Biweekly dosing with TECVAYLI®, the first approved
BCMA-targeting bispecific antibody, provides patients with dosing
flexibility
HORSHAM,
Pa., Feb. 20, 2024 /PRNewswire/ -- Johnson
& Johnson announced today that the U.S. Food and Drug
Administration (FDA) has approved the supplemental Biologics
License Application (sBLA) for
TECVAYLI® (teclistamab-cqyv) for a reduced dosing
frequency of 1.5 mg/kg every two weeks (Q2W) in patients with
relapsed or refractory multiple myeloma (RRMM) who have achieved
and maintained a complete response (CR) or better for a minimum of
six months.1 There is a continued unmet need for
patients with multiple myeloma and this approval allows increased
flexibility in dosing schedule for appropriate patients with a
weight-based regimen.
TECVAYLI®, which is administered subcutaneously, was
the first bispecific antibody targeting B-cell maturation antigen
(BCMA) on multiple myeloma cells and CD3 on T-cells to activate an
immune response.2 TECVAYLI® was
approved in October 2022 for the
treatment of adult patients with RRMM who received at least four
prior lines of therapy, including a proteasome inhibitor, an
immunomodulatory drug, and an anti-CD38 monoclonal
antibody.2 This indication is approved under accelerated
approval based on response rate. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. TECVAYLI® has
been prescribed to more than 3,600 patients in the U.S. since
approval.3
This approval is based on results from the Phase 1/2 MajesTEC-1
study (Phase 1: NCT03145181; Phase 2: NCT04557098). In the
Phase 1/2 MajesTEC-1 study, patients were initially treated with
the recommended Phase 2 dose (RP2D) of 1.5 mg/kg
TECVAYLI® weekly (QW) administered
subcutaneously.4 Patients who achieved a confirmed
CR or better for six months or longer (Phase 2), were eligible to
reduce dosing frequency to 1.5 mg/kg Q2W until disease progression
or unacceptable toxicity.1,4
"TECVAYLI is the only BCMA-targeted immune-based therapy with
weight-based dosing. Today's approval of biweekly dosing for
eligible patients will further enable clinicians to meet the
individual needs of patients who may want flexibility in their
dosing schedules," said Rachel Kobos, M.D., Vice President,
Oncology Research & Development, Johnson & Johnson
Innovative Medicine. "As the first bispecific approved for the
treatment of multiple myeloma, combined with the longest in-market
experience by physicians, TECVAYLI is another example of our
commitment to pioneering cutting-edge research to help improve
outcomes for patients with multiple myeloma."
About the MajesTEC-1 Study
MajesTEC-1 (NCT03145181, NCT04557098), is a Phase 1/2
single-arm, open-label, multicohort, multicenter dose-escalation
study to evaluate the safety and efficacy of teclistamab in adults
with RRMM who received three or more prior lines of therapy
(n=165).5,6
Phase 1 of the study (NCT03145181) was conducted in two parts:
dose escalation (Part 1) and dose expansion (Part
2).6 It evaluated safety, tolerability,
pharmacokinetics, and preliminary efficacy of teclistamab in adult
participants with RRMM.6 Phase 2 of the study
(NCT04557098) evaluated the efficacy of teclistamab at the RP2D,
established at subcutaneous 1.5 mg/kg weekly, as measured by
ORR.5
TECVAYLI® IMPORTANT SAFETY
INFORMATION
WARNING: CYTOKINE
RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR
CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release
syndrome (CRS), including life-threatening or fatal reactions, can
occur in patients receiving TECVAYLI®. Initiate
treatment with TECVAYLI® step-up dosing schedule to
reduce risk of CRS. Withhold TECVAYLI® until CRS
resolves or permanently discontinue based on
severity.
Neurologic toxicity,
including Immune Effector Cell-Associated Neurotoxicity Syndrome
(ICANS) and serious and life-threatening reactions, can occur in
patients receiving TECVAYLI®. Monitor patients for signs
or symptoms of neurologic toxicity, including ICANS, during
treatment. Withhold TECVAYLI® until neurologic toxicity
resolves or permanently discontinue based on
severity.
