Janssen Submits Application Seeking U.S. FDA Approval of DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) for the Treatment of Patients with Light Chain (AL) Amyloidosis

Application is based on positive results from the Phase 3 ANDROMEDA study evaluating the efficacy
and safety of combination therapy with DARZALEX FASPRO™
RARITAN, NJ, September 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 FASPRO™
(daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, for the
treatment of patients with light chain (AL) amyloidosis, a rare and potentially fatal disease for
which there are no currently approved therapies.
1,2 The sBLA is supported by positive results from
the Phase 3 ANDROMEDA study, which were presented as a late-breaking abstract at the 25th
European Hematology Association Annual Congress in June. ANDROMEDA evaluated subcutaneous
daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd)
compared to VCd alone and met its primary endpoint of overall hematologic complete response
“We are excited about the potential of helping patients with AL amyloidosis who currently have no
FDA-approved therapies for the treatment of their disease,” said Craig Tendler, M.D., Vice
President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research &
Development, LLC. “The results from the Phase 3 ANDROMEDA study also provide preliminary
evidence of DARZALEX FASPRO’s potential to modify the organ damage that is a hallmark of this
serious disease with high unmet needs and we look forward to collaborating with the agency in the
review of the application.”
The sBLA is being reviewed under the FDA Real-Time Oncology Review (RTOR) program, which
allows data for certain applications to be reviewed before the applicant formally submits the
complete application. The RTOR program aims to explore a more efficient review process to help
ensure treatments are available as soon as possible for patients. Selection into the RTOR program
does not guarantee or influence approvability of the supplemental application.
The submission is also being reviewed under Project Orbis, an initiative of the FDA Oncology Center
of Excellence, which provides a framework for concurrent submission and review of oncology
medicine applications among international regulatory agencies.
AL amyloidosis is a life-threatening disorder that occurs when plasma cells in the bone marrow
produce abnormal light chains, that form amyloid deposits, which build up in vital organs and
eventually cause organ deterioration.1,2 The disease can affect different organs in different people,
but the most frequently affected organs are the heart, kidneys, liver, spleen, GI tract and nervous
4 Diagnosis of AL amyloidosis is often delayed because patients present with non-specific
symptoms that mimic other conditions, resulting in a poor prognosis.
5 There are currently no FDAapproved therapies to treat this devastating disease. While AL amyloidosis is the most common
type of amyloidosis, it remains a rare disease with an estimated 30,000 to 45,000 people living
with the disease in the U.S. and Europe.6 Each year, an estimated 4,500 people develop AL
amyloidosis in the U.S. alone.
About the ANDROMEDA Study
ANDROMEDA (NCT03201965) is an ongoing Phase 3, randomized, open-label study investigating
the safety and efficacy of daratumumab and hyaluronidase-fihj in combination with bortezomib,
cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone, for the treatment of
patients with newly diagnosed light chain (AL) amyloidosis. The study includes 388 patients with
newly diagnosed AL amyloidosis with measurable hematologic disease and one or more organs
affected. The primary endpoint is overall complete hematologic response rate by intent-to-treat
(ITT). Secondary endpoints include major organ deterioration progression-free survival, event-free
survival, organ response rate, overall survival, and time to hematologic response, among others.
Janssen is committed to exploring the potential of DARZALEX FASPRO™ (daratumumab and
hyaluronidase-fihj) for patients with multiple myeloma (MM) across the spectrum of the disease.
In August 2012, Janssen entered into an exclusive global license and development agreement with
Genmab A/S to develop, manufacture and commercialize DARZALEX®.
FASPRO™ (daratumumab and hyaluronidase human-fihj) was approved as the only subcutaneous
CD38-directed antibody approved to treat patients with MM.
9 DARZALEX FASPRO™ is coformulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug
delivery technology.
CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of
the stage of disease.4 Daratumumab binds to CD38 and inhibits tumor cell growth causing myeloma
cell death.5 DARZALEX FASPRO™ may also have an effect on normal cells.10 Data across seven
Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumabbased regimens resulted in significant improvement in progression-free survival and/or overall
survival.11,12,13,14,15,16,17,18 Additional studies are underway to assess the efficacy and safety of
DARZALEX FASPRO™ in the treatment of other malignant and pre-malignant hematologic diseases
in which CD38 is expressed, including smoldering myeloma and in AL amyloidosis.19,20
Please see full Prescribing Information at www.DARZALEX.com.
DARZALEX FASPRO™ is contraindicated in patients with a history of severe hypersensitivity to
daratumumab, hyaluronidase or any of the components of the formulation.
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™.
Systemic Reactions
In a pooled safety population of 490 patients who received DARZALEX FASPRO™ as monotherapy or
in combination, 11% of patients experienced a systemic administration-related reaction (Grade 2:
3.9%, Grade 3: 1.4%). Systemic administration-related reactions occurred in 10% of patients with
the first injection, 0.2% with the second injection, and cumulatively 0.8% with subsequent injections.
The median time to onset was 3.7 hours (range: 9 minutes to 3.5 days). Of the 84 systemic
administration-related reactions that occurred in 52 patients, 73 (87%) occurred on the day of
DARZALEX FASPRO™ administration. Delayed systemic administration-related reactions have
occurred in less than 1% of the patients.
Severe reactions included hypoxia, dyspnea, hypertension and tachycardia. 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, pruritis, chills, vomiting, nausea, and hypotension.
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.
Local Reactions
In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2
reactions in 0.6%. The most frequent (>1%) injection-site reaction was injection site erythema.
These local reactions occurred a median of 7 minutes (range: 0 minutes to 4.7 days) after starting
administration of DARZALEX FASPRO™. Monitor for local reactions and consider symptomatic
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.
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 is contraindicated in pregnant women,
because lenalidomide may cause birth defects and death of the unborn child. Refer to the
lenalidomide 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
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 DARZALEX FASPRO™-treated patients with IgG kappa myeloma protein.
Adverse Reactions
The most common adverse reaction (≥20%) with DARZALEX FASPRO™ monotherapy is upper
respiratory tract infection.
The most common adverse reactions (≥20%) with D-VMP are upper respiratory tract infection,
constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia,
vomiting, and back pain. The most common adverse reactions (≥20%) with D-Rd are fatigue,
diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia and
The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO™ are
decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and
decreased hemoglobin.
Please see full Prescribing Information at www.DARZALEX.com.
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 and
www.twitter.com/JanssenUS. 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 FASPRO™. 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 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 29, 2019,
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. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to
update any forward-looking statement as a result of new information or future events or
ENHANZE® is a registered trademark of Halozyme.
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Shiwani Sharma

Shiwani Sharma is a Senior Editor at PharmaShots. She has in-depth knowledge of lifesciences industry including pharma and biotech sectors. She also covers news in field of Digital Health, Medtech and regulatory approvals from the US FDA, EU, and other global regulatory bodies in the industry. Additionally, she also writes Whitepapers, analysis reports, blogs on pharma and biotech industry. She is graduate in Biotechnology. She can be contacted on shiwani@pharmashots.com

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