
and decreased hemoglobin.
Please click here to read full Prescribing
Information for DARZALEX FASPRO®.
About Johnson & Johnson
At Johnson &
Johnson, we believe health is everything. Our strength in
healthcare innovation empowers us to build a world where complex
diseases are prevented, treated, and cured, where treatments are
smarter and less invasive, and solutions are personal. Through our
expertise in Innovative Medicine and MedTech, we are uniquely
positioned to innovate across the full spectrum of healthcare
solutions today to deliver the breakthroughs of tomorrow, and
profoundly impact health for humanity. Learn more at
https://www.jnj.com/ or at
www.janssen.com/johnson-johnson-innovative-medicine. Follow us
at @JanssenUS and @JNJInnovMed. Janssen Research &
Development, LLC and Janssen Biotech, Inc. are both Johnson &
Johnson companies.
Cautions Concerning Forward-Looking
Statements
This press release contains
"forward-looking statements" as defined in the Private Securities
Litigation Reform Act of 1995 regarding product development and the
potential benefits and treatment impact of DARZALEX
FASPRO® (daratumumab and hyaluronidase-fihj).
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 Janssen
Research & Development, LLC, Janssen Biotech, Inc. 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 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
31, 2023, including in the sections captioned "Cautionary
Note Regarding Forward-Looking Statements" and "Item 1A. Risk
Factors," and in Johnson & Johnson's subsequent Quarterly
Reports on Form 10-Q and other 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. None of Janssen Research & Development, LLC, Janssen
Biotech, Inc., nor Johnson & Johnson undertake to update any
forward-looking statement as a result of new information or future
events or developments.
*Dr. Amrita Y. Krishnan has provided consulting, advisory, and
speaking services to Johnson & Johnson; she has not been paid
for any media work.
________________________________
|
1 DARZALEX
FASPRO® U.S. Prescribing Information.
|
2 Pieter
Sonneveld, Dimopoulos MA, Boccadoro M, et al. Daratumumab,
Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.
The New England Journal of Medicine. Accessed July 2024.
https://www.nejm.org/doi/full/10.1056/NEJMoa2312054
|
3 Rajkumar
SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification
and Management. Am J Hematol.
2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
|
4 National
Cancer Institute. Plasma Cell Neoplasms. Accessed July 2024.
Available at:
https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
|
5 Multiple
Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms
& Treatments. Accessed July 2024. Available at:
https://www.cancercenter.com/cancer-types/multiple-myeloma
|
6 American
Cancer Society. Myeloma Cancer Statistics. Accessed July 2024.
Available
at: https://cancerstatisticscenter.cancer.org/types/myeloma
|
7 American
Cancer Society. What is Multiple Myeloma? Accessed July 2024.
Available
at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html
|
8 American
Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and
Staging. Accessed July 2024. Available at:
https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html
|
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