- Approval is based on positive data from the Phase 3 ECHELON-3
trial, which demonstrated ADCETRIS regimen reduced the risk of
death by 37%, a statistically significant, clinically meaningful
improvement in overall survival (OS), compared to lenalidomide and
rituximab plus placebo
- ECHELON-3 is the first Phase 3 trial to demonstrate OS
advantage over lenalidomide and rituximab plus placebo for patients
with at least 2 prior lines of therapy with R/R diffuse large
B-cell lymphoma (DLBCL)
- Milestone represents the eighth FDA-approved indication for
ADCETRIS, reinforcing its use as a standard of care for certain
lymphomas
Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and
Drug Administration (FDA) has approved the supplemental Biologics
License Application (sBLA) for ADCETRIS® (brentuximab vedotin) in
combination with lenalidomide and a rituximab product for the
treatment of adult patients with relapsed or refractory large
B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma
(DLBCL) not otherwise specified (NOS), DLBCL arising from indolent
lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more
lines of systemic therapy who are not eligible for autologous
hematopoietic stem cell transplantation (auto-HSCT) or chimeric
antigen receptor (CAR) T-cell therapy.
“Each year, more than 3,500 patients in the U.S. with this
aggressive form of non-Hodgkin lymphoma experience treatment
failure or relapse after two prior lines of therapy,” said Roger
Dansey, M.D., Chief Oncology Officer, Pfizer. “Today’s approval
further reinforces the important role of ADCETRIS as an existing
standard of care with overall survival improvement shown for
certain types of lymphomas, and now allows physicians to have an
option beyond chemotherapy or CAR-Ts for patients with
relapsed/refractory large B-cell lymphoma.”
The approval is based on efficacy and safety data from the Phase
3 ECHELON-3 study, which demonstrated a statistically significant
and clinically meaningful improvement in overall survival (OS) in
patients with relapsed/refractory DLBCL who received ADCETRIS in
combination with lenalidomide and rituximab. The study included
patients who were heavily pre-treated, some of whom had received
prior CAR-T therapy, and survival benefit was observed irrespective
of CD30 expression.
“Patients with large B-cell lymphoma can face a challenging
journey, with too many patients enduring multiple rounds of
chemotherapy and even CAR-T therapy with limited success,” said
principal investigator Dr. Craig Portell, Associate Professor,
University of Virginia. “For patients who have previously faced
setbacks with other therapies, ADCETRIS provides a new therapeutic
option with outpatient administration and proven safety and
efficacy.”
LBCL is a type of non-Hodgkin lymphoma (NHL), that affects
immune cells called B lymphocytes, a type of white blood cell
crucial to the body's immune system. DLBCL is the most common,
aggressive and difficult-to-treat form of the disease. More than
25,000 cases of DLBCL are diagnosed each year in the United States,
accounting for more than 25% of all lymphoma cases. Up to 40% of
patients relapse or have refractory disease after frontline
treatment, and more than 3,500 patients a year fail two prior lines
of therapy and require third-line therapy. Despite recent treatment
advances including bispecifics and CAR-T therapy, there remains a
high unmet need for patients who are not eligible for these
treatments or whose disease returns following treatment with these
therapies.
The ECHELON-3 study showed that the ADCETRIS combination reduced
patients’ risk of death by 37% compared to placebo in combination
with lenalidomide and rituximab (HR 0.63 [95% CI: 0.445-0.891]
p=0.0085). The OS benefit was consistent across levels of CD30
expression. Positive outcomes were also observed in key secondary
endpoints, including overall response rate (ORR) and
progression-free survival (PFS).
The safety profile of ADCETRIS in ECHELON-3 was consistent with
its known safety profile as presented in the U.S. prescribing
information. The most frequently reported treatment-emergent
adverse events (TEAEs) Grade 3 or higher for the ADCETRIS versus
placebo arms were: neutropenia (43% vs 28%), thrombocytopenia (25%
vs 19%) and anemia (22% vs 21%). Peripheral sensory neuropathy was
infrequent and low grade for each arm with Grade 3 events of 4% vs
0%.
Detailed data from ECHELON-3 were published in JCO Oncology
Practice on January 7, 2025 and presented at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting.
