– Submission based on positive results from
global phase 3 study demonstrating overall survival benefit of
TIVDAK over chemotherapy –
Pfizer Inc. (NYSE: PFE) and Genmab A/S (Nasdaq: GMAB) announced
today that the U.S. Food and Drug Administration (FDA) has accepted
the supplemental Biologics License Application (sBLA) seeking to
convert the accelerated approval of TIVDAK® (tisotumab
vedotin-tftv) to full approval, for the treatment of patients with
recurrent or metastatic cervical cancer with disease progression on
or after first-line therapy. The application has been granted
Priority Review with a Prescription Drug User Fee Act (PDUFA) goal
date of May 9, 2024.
“The Phase 3 innovaTV 301 trial demonstrated a favorable
benefit/risk profile, including improvement in overall survival,
and adds to the overall data supporting TIVDAK as a treatment
option for people with recurrent and metastatic cervical cancer who
have limited treatment options,” said Roger Dansey, M.D., Chief
Development Officer, Oncology at Pfizer. “The FDA acceptance of our
sBLA for review is important progress toward continuing to offer an
option that can extend the lives of more adults with cervical
cancer.”
The sBLA is supported by efficacy and safety data from the
global, randomized, Phase 3 innovaTV 301 trial (NCT04697628), in
which TIVDAK demonstrated superior overall survival (OS),
progression-free survival (PFS) and confirmed objective response
rate (ORR), as assessed by the investigator, in patients with
previously treated recurrent or metastatic cervical cancer compared
to chemotherapy. The safety profile of TIVDAK in innovaTV 301 was
consistent with its known safety profile as presented in the U.S.
prescribing information. In October 2023, results from the innovaTV
301 study were presented during a Presidential Symposium at the
European Society of Medical Oncology (ESMO) Congress.
The U.S. Prescribing Information for TIVDAK includes a BOXED
WARNING for Ocular Toxicity as well as the following
Warnings and Precautions: peripheral neuropathy, hemorrhage,
pneumonitis, severe cutaneous adverse reactions, and embryo-fetal
toxicity. Please see below for additional Important Safety
Information.
“Therapeutic options for metastatic cervical cancer that not
only demonstrate a survival advantage but also include a novel
approach to treating this condition are needed,” said Jan van de
Winkel, Ph.D., Chief Executive Officer at Genmab. “This milestone
underscores our commitment to continuing to deliver TIVDAK as a
treatment option to women in the U.S. diagnosed with cervical
cancer whose disease has progressed after first-line
treatment.”
TIVDAK was granted accelerated approval in the U.S. by the FDA
in September 2021. The accelerated approval is based on tumor
response and durability of response from the innovaTV 204 pivotal
Phase 2 single-arm clinical trial evaluating TIVDAK as monotherapy
in patients with previously treated recurrent or metastatic
cervical cancer. The data from innovaTV 301 will support global
regulatory submissions.
About Cervical Cancer Cervical cancer remains a disease
with high unmet need despite advances in effective vaccination and
screening practices to prevent and diagnose pre-/early-stage
cancers for curative treatment. Recurrent and/or metastatic
cervical cancer is a particularly devastating and mostly incurable
disease; up to 15 percent of adults with cervical cancer are
diagnosed with metastatic disease at diagnosis1,2 and, for adults
diagnosed at earlier stages who receive treatment, up to 31.5
percent will experience disease recurrence.3 It was estimated that,
in 2023, more than 13,960 new cases of invasive cervical cancer
were diagnosed in the U.S. and 4,310 adults would die from the
disease.4
About the innovaTV 301 Trial The innovaTV 301 trial
(NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial
evaluating (tisotumab vedotin-tftv) versus investigator’s choice of
chemotherapy alone (topotecan, vinorelbine, gemcitabine,
irinotecan, or pemetrexed) in 502 randomized patients with
recurrent or metastatic cervical cancer who received one or two
prior systemic regimens in the recurrent or metastatic setting.
Patients with recurrent or metastatic cervical cancer with
squamous cell, adenocarcinoma, or adenosquamous histology, and
disease progression during or after treatment with chemotherapy
doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are
included. The primary endpoint is overall survival. The main
secondary outcomes are progression-free survival, confirmed
objective response rate, time to response, and duration of
response, as assessed by the investigator, as well as safety and
quality of life outcomes.
The study was conducted by Seagen, recently acquired by Pfizer,
in collaboration with Genmab, European Network of Gynaecological
Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the
Gynecologic Oncology Group (GOG) Foundation (study number GOG
3057), as well as other global gynecological oncology cooperative
groups. For more information about the Phase 3 innovaTV 301
clinical trial and other clinical trials with tisotumab vedotin,
please visit www.clinicaltrials.gov.
