- TIVDAK is a First-in-Class
Antibody-Drug Conjugate Directed to Tissue Factor, a
Protein Expressed
on Cervical Cancer
Cells
- New Monotherapy Approved for
Use in a Cancer
with Limited Treatment
Options
COPENHAGEN, Denmark,
and BOTHELL, Wash.; September 20,
2021 –
Genmab A/S (Nasdaq: GMAB) and Seagen Inc. (Nasdaq: SGEN) today
announced that the U.S. Food and Drug Administration (FDA) has
granted accelerated approval to TIVDAKTM (tisotumab vedotin-tftv),
the first and only approved antibody-drug conjugate (ADC) for the
treatment of adult patients with recurrent or metastatic cervical
cancer with disease progression on or after chemotherapy. TIVDAK is
approved under the FDA’s Accelerated Approval Program based on
tumor response and the durability of the response. Continued
approval may be contingent upon verification and description of
clinical benefit in confirmatory trials.1
“Once recurrent or metastatic cervical cancer progresses, there
is a need for more options for these patients,” said Robert L.
Coleman, M.D., Chief Scientific Officer, US Oncology Research and
lead investigator of the innovaTV 204 clinical trial. “This is an
important development for patients with recurrent or metastatic
cervical cancer.”
In the innovaTV 204 clinical trial, TIVDAK was evaluated in 101
patients with recurrent or metastatic cervical cancer who had
received no more than two prior systemic regimens in the recurrent
or metastatic setting, including at least one prior platinum-based
chemotherapy regimen. Results from the trial showed a 24 percent
confirmed objective response rate (ORR) (95% CI;
15.9-33.3), as assessed by an independent review committee
(IRC) using Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 criteria. The median duration of response (DOR) was 8.3 months
(95% CI; 4.2 to not reached).
The prescribing information for TIVDAK includes a BOXED
WARNING for ocular toxicity, and Warnings for peripheral
neuropathy, hemorrhage, pneumonitis, and embryo-fetal toxicity. The
most common (≥25%) adverse reactions, including laboratory
abnormalities, were hemoglobin decreased (52%), fatigue (50%),
lymphocytes decreased (42%), nausea (41%), peripheral neuropathy
(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%). Please see Important Safety Information below.1
“We are thrilled to see this new treatment approved by the FDA.
We are grateful to have another option for this devastating
disease,” said Tamika Felder, Founder, Cervivor.
“TIVDAK’s approval as a monotherapy in the U.S. is an important
milestone for women with recurrent or metastatic cervical cancer
with disease progression on or after chemotherapy, as they are in
need of a new treatment option and we look forward to making it
available to them,” said Jan van de Winkel, Ph.D., Chief Executive
Officer, Genmab. “The journey towards the approval of TIVDAK
started nearly two decades ago with innovative research by
scientists at Genmab and Seagen and reflects on our purpose of
making an impact in the lives of cancer patients and their
families. Today’s announcement marks Genmab’s evolution into a
fully integrated biotechnology company and we would like to thank
patients, caregivers, investigators and our collaborators for their
participation in our clinical studies.”
“We are pleased with the accelerated approval of TIVDAK,
Seagen’s third FDA-approved antibody-drug conjugate, and fourth
approved medicine. Our mission at Seagen is to develop medicines
that make a difference for people impacted by cancer,” said Roger
Dansey, M.D., Chief Medical Officer, Seagen.
The Biologics License Application (BLA) for TIVDAK was submitted
in February 2021 and accepted with Priority Review in April 2021.
The submission was based on the results of the innovaTV 204
trial.
The FDA’s Accelerated Approval Program allows for approval of a
medicine based on a surrogate endpoint that is reasonably likely to
predict clinical benefit, if the medicine fills an unmet medical
need for a serious condition. A global, randomized phase 3 clinical
trial (innovaTV 301) is underway and is also intended to support
global registrations.
About Cervical CancerIt is estimated that in
2021, more than 14,480 new cases of invasive cervical cancer will
be diagnosed in the U.S., and 4,290 women will die from the
disease.2 Cervical cancer remains one of the leading causes of
cancer death in women globally, with over 311,000 women dying of
the disease in 2018.3
About the innovaTV 204 TrialThe innovaTV 204
trial (NCT03438396/GOG-3023/ENGOT-cx6) is an open-label,
multicenter, single-arm Phase 2 trial that evaluated tisotumab
vedotin in 101 patients with recurrent or metastatic cervical
cancer who had received no more than two prior systemic regimens in
the recurrent or metastatic setting, including at least one prior
platinum-based chemotherapy regimen. Patients were excluded if they
had active ocular surface disease, any prior episode of cicatricial
conjunctivitis or Stevens-Johnson syndrome, Grade ≥2 peripheral
neuropathy or known coagulation defects leading to an increased
risk of bleeding. The main efficacy outcome measures were confirmed
ORR per RECIST v1.1 as assessed by an IRC and DOR.1
The study was conducted by Genmab in collaboration with Seagen,
European Network of Gynaecological Oncological Trial Groups (ENGOT)
and the GOG Foundation, Inc. (GOG). For more information about the
phase 2 innovaTV 204 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 ADC composed of Genmab’s human
monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC
technology that utilizes a protease-cleavable linker that
covalently attaches the microtubule-disrupting agent monomethyl
auristatin E (MMAE) to the antibody. Nonclinical data suggests that
the anticancer activity of TIVDAK 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,
TIVDAK also mediates antibody-dependent cellular phagocytosis and
antibody-dependent cellular cytotoxicity.1
TIVDAK (tisotumab
vedotin-tftv) for
injection, for intravenous
use, 40 mg
Important Safety Information
BOXED WARNING: OCULAR
TOXICITYTIVDAK 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. 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.