About ECHELON-3
ECHELON-3 is an ongoing, randomized, double-blind, multicenter
Phase 3 study evaluating ADCETRIS plus lenalidomide and rituximab
versus lenalidomide and rituximab plus placebo in adult patients
with relapsed/refractory or transformed DLBCL, regardless of CD30
expression, who have received two or more prior lines of therapy
and are ineligible for stem cell transplant (HSCT) or CAR-T
therapy. The study also includes patients with hard-to-treat
subtypes with poorer outcomes including double hit/triple hit
lymphoma and patients with transformed disease. Patients may be
ineligible to receive either HSCT or CAR-T therapy due to
co-morbidities or financial, geographic, insurance, manufacturing
issues. In this global study, 230 patients were randomized across
North America, Europe and Asia-Pacific. The primary endpoint is OS
in the intent to treat population, with key secondary endpoints of
PFS and ORR as assessed by investigator. Other secondary endpoints
include complete response rate, duration of response, safety and
tolerability.
About Large B-cell Lymphoma
LBCL accounts for about 1/3 of cases of NHL, a type of cancer
that starts in the lymphocytes and affects immune cells called B
lymphocytes. LBCL occurs most often in older people, with a median
age of 67 at diagnosis. About 60-70% of people have advanced-stage
disease when diagnosed, and up to 40% have disease that relapses or
becomes refractory to initial therapy, and more than 3,500 patients
a year fail two prior lines of therapy and require third-line
therapy.
DLBCL is the most common and aggressive type of LBCL and is
difficult to treat. More than 25,000 cases of DLBCL are diagnosed
each year in the United States, accounting for more than 25% of all
lymphoma cases. DLBCL can develop spontaneously or as a result of
diseases such as chronic lymphocytic lymphoma/small lymphocytic
lymphoma, follicular lymphoma, or marginal zone lymphoma.
About ADCETRIS
More than 55,000 patients have been treated with ADCETRIS in the
U.S. since its first U.S. approval in 2011, and more than 140,000
patients have been treated with ADCETRIS globally.
ADCETRIS is an antibody-drug conjugate (ADC) comprised of a
CD30-directed monoclonal antibody attached by a protease-cleavable
linker to a microtubule disrupting agent, monomethyl auristatin E
(MMAE), utilizing Pfizer's proprietary technology. The ADC employs
a linker system that is designed to be stable in the bloodstream
but to release MMAE upon internalization into CD30-positive tumor
cells.
ADCETRIS is approved in eight indications in the
U.S.:
- Adult patients with relapsed or refractory large B-cell
lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL)
NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell
lymphoma (HGBL), after two or more lines of systemic therapy who
are not eligible for auto-HSCT or chimeric antigen receptor (CAR)
T-cell therapy, in combination with lenalidomide and a rituximab
product (2025)
- Adult patients with previously untreated Stage III/IV classical
Hodgkin lymphoma (cHL) in combination with doxorubicin,
vinblastine, and dacarbazine (2018)
- Pediatric patients 2 years and older with previously untreated
high risk cHL in combination with doxorubicin, vincristine,
etoposide, prednisone and cyclophosphamide (2022)
- Adult patients with cHL at high risk of relapse or progression
as post-autologous hematopoietic stem cell transplantation
(auto-HSCT) consolidation (2015)
- Adult patients with cHL after failure of auto-HSCT or after
failure of at least two prior multi-agent chemotherapy regimens in
patients who are not auto-HSCT candidates (2011)
- Adult patients with previously untreated systemic anaplastic
large cell lymphoma (sALCL) or other CD30-expressing peripheral
T-cell lymphomas (PTCL), including angioimmunoblastic T-cell
lymphoma and PTCL not otherwise specified, in combination with
cyclophosphamide, doxorubicin, and prednisone (2018)
- Adult patients with sALCL after failure of at least one prior
multi-agent chemotherapy regimen. (2011)
- Adult patients with primary cutaneous anaplastic large cell
lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after
prior systemic therapy (2017)
Pfizer and Takeda jointly develop ADCETRIS. Under the terms of
the collaboration agreement, Pfizer has U.S. and Canadian
commercialization rights, and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Pfizer and Takeda are funding
joint development costs for ADCETRIS on a 50:50 basis, except in
Japan where Takeda is solely responsible for development costs.
