Inc. (KRX:068270) and Teva
Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced
that the U.S. Food and Drug Administration (FDA) has approved HERZUMA®
(trastuzumab-pkrb), a HER2/neu receptor antagonist biosimilar to
HERCEPTIN®1 (trastuzumab) for the following indications:
Adjuvant Breast Cancer of HER2 overexpressing node positive or node
negative (ER/PR negative or with one high risk feature) breast cancer
as part of a treatment regimen consisting of doxorubicin,
cyclophosphamide, and either paclitaxel or docetaxel
as part of a treatment regimen with docetaxel and carboplatin
Metastatic Breast Cancer
in combination with paclitaxel for first-line treatment of
HER2-overexpressing metastatic breast cancer
as a single agent for treatment of HER2-overexpressing breast
cancer in patients who have received one or more chemotherapy
regimens for metastatic disease.
In these indications, patients should be selected for therapy based on
an FDA-approved companion diagnostic for a trastuzumab product
“Biosimilars are of growing importance to the oncology community and the
approval of HERZUMA may provide more patients access to this important
therapy,” stated Woosung Kee, Chief Executive Officer of Celltrion.
“This is our second oncology biosimilar approval in the United States in
the past month, which reinforces the goal for all of our approved
products -- providing broader treatment options for patients and the
providers who treat them.”
HERZUMA meets the FDA’s rigorous standards as a biosimilar to the
reference product for the approved indications based on a totality of
evidence. The FDA approval is based on a review of a comprehensive data
package inclusive of foundational analytical similarity data,
nonclinical data, clinical pharmacology, immunogenicity, clinical
efficacy and safety data. The results of the clinical development
program for HERZUMA demonstrated that there were no clinically
meaningful differences in purity, potency and safety between HERZUMA and
HERCEPTIN for the treatment of HER2-overexpressing breast cancer for the
“We are excited about building Teva’s presence in biosimilars,” said
Brendan O’Grady, Executive Vice President and Head of North America
Commercial at Teva. “The addition of HERZUMA to our biosimilars
portfolio will allow us to leverage our strengths from Oncology and
Trastuzumab products have a Boxed Warning which states that treatment
with trastuzumab may be associated with cardiomyopathy, infusion
reactions, pulmonary toxicity and embryo-fetal toxicity. Please see the
full Boxed Warning and additional Important Safety Information in this
release and accompanying Prescribing Information.
Celltrion and Teva Pharmaceutical Industries Ltd. entered into an
exclusive partnership in October 2016 to commercialize HERZUMA in the
U.S. and Canada.
Important Safety Information and Boxed Warnings
WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL
TOXICITY, AND PULMONARY TOXICITY
Cardiomyopathy - Administration of trastuzumab products can
result in sub-clinical and clinical cardiac failure. The incidence
and severity was highest in patients receiving trastuzumab with
anthracycline- containing chemotherapy regimens.
Evaluate left ventricular function in all patients prior to and
during treatment with HERZUMA. Discontinue HERZUMA treatment in
patients receiving adjuvant therapy and withhold HERZUMA in
patients with metastatic disease for clinically significant
decrease in left ventricular function.
Infusion Reactions; Pulmonary Toxicity - Administration of
trastuzumab products can result in serious and fatal infusion
reactions and pulmonary toxicity. Symptoms usually occur during or
within 24 hours of HERZUMA administration. Interrupt HERZUMA
infusion for dyspnea or clinically significant hypotension.
Monitor patients until symptoms completely resolve. Discontinue
HERZUMA for anaphylaxis, angioedema, interstitial pneumonitis, or
acute respiratory distress syndrome.
Embryo Fetal Toxicity - Exposure to trastuzumab products
during pregnancy can result in oligohydramnios and oligohydramnios
sequence manifesting as pulmonary hypoplasia, skeletal
abnormalities, and neonatal death. Advise patients of these risks
and the need for effective contraception.