TECVAYLI®
is available only through a restricted program called the
TECVAYLI® and TALVEY™ Risk Evaluation and Mitigation
Strategy (REMS).
|
INDICATION AND USAGE
TECVAYLI® (teclistamab-cqyv) is a bispecific B-cell
maturation antigen (BCMA)-directed CD3 T-cell engager indicated for
the treatment of adult patients with relapsed or refractory
multiple myeloma who have received at least four prior lines of
therapy, including a proteasome inhibitor, an immunomodulatory
agent and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on
response rate. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trial(s).
WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome -
TECVAYLI® can cause cytokine release syndrome (CRS),
including life-threatening or fatal reactions. In the clinical
trial, CRS occurred in 72% of patients who received
TECVAYLI® at the recommended dose, with Grade 1 CRS
occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%.
Recurrent CRS occurred in 33% of patients. Most patients
experienced CRS following step-up dose 1 (42%), step-up dose 2
(35%), or the initial treatment dose (24%). Less than 3% of
patients developed first occurrence of CRS following subsequent
doses of TECVAYLI®. The median time to onset of CRS was
2 (range: 1 to 6) days after the most recent dose with a median
duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of
CRS included, but were not limited to, fever, hypoxia, chills,
hypotension, sinus tachycardia, headache, and elevated liver
enzymes (aspartate aminotransferase and alanine aminotransferase
elevation).
Initiate therapy according to TECVAYLI® step-up
dosing schedule to reduce risk of CRS. Administer pretreatment
medications to reduce risk of CRS and monitor patients following
administration of TECVAYLI® accordingly. At the first
sign of CRS, immediately evaluate patient for hospitalization.
Administer supportive care based on severity and consider further
management per current practice guidelines. Withhold or permanently
discontinue TECVAYLI® based on severity.
TECVAYLI® is available only through a restricted
program under a REMS.
Neurologic Toxicity including ICANS -
TECVAYLI® can cause serious or life-threatening
neurologic toxicity, including Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS).
In the clinical trial, neurologic toxicity occurred in 57% of
patients who received TECVAYLI® at the recommended dose,
with Grade 3 or 4 neurologic toxicity occurring in 2.4% of
patients. The most frequent neurologic toxicities were headache
(25%), motor dysfunction (16%), sensory neuropathy (15%), and
encephalopathy (13%). With longer follow-up, Grade 4 seizure and
fatal Guillain-Barré syndrome (one patient each) occurred in
patients who received TECVAYLI®.
In the clinical trial, ICANS was reported in 6% of patients who
received TECVAYLI® at the recommended dose. Recurrent
ICANS occurred in 1.8% of patients. Most patients experienced ICANS
following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the
initial treatment dose (1.8%). Less than 3% of patients developed
first occurrence of ICANS following subsequent doses of
TECVAYLI®. The median time to onset of ICANS was 4
(range: 2 to 8) days after the most recent dose with a median
duration of 3 (range: 1 to 20) days. The most frequent clinical
manifestations of ICANS reported were confusional state and
dysgraphia. The onset of ICANS can be concurrent with CRS,
following resolution of CRS, or in the absence of CRS.
Monitor patients for signs and symptoms of neurologic toxicity
during treatment. At the first sign of neurologic toxicity,
including ICANS, immediately evaluate patient and provide
supportive therapy based on severity. Withhold or permanently
discontinue TECVAYLI® based on severity per
recommendations and consider further management per current
practice guidelines.
Due to the potential for neurologic toxicity, patients are at
risk of depressed level of consciousness. Advise patients to
refrain from driving or operating heavy or potentially dangerous
machinery during and for 48 hours after completion of
TECVAYLI® step-up dosing schedule and in the event of
new onset of any neurologic toxicity symptoms until neurologic
toxicity resolves.
TECVAYLI® is available only through a restricted
program under a REMS.