ADCETRIS® (brentuximab vedotin) for injection U.S. Important
Safety Information
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC
virus infection resulting in PML, and death can occur in
ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary
toxicity (e.g., interstitial infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
Peripheral neuropathy (PN): ADCETRIS causes PN that is
predominantly sensory. Cases of motor PN have also been reported.
ADCETRIS-induced PN is cumulative. Monitor for symptoms such as
hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain, or weakness. Patients experiencing new
or worsening PN may require a delay, change in dose, or
discontinuation of ADCETRIS.
Anaphylaxis and infusion reactions: Infusion-related
reactions (IRR), including anaphylaxis, have occurred with
ADCETRIS. Monitor patients during infusion. If an IRR occurs,
interrupt the infusion and institute appropriate medical
management. If anaphylaxis occurs, immediately and permanently
discontinue the infusion and administer appropriate medical
therapy. Premedicate patients with a prior IRR before subsequent
infusions. Premedication may include acetaminophen, an
antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of
febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1
week) severe neutropenia and Grade 3 or 4 thrombocytopenia or
anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for
adult patients who receive ADCETRIS in combination with
chemotherapy for previously untreated Stage III/IV cHL or
previously untreated PTCL or relapsed or refractory LBCL and
pediatric patients who receive ADCETRIS in combination with
chemotherapy for previously untreated high risk cHL.
Monitor complete blood counts prior to each ADCETRIS dose.
Monitor more frequently for patients with Grade 3 or 4 neutropenia.
Monitor patients for fever. If Grade 3 or 4 neutropenia develops,
consider dose delays, reductions, discontinuation, or G-CSF
prophylaxis with subsequent doses.
Serious infections and opportunistic infections:
Infections such as pneumonia, bacteremia, and sepsis or septic
shock (including fatal outcomes) have been reported in
ADCETRIS-treated patients. Closely monitor patients during
treatment for infections.
Tumor lysis syndrome: Patients with rapidly proliferating
tumor and high tumor burden may be at increased risk. Monitor
closely and take appropriate measures.
Increased toxicity in the presence of severe renal
impairment: The frequency of ≥Grade 3 adverse reactions and
deaths was greater in patients with severe renal impairment. Avoid
use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe
hepatic impairment: The frequency of ≥Grade 3 adverse reactions
and deaths was greater in patients with moderate or severe hepatic
impairment. Avoid use in patients with moderate or severe hepatic
impairment.
Hepatotoxicity: Fatal and serious cases have occurred in
ADCETRIS-treated patients. Cases were consistent with
hepatocellular injury, including elevations of transaminases and/or
bilirubin, and occurred after the first ADCETRIS dose or
rechallenge. Preexisting liver disease, elevated baseline liver
enzymes, and concomitant medications may increase the risk. Monitor
liver enzymes and bilirubin. Patients with new, worsening, or
recurrent hepatotoxicity may require a delay, change in dose, or
discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML
have been reported in ADCETRIS-treated patients. First onset of
symptoms occurred at various times from initiation of ADCETRIS,
with some cases occurring within 3 months of initial exposure. In
addition to ADCETRIS therapy, other possible contributory factors
include prior therapies and underlying disease that may cause
immunosuppression. Consider PML diagnosis in patients with
new-onset signs and symptoms of central nervous system
abnormalities. Hold ADCETRIS if PML is suspected and discontinue
ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of
noninfectious pulmonary toxicity, including pneumonitis,
interstitial lung disease, and acute respiratory distress syndrome,
have been reported. Monitor patients for signs and symptoms,
including cough and dyspnea. In the event of new or worsening
pulmonary symptoms, hold ADCETRIS dosing during evaluation and
until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases
of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
(TEN) have been reported with ADCETRIS. If SJS or TEN occurs,
discontinue ADCETRIS and administer appropriate medical
therapy.