About TIVDAK® (tisotumab vedotin-tftv) TIVDAK® (tisotumab
vedotin-tftv) is an antibody-drug conjugate (ADC) composed of
Genmab’s human monoclonal antibody directed to tissue factor (TF)
and Pfizer’s ADC technology that utilizes a protease-cleavable
linker that covalently attaches the microtubule-disrupting agent
monomethyl auristatin E (MMAE) to the antibody. Determination of TF
expression is not required. Nonclinical data suggest that the
anticancer activity of tisotumab vedotin-tftv is due to the binding
of the ADC to TF-expressing cancer cells, followed by
internalization of the ADC-TF complex, and release of MMAE via
proteolytic cleavage. MMAE disrupts the microtubule network of
actively dividing cells, leading to cell cycle arrest and apoptotic
cell death. In vitro, tisotumab vedotin-tftv also mediates
antibody-dependent cellular phagocytosis and antibody-dependent
cellular cytotoxicity.
Indication TIVDAK is indicated in the U.S. for the
treatment of adult patients with recurrent or metastatic cervical
cancer with disease progression on or after chemotherapy.
This indication is approved under accelerated approval based on
tumor response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
Important Safety Information
BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and
conjunctiva resulting in changes in vision, including severe vision
loss, and corneal ulceration. Conduct an ophthalmic exam at
baseline, prior to each dose, and as clinically indicated. Adhere
to premedication and required eye care before, during, and after
infusion. Withhold TIVDAK until improvement and resume, reduce the
dose, or permanently discontinue, based on severity.
WARNINGS AND PRECAUTIONS
Ocular adverse reactions occurred in 60% of patients with
cervical cancer treated with TIVDAK across clinical trials. The
most common were conjunctival adverse reactions (40%), dry eye
(29%), corneal adverse reactions (21%), and blepharitis (8%). Grade
3 ocular adverse reactions occurred in 3.8% of patients, including
severe ulcerative keratitis in 3.2% of patients. One patient
experienced ulcerative keratitis with perforation requiring corneal
transplantation. Cases of symblepharon were reported in patients
with other tumor types treated with TIVDAK at the recommended
dose.
In innovaTV 204, 4% of patients experienced visual acuity
changes to 20/50 or worse including 1% of patients who experienced
a visual acuity change to 20/200. Of the patients who experienced
decreased visual acuity to 20/50 or worse, 75% resolved, including
the patient who experienced decreased visual acuity to 20/200.
Refer patients to an eye care provider for an ophthalmic exam,
including visual acuity and slit lamp exam, at baseline, prior to
each dose, and as clinically indicated. Adhere to premedication and
required eye care to reduce the risk of ocular adverse reactions.
Promptly refer patients to an eye care provider for any new or
worsening ocular signs and symptoms. Withhold dose, reduce the
dose, or permanently discontinue TIVDAK based on the severity of
the adverse reaction.
Peripheral Neuropathy (PN) occurred in 42% of cervical
cancer patients treated with TIVDAK across clinical trials; 8% of
patients experienced Grade 3 PN. PN adverse reactions included
peripheral neuropathy (20%), peripheral sensory neuropathy (11%),
peripheral sensorimotor neuropathy (5%), motor neuropathy (3%),
muscular weakness (3%), and demyelinating peripheral polyneuropathy
(1%). One patient with another tumor type treated with TIVDAK at
the recommended dose developed Guillain-Barré syndrome.
Hemorrhage occurred in 62% of cervical cancer patients
treated with TIVDAK across clinical trials. The most common all
grade hemorrhage adverse reactions were epistaxis (44%), hematuria
(10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in
5% of patients.
Monitor patients for signs and symptoms of hemorrhage. For
patients experiencing pulmonary or central nervous system (CNS)
hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage
in any other location, withhold until bleeding has resolved, blood
hemoglobin is stable, there is no bleeding diathesis that could
increase the risk of continuing therapy, and there is no anatomical
or pathologic condition that can increase the risk of hemorrhage
recurrence. After resolution, either resume treatment or
permanently discontinue TIVDAK.
Pneumonitis that is severe, life-threatening, or fatal
can occur in patients treated with antibody-drug conjugates
containing vedotin, including TIVDAK. Among patients with cervical
cancer treated with TIVDAK across clinical trials, 2 patients
(1.3%) experienced pneumonitis, including 1 patient who had a fatal
outcome.