Trastuzumab products can cause left ventricular cardiac dysfunction,
arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy,
and cardiac death. Trastuzumab products can also cause asymptomatic
decline in left ventricular ejection fraction (LVEF).
There is a 4–6-fold increase in the incidence of symptomatic
myocardial dysfunction among patients receiving trastuzumab products
as a single agent or in combination therapy compared with those not
receiving trastuzumab products. The highest absolute incidence occurs
when a trastuzumab product is administered with an anthracycline.
Withhold HERZUMA for ≥ 16% absolute decrease in LVEF from
pre-treatment values or an LVEF value below institutional limits of
normal and ≥ 10% absolute decrease in LVEF from pretreatment values.
The safety of continuation or resumption of HERZUMA in patients with
trastuzumab product-induced left ventricular cardiac dysfunction has
not been studied.
Patients who receive anthracycline after stopping HERZUMA may also be
at increased risk of cardiac dysfunction.
Conduct thorough cardiac assessment, including history, physical
examination, and determination of LVEF by echocardiogram or MUGA scan.
The following schedule is recommended:
Baseline LVEF measurement immediately prior to initiation of
LVEF measurements every 3 months during and upon completion of
Repeat LVEF measurement at 4 week intervals if HERZUMA is withheld
for significant left ventricular cardiac dysfunction.
LVEF measurements every 6 months for at least 2 years following
completion of HERZUMA as a component of adjuvant therapy.
Infusion reactions consist of a symptom complex characterized by fever
and chills, and on occasion included nausea, vomiting, pain (in some
cases at tumor sites), headache, dizziness, dyspnea, hypotension,
rash, and asthenia.
In post-marketing reports, serious and fatal infusion reactions have
been reported. Severe reactions, which include bronchospasm,
anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually
reported during or immediately following the initial infusion.
However, the onset and clinical course were variable, including
progressive worsening, initial improvement followed by clinical
deterioration, or delayed post-infusion events with rapid clinical
deterioration. For fatal events, death occurred within hours to days
following a serious infusion reaction.
Interrupt HERZUMA infusion in all patients experiencing dyspnea,
clinically significant hypotension, and intervention of medical
therapy administered (which may include epinephrine, corticosteroids,
diphenhydramine, bronchodilators, and oxygen). Patients should be
evaluated and carefully monitored until complete resolution of signs
and symptoms. Permanent discontinuation should be strongly considered
in all patients with severe infusion reactions.
There are no data regarding the most appropriate method of
identification of patients who may safely be retreated with
trastuzumab products after experiencing a severe infusion reaction.
Prior to resumption of trastuzumab infusion, the majority of patients
who experienced a severe infusion reaction were pre-medicated with
antihistamines and/or corticosteroids. While some patients tolerated
trastuzumab infusions, others had recurrent severe infusion reactions
Trastuzumab products can cause fetal harm when administered to a
pregnant woman. In post marketing reports, use of trastuzumab during
pregnancy resulted in cases of oligohydramnios and oligohydramnios
sequence manifesting as pulmonary hypoplasia, skeletal abnormalities,
and neonatal death.
Verify the pregnancy status of females of reproductive potential prior
to the initiation of HERZUMA. Advise pregnant women and females of
reproductive potential that exposure to HERZUMA during pregnancy or
within 7 months prior to conception can result in fetal harm. Advise
females of reproductive potential to use effective contraception
during treatment and for 7 months following the last dose of HERZUMA.
Trastuzumab product use can result in serious and fatal pulmonary
toxicity. Pulmonary toxicity includes dyspnea, interstitial
pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic
pulmonary edema, pulmonary insufficiency and hypoxia, acute
respiratory distress syndrome, and pulmonary fibrosis. Such events can
occur as sequelae of infusion reactions.
Patients with symptomatic intrinsic lung disease or with extensive
tumor involvement of the lungs, resulting in dyspnea at rest, appear
to have more severe toxicity.