Monitor patients for signs and symptoms of neuropathy. For new
or worsening PN, withhold, dose reduce, or permanently discontinue
TIVDAK based on the severity of PN.
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 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: Severe, life-threatening, or fatal
pneumonitis 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 indicative of
pneumonitis. 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.
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 Genmab Genmab is an international
biotechnology company with a core purpose to improve the lives of
people with cancer. For more than 20 years, Genmab’s vision to
transform cancer treatment has driven its passionate, innovative
and collaborative teams to invent next-generation antibody
technology platforms and leverage translational research and data
sciences, fueling multiple differentiated cancer treatments that
make an impact on people’s lives. To develop and deliver novel
therapies to patients, Genmab has formed 20+ strategic partnerships
with biotechnology and pharmaceutical companies. Genmab’s
proprietary pipeline includes bispecific T-cell engagers,
next-generation immune checkpoint modulators, effector function
enhanced antibodies and antibody-drug conjugates.
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 Seagen Seagen is a
global biotechnology company that discovers, develops and
commercializes transformative cancer medicines to make a meaningful
difference in people’s lives. Seagen is headquartered in the
Seattle, Washington area, and has locations in California, Canada,
Switzerland and the European Union. For more information on our
marketed products and robust pipeline, visit www.seagen.com and
follow @SeagenGlobal on Twitter.
About the Seagen and
Genmab CollaborationTisotumab vedotin is being
co-developed by Genmab and Seagen, under an agreement in which the
companies share costs and profits for the product on a 50:50
basis.
Genmab A/S
Contacts:For
Media: Marisol
Peron, Senior Vice President, Global Investor Relations &
CommunicationsT: +1 609 524 0065; E: mmp@genmab.com
For Investor Relations: Andrew Carlsen, Vice President, Head of
Investor RelationsT: +45 3377 9558; E: acn@genmab.com
Seagen Contacts:For Media:David
CaouetteVice President, Corporate Communications(310)
430-3476dcaouette@seagen.com
For Investor Relations:Peggy PinkstonSenior Vice President,
Investor Relations(425) 527-4160ppinkston@seagen.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. TIVDAKTM and the TIVDAK logo are trademarks
owned by Seagen Inc.
Seagen Forward Looking
Statements Certain of the statements made in this press
release are forward looking, such as those, among others, relating
to the continued FDA approval of TIVDAK (tisotumab vedotin-tftv)
for the treatment of adult patients with recurrent or metastatic
cervical cancer with disease progression on or after chemotherapy;
the conduct of an ongoing randomized phase 3 clinical trial
(innovaTV 301) intended to verify the clinical benefit of TIVDAK
and support global registrations; and the therapeutic potential of
TIVDAK, including its efficacy, safety and therapeutic uses. Actual
results or developments may differ materially from those projected
or implied in these forward-looking statements. Factors that may
cause such a difference include the possibility that innovaTV 301
and subsequent clinical trials may fail to establish sufficient
efficacy; that adverse events or safety signals may occur; that
utilization and adoption of TIVDAK by prescribing physicians may be
limited by the availability and extent of reimbursement and other
factors; and that adverse regulatory actions may occur. More
information about the risks and uncertainties faced by Seagen is
contained under the caption “Risk Factors” included in the
Company’s Quarterly Report on Form 10-Q for the quarter ended June
30, 2021 filed with the Securities and Exchange Commission. Seagen
disclaims any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise, except as required by law.
References1 TIVDAK [package insert]. Bothell,
WA: Seagen, Inc.2 Cancer Stat Facts: Cervical Cancer. National
Cancer Institute website.
https://seer.cancer.gov/statfacts/html/cervix.html. Accessed
September 16, 2021.3 Bray F, Ferlay J, Soerjomataram I, et al.
Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and
Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J
Clin 2018;0: 1-31.
# # #
- 200921_CA62_innovaTV 204 Approval
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