Monitor patients for pulmonary symptoms of pneumonitis. Symptoms
may include hypoxia, cough, dyspnea or interstitial infiltrates on
radiologic exams. Infectious, neoplastic, and other causes for
symptoms should be excluded through appropriate investigations.
Withhold TIVDAK for patients who develop persistent or recurrent
Grade 2 pneumonitis and consider dose reduction. Permanently
discontinue TIVDAK in all patients with Grade 3 or 4
pneumonitis.
Severe cutaneous adverse reactions, including events of
fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur
in patients treated with TIVDAK.
Monitor patients for signs or symptoms of severe cutaneous
adverse reactions, which include target lesions, worsening skin
reactions, blistering or peeling of the skin, painful sores in
mouth, nose, throat, or genital area, fever or flu-like symptoms,
and swollen lymph nodes. If signs or symptoms of severe cutaneous
adverse reactions occur, withhold TIVDAK until the etiology of the
reaction has been determined. Early consultation with a specialist
is recommended to ensure greater diagnostic accuracy and
appropriate management. Permanently discontinue TIVDAK for
confirmed Grade 3 or 4 severe cutaneous adverse reactions,
including SJS.
Embryo-fetal toxicity: TIVDAK can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risk to a fetus. Advise females of reproductive potential to use
effective contraception during treatment with TIVDAK and for 2
months after the last dose. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with TIVDAK and for 4 months after the last
dose.
Adverse Reactions
Serious adverse reactions occurred in 43% of patients; the most
common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN,
sepsis, constipation, and pyrexia (each 3%). Fatal adverse
reactions occurred in 4% of patients who received TIVDAK, including
septic shock, pneumonitis, sudden death, and multisystem organ
failure (each 1%).
Adverse reactions leading to permanent discontinuation occurred
in 13% of patients receiving TIVDAK; the most common (≥3%) were PN
(5%) and corneal adverse reactions (4%). Adverse reactions leading
to dose interruption occurred in 47% of patients; the most common
(≥3%) were PN (8%), conjunctival adverse reactions (4%), and
hemorrhage (4%). Adverse reactions leading to dose reduction
occurred in 23% of patients; the most common (≥3%) were
conjunctival adverse reactions (9%) and corneal adverse reactions
(8%).
The most common (≥25%) adverse reactions, including laboratory
abnormalities, were hemoglobin decreased (52%), fatigue (50%),
lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia
(39%), epistaxis (39%), conjunctival adverse reactions (37%),
hemorrhage (32%), leukocytes decreased (30%), creatinine increased
(29%), dry eye (29%), prothrombin international normalized ratio
increased (26%), activated partial thromboplastin time prolonged
(26%), diarrhea (25%), and rash (25%).
Drug Interactions
Strong CYP3A4 inhibitors: Concomitant use with strong
CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E
(MMAE) exposure, which may increase the risk of TIVDAK adverse
reactions. Closely monitor patients for TIVDAK adverse
reactions.
Use in Specific Populations
Moderate or severe hepatic impairment: MMAE exposure and
adverse reactions are increased. Avoid use.
Lactation: Advise lactating women not to breastfeed
during TIVDAK treatment and for at least 3 weeks after the last
dose.
Please see full prescribing information, including BOXED
WARNING for TIVDAK here.
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 game-changing mechanisms
of action to attack cancer from multiple angles, including
antibody-drug conjugates (ADCs), small molecules, bispecifics and
other immunotherapies. We are focused on delivering transformative
therapies in some of the world’s most common cancers, including
breast cancer, genitourinary cancer and hematologic malignancies,
as well as melanoma, gastrointestinal, gynecological and thoracic
cancers, which includes lung cancer. Driven by science, we are
committed to accelerating breakthroughs to extend and improve
patients’ lives. 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 (Twitter) at @Pfizer and @Pfizer News, LinkedIn,
YouTube and like us on Facebook at Facebook.com/Pfizer.
About Genmab Genmab is an international biotechnology
company with a core purpose guiding its unstoppable team to strive
towards improving the lives of patients through innovative and
differentiated antibody therapeutics. For more than 20 years, its
passionate, innovative and collaborative team has invented
next-generation antibody technology platforms and leveraged
translational research and data sciences, which has resulted in a
proprietary pipeline including bispecific T-cell engagers,
next-generation immune checkpoint modulators, effector function
enhanced antibodies and antibody-drug conjugates. To help develop
and deliver novel antibody therapies to patients, Genmab has formed
20+ strategic partnerships with biotechnology and pharmaceutical
companies. By 2030, Genmab’s vision is to transform the lives of
people with cancer and other serious diseases with
Knock-Your-Socks-Off (KYSO™) antibody medicines.