TECVAYLI® and TALVEY™ REMS -
TECVAYLI® is available only through a restricted program
under a REMS called the TECVAYLI® and TALVEY™ REMS
because of the risks of CRS and neurologic toxicity, including
ICANS.
Hepatotoxicity - TECVAYLI® can cause
hepatotoxicity, including fatalities. In patients who received
TECVAYLI® at the recommended dose in the clinical trial,
there was one fatal case of hepatic failure. Elevated aspartate
aminotransferase (AST) occurred in 34% of patients, with Grade 3 or
4 elevations in 1.2%. Elevated alanine aminotransferase (ALT)
occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%.
Elevated total bilirubin occurred in 6% of patients with Grade 3 or
4 elevations in 0.6%. Liver enzyme elevation can occur with or
without concurrent CRS.
Monitor liver enzymes and bilirubin at baseline and during
treatment as clinically indicated. Withhold TECVAYLI® or
consider permanent discontinuation of TECVAYLI® based on
severity.
Infections - TECVAYLI® can cause severe,
life-threatening, or fatal infections. In patients who received
TECVAYLI® at the recommended dose in the clinical trial,
serious infections, including opportunistic infections, occurred in
30% of patients, with Grade 3 or 4 infections in 35%, and fatal
infections in 4.2%. Monitor patients for signs and symptoms of
infection prior to and during treatment with TECVAYLI®
and treat appropriately. Administer prophylactic antimicrobials
according to guidelines. Withhold TECVAYLI® or consider
permanent discontinuation of TECVAYLI® based on
severity.
Monitor immunoglobulin levels during treatment with
TECVAYLI® and treat according to guidelines, including
infection precautions and antibiotic or antiviral prophylaxis.
Neutropenia - TECVAYLI® can cause
neutropenia and febrile neutropenia. In patients who received
TECVAYLI® at the recommended dose in the clinical trial,
decreased neutrophils occurred in 84% of patients, with Grade 3 or
4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3%
of patients.
Monitor complete blood cell counts at baseline and periodically
during treatment and provide supportive care per local
institutional guidelines. Monitor patients with neutropenia for
signs of infection. Withhold TECVAYLI® based on
severity.
Hypersensitivity and Other Administration Reactions -
TECVAYLI® can cause both systemic administration-related
and local injection-site reactions. Systemic Reactions - In
patients who received TECVAYLI® at the recommended dose
in the clinical trial, 1.2% of patients experienced
systemic-administration reactions, which included Grade 1 recurrent
pyrexia and Grade 1 swollen tongue. Local Reactions - In patients
who received TECVAYLI® at the recommended dose in the
clinical trial, injection-site reactions occurred in 35% of
patients, with Grade 1 injection-site reactions in 30% and Grade 2
in 4.8%. Withhold TECVAYLI® or consider permanent
discontinuation of TECVAYLI® based on severity.
Embryo-Fetal Toxicity - Based on its mechanism of
action, TECVAYLI® may cause fetal harm when administered
to a pregnant woman. Advise pregnant women of the potential risk to
the fetus. Advise females of reproductive potential to use
effective contraception during treatment with TECVAYLI®
and for 5 months after the last dose.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) were pyrexia, CRS,
musculoskeletal pain, injection site reaction, fatigue, upper
respiratory tract infection, nausea, headache, pneumonia, and
diarrhea. The most common Grade 3 to 4 laboratory abnormalities
(≥20%) were decreased lymphocytes, decreased neutrophils, decreased
white blood cells, decreased hemoglobin, and decreased
platelets.
Please read full Prescribing Information, including Boxed
WARNING, for TECVAYLI®.