Gastrointestinal (GI) complications: Fatal and serious
cases of acute pancreatitis have been reported. Other fatal and
serious GI complications include perforation, hemorrhage, erosion,
ulcer, intestinal obstruction, enterocolitis, neutropenic colitis,
and ileus. Lymphoma with pre-existing GI involvement may increase
the risk of perforation. In the event of new or worsening GI
symptoms, including severe abdominal pain, perform a prompt
diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset
hyperglycemia, exacerbation of pre-existing diabetes mellitus, and
ketoacidosis (including fatal outcomes) have been reported with
ADCETRIS. Hyperglycemia occurred more frequently in patients with
high body mass index or diabetes. Monitor serum glucose and if
hyperglycemia develops, administer anti-hyperglycemic medications
as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action
and animal studies, ADCETRIS can cause fetal harm. Advise females
of reproductive potential of this potential risk, and to use
effective contraception during ADCETRIS treatment and for 2 months
after the last dose of ADCETRIS. Advise male patients with female
partners of reproductive potential to use effective contraception
during ADCETRIS treatment and for 4 months after the last dose of
ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) in adult patients are
peripheral neuropathy, nausea, fatigue, musculoskeletal pain,
constipation, diarrhea, vomiting, pyrexia, upper respiratory tract
infection, mucositis, abdominal pain, and rash. The most common
laboratory abnormalities (≥20%) in adult patients are decreased
neutrophils, increased creatinine, decreased hemoglobin, decreased
lymphocytes, increased glucose, increased ALT, and increased
AST.
The most common Grade ≥3 adverse reactions (≥5%) in combination
with AVEPC in pediatric patients were neutropenia, anemia,
thrombocytopenia, febrile neutropenia, stomatitis, and
infection.
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to
affect the exposure to monomethyl auristatin E (MMAE). Closely
monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during
ADCETRIS treatment.
Please see the full Prescribing Information, including BOXED
WARNING, for ADCETRIS here. There may be a delay as the
document is updated with the latest information. It will be
available as soon as possible. Please check back for the updated
full information shortly.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in
cancer care. Our industry-leading portfolio and extensive pipeline
includes three core mechanisms of action to attack cancer from
multiple angles, including small molecules, antibody-drug
conjugates (ADCs), and bispecific antibodies, including other
immune-oncology biologics. We are focused on delivering
transformative therapies in some of the world’s most common
cancers, including breast cancer, genitourinary cancer,
hematology-oncology, and thoracic cancers, which includes lung
cancer. Driven by science, we are committed to accelerating
breakthroughs to help people with cancer live better and longer
lives.
About Pfizer: Breakthroughs That Change Patients’
Lives
At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety, and value
in the discovery, development, and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments, and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
biopharmaceutical companies, we collaborate with health care
providers, governments, and local communities to support and expand
access to reliable, affordable health care around the world. For
175 years, we have worked to make a difference for all who rely on
us. We routinely post information that may be important to
investors on our website at www.pfizer.com. In addition, to learn
more, please visit us on www.pfizer.com and follow us on X at
@Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook
at Facebook.com/Pfizer.
Disclosure Notice
The information contained in this release is as of February 12,
2025. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new
information or future events or developments.
This release contains forward-looking information about Pfizer
Oncology and ADCETRIS (brentuximab vedotin), including its
potential benefits, an approval in the U.S. for ADCETRIS in
combination with lenalidomide and rituximab for adults with
relapsed/refractory large B-cell lymphoma and the ongoing
investigational trial for ADCETRIS in combination with lenalidomide
and rituximab, that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
success of ADCETRIS; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical
trials, regulatory submission dates, regulatory approval dates
and/or launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data; the
risk that clinical trial data are subject to differing
interpretations and assessments by regulatory authorities; whether
regulatory authorities will be satisfied with the design of and
results from our clinical studies; whether and when drug
applications may be filed in particular jurisdictions for ADCETRIS
for any potential indications; whether and when any applications
that may be pending or filed for ADCETRIS may be approved by
regulatory authorities, which will depend on myriad factors,
including making a determination as to whether the product's
benefits outweigh its known risks and determination of the
product's efficacy and, if approved, whether ADCETRIS will be
commercially successful; decisions by regulatory authorities
impacting labeling, manufacturing processes, safety and/or other
matters that could affect the availability or commercial potential
of ADCETRIS; uncertainties regarding the impact of COVID-19 on
Pfizer’s business, operations and financial results; and
competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2023 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250207460554/en/
Media Contact: +1 (212) 733-1226 PfizerMediaRelations@pfizer.com
Investor Contact: +1 (212) 733-4848 IR@pfizer.com
Pfizer (NYSE:PFE)
Historical Stock Chart
From Jan 2025 to Feb 2025
Pfizer (NYSE:PFE)
Historical Stock Chart
From Feb 2024 to Feb 2025