Exacerbation of Chemotherapy-Induced Neutropenia
In randomized, controlled clinical trials, the per-patient incidences
of NCI-CTC Grade 3 to 4 neutropenia and of febrile neutropenia were
higher in patients receiving trastuzumab in combination with
myelosuppressive chemotherapy as compared to those who received
chemotherapy alone. The incidence of septic death was similar among
patients who received trastuzumab and those who did not.
Adjuvant Breast Cancer - Most common adverse reactions (≥5%)
are headache, diarrhea, nausea, and chills.
Metastatic Breast Cancer- Most common adverse reactions (≥ 10%)
are fever, chills, headache, infection, congestive heart failure,
insomnia, cough, and rash.
Please click here
for full Prescribing Information for HERZUMA.
1 HERCEPTIN® is a registered trademark of
About Celltrion, Inc.
Headquartered in Incheon, Korea, Celltrion is a leading
biopharmaceutical company, specializing in research, development and
manufacturing of biosimilar and innovative drugs. Celltrion strives to
provide more affordable biosimilar mAbs to patients who previously had
limited access to advanced therapeutics. Celltrion received FDA and EC’s
approval for Inflectra® and Remsima®,
respectively, which is the world’s first mAb biosimilar to receive
approval from a regulatory agency in a developed country. For more
information, visit www.celltrion.com.
Teva Pharmaceutical Industries Ltd. is a global leader in generic
medicines, with innovative treatments in select areas, including CNS,
pain and respiratory. We deliver high-quality generic products and
medicines in nearly every therapeutic area to address unmet patient
needs. We have an established presence in generics, specialty, OTC and
API, building on more than a century-old legacy, with a fully integrated
R&D function, strong operational base and global infrastructure and
scale. We strive to act in a socially and environmentally responsible
way. Headquartered in Israel, with production and research facilities
around the globe, we employ 45,000 professionals, committed to improving
the lives of millions of patients. Learn more at www.tevapharm.com.
Teva Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995
regarding HERZUMA®, which are based on
management’s current beliefs and expectations and are subject to
substantial risks and uncertainties, both known and unknown, that could
cause our future results, performance or achievements to differ
significantly from that expressed or implied by such forward-looking
statements. Important factors that could cause or contribute to such
differences include risks relating to:
the uncertainty of commercial success of HERZUMA, including
the successful launch of the product;
Our ability to successfully challenge third party's
intellectual property that may apply to HERZUMA;
our ability to successfully compete in the marketplace, including:
that we are substantially dependent on our generic products;
competition for our specialty products, especially COPAXONE®,
our leading medicine, which faces competition from existing and
potential additional generic versions and orally-administered
alternatives; competition from companies with greater resources and
capabilities; efforts of pharmaceutical companies to limit the use of
generics including through legislation and regulations; consolidation
of our customer base and commercial alliances among our customers; the
increase in the number of competitors targeting generic opportunities
and seeking U.S. market exclusivity for generic versions of
significant products; price erosion relating to our products, both
from competing products and increased regulation; delays in launches
of new products and our ability to achieve expected results from
investments in our product pipeline; our ability to take advantage of
high-value opportunities; the difficulty and expense of obtaining
licenses to proprietary technologies; and the effectiveness of our
patents and other measures to protect our intellectual property rights;
our substantially increased indebtedness and significantly
decreased cash on hand, which may limit our ability to incur
additional indebtedness, engage in additional transactions or make new
investments, may result in a further downgrade of our credit ratings;
and our inability to raise debt or borrow funds in amounts or on terms
that are favorable to us;
our business and operations in general, including: failure to
effectively execute our restructuring plan announced in December 2017;
uncertainties related to, and failure to achieve, the potential
benefits and success of our new senior management team and
organizational structure; harm to our pipeline of future products due
to the ongoing review of our R&D programs; our ability to develop and
commercialize additional