About TECVAYLI®
TECVAYLI® (teclistamab-cqyv) received approval from
the U.S. FDA in October 2022 as an
off-the-shelf (or ready-to-use) antibody that is administered
as a subcutaneous treatment for adult patients with relapsed or
refractory multiple myeloma (RRMM) who have received at least four
prior lines of therapy, including a proteasome inhibitor, an
immunomodulatory agent and an anti-CD38 antibody.2 The
European Commission (EC) granted TECVAYLI® conditional
marketing authorization (CMA) in August
2022 as monotherapy for the treatment of adult patients with
RRMM who have received at least three prior therapies, including a
proteasome inhibitor, an immunomodulatory agent and an anti-CD38
antibody, and have demonstrated disease progression since the last
therapy. In August 2023, the EC
granted the approval of a Type II variation application for
TECVAYLI®, providing the option for a reduced dosing
frequency of 1.5 mg/kg every two weeks in patients who have
achieved a complete response (CR) or better for a minimum of six
months. TECVAYLI® is a first-in-class, bispecific
T-cell engager antibody therapy that uses innovative science to
activate the immune system by binding to the CD3 receptor expressed
on the surface of T-cells and to the B-cell maturation antigen
(BCMA) expressed on the surface of multiple myeloma cells and some
healthy B-lineage cells.
For more information, visit www.TECVAYLI.com.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a
type of white blood cell called plasma cells, which are found in
the bone marrow.7 In multiple myeloma, these plasma
cells proliferate and spread rapidly and replace normal cells in
the bone marrow with tumors.8 Multiple myeloma is
the third most common blood cancer worldwide and remains an
incurable disease.9 In 2024, it was estimated that
more than 35,000 people will be diagnosed with multiple myeloma in
the U.S. and more than 12,000 people would die from the
disease.10 People living with multiple myeloma have
a 5-year survival rate of 59.8 percent.11 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 and kidney problems or
infections.12,13
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 TECVAYLI®
(teclistamab-cqyv). 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.
© Johnson & Johnson, Inc. 2024. All rights reserved.
1TECVAYLI® U.S. Prescribing
Information.
2U.S. FDA Approves TECVAYLI®
(teclistamab-cqyv), the First Bispecific T-cell Engager Antibody
for the Treatment of Patients with Relapsed or Refractory Multiple
Myeloma.
https://www.jnj.com/u-s-fda-approves-tecvayli-teclistamab-cqyv-the-first-bispecific-t-cell-engager-antibody-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma.
October 2022.
3Data on File. Janssen Biotech, Inc. IQVIA DDD
10/25/2022 - 01/26/2024
4Usmani S et al. Durability of Responses With
Biweekly Dosing of Teclistamab in Patients With Relapsed/Refractory
Multiple Myeloma Achieving a Clinical Response in the MajesTEC-1
Study. 2023 ASCO Annual Meeting – American Society of Clinical
Oncology. June 2023.
https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8034#C1916414
5A Study of Teclistamab in Participants With Relapsed
or Refractory Multiple Myeloma (MajesTEC-1).
https://clinicaltrials.gov/ct2/show/NCT04557098. Accessed
February 2024.
6Dose Escalation Study of Teclistamab, a
Humanized BCMA*CD3 Bispecific Antibody, in Participants With
Relapsed or Refractory Multiple Myeloma
(MajesTEC-1). https://clinicaltrials.gov/ct2/show/NCT03145181.
Accessed February 2024.
7Rajkumar 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
8National Cancer Institute. Plasma Cell Neoplasms.
https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq.
Accessed February 2024.
9City of Hope. Multiple Myeloma: Causes, Symptoms
& Treatments.
https://www.cancercenter.com/cancer-types/multiple-myeloma.
Accessed February 2024.
10American Cancer Society. Key Statistics About
Multiple Myeloma.
https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370%20in%20women. Accessed
February 2024.
11SEER Explorer: An interactive website for SEER
cancer statistics [Internet]. Surveillance Research Program,
National Cancer Institute. https://seer.cancer.gov/explorer/.
Accessed February 2024.
12American Cancer Society. What is Multiple Myeloma?
https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html.
Accessed February 2024.
13American Cancer Society. Multiple Myeloma Early
Detection, Diagnosis, and Staging
https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html.
Accessed February 2024.
Media contact:
Christie Corbett
1-857-636-0211
Satu Glawe
+49
172-294-6264
|
Investor contact: Raychel Kruper
investor-relations@its.jnj.com
U.S. medical inquiries: +1 800
526-7736
|
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