Established in 1999, Genmab is headquartered in Copenhagen,
Denmark with locations in Utrecht, the Netherlands, Princeton, New
Jersey, U.S. and Tokyo, Japan. For more information, please visit
Genmab.com and follow us on Twitter.com/Genmab.
About the Pfizer and Genmab Collaboration Tisotumab
vedotin is co-owned by Genmab and Pfizer, under an agreement in
which the companies share costs and profits for the product on a
50:50 basis.
Pfizer Disclosure Notice
The information contained in this release is as of January 9,
2024. 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 TIVDAK® (tisotumab vedotin-tftv), including potential
to convert the accelerated approval of TIVDAK to full approval,
potential benefits and plans for data from innovaTV 301 to support
global regulatory submissions, 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 TIVDAK; 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
TIVDAK; whether and when any applications that may be pending or
filed for TIVDAK may be approved by regulatory authorities
(including the sBLA seeking to convert the accelerated approval of
TIVDAK to full approval, for the treatment of patients with
recurrent or metastatic cervical cancer with disease progression on
or after first-line therapy), 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 TIVDAK 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 TIVDAK; whether the collaboration between Pfizer and Genmab will
be successful; 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, 2022 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.
Genmab Forward Looking Statements This Company
Announcement contains forward looking statements. The words
“believe”, “expect”, “anticipate”, “intend” and “plan” and similar
expressions identify forward looking statements. Actual results or
performance may differ materially from any future results or
performance expressed or implied by such statements. The important
factors that could cause our actual results or performance to
differ materially include, among others, risks associated with
pre-clinical and clinical development of products, uncertainties
related to the outcome and conduct of clinical trials including
unforeseen safety issues, uncertainties related to product
manufacturing, the lack of market acceptance of our products, our
inability to manage growth, the competitive environment in relation
to our business area and markets, our inability to attract and
retain suitably qualified personnel, the unenforceability or lack
of protection of our patents and proprietary rights, our
relationships with affiliated entities, changes and developments in
technology which may render our products or technologies obsolete,
and other factors. For a further discussion of these risks, please
refer to the risk management sections in Genmab’s most recent
financial reports, which are available on www.genmab.com and the
risk factors included in Genmab’s most recent Annual Report on Form
20-F and other filings with the U.S. Securities and Exchange
Commission (SEC), which are available at www.sec.gov. Genmab does
not undertake any obligation to update or revise forward looking
statements in this Company Announcement nor to confirm such
statements to reflect subsequent events or circumstances after the
date made or in relation to actual results, unless required by
law.
Genmab A/S and/or its subsidiaries own the following trademarks:
Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the
Y-shaped Genmab logo®; HuMax®; DuoBody®; HexaBody®; DuoHexaBody®
and HexElect®.
Category: Medicines
__________________________ 1 National Cancer Institute. SEER
Cancer Stat Facts: Cervical Cancer. 2023.
https://seer.cancer.gov/statfacts/html/cervix.html 2 McLachlan J,
Boussios S, Okines A, et al. The impact of systemic therapy beyond
first-line treatment for advanced cervical cancer. Clin Oncol (R
Coll Radiol). 2017;29(3):153-60. 3 de Foucher T, Bendifallah S,
Ouldamer L, et al. Patterns of recurrence and prognosis in locally
advanced FIGO stage IB2 to IIB cervical cancer: retrospective
multicentre study from the FRANCOGYN Group. Eur J Surg Oncol.
2019;45:659–665. doi: 10.1016/j.ejso.2018.11.014. 4 Key Statistics
for Cervical Cancer. American Cancer Society. Atlanta, GA. 2023.
https://www.cancer.org/cancer/types/cervical-cancer/about/key-statistics.html
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240109858951/en/
INVESTORS & MEDIA
Pfizer: For Media: PfizerMediaRelations@Pfizer.com
+1 (212) 733-1226
For Investor Relations: IR@Pfizer.com +1 (212) 733-4848
Genmab A/S: For Media: David Freundel Senior Director,
Communications & Corporate Affairs (609) 613-0504
dafr@genmab.com
For Investor Relations: Andrew Carlsen Vice President, Head of
Investor Relations +45 3377-9558 acn@genmab.com
Genmab AS (NASDAQ:GMAB)
過去 株価チャート
から 5 2024 まで 6 2024
Genmab AS (NASDAQ:GMAB)
過去 株価チャート
から 6 2023 まで 6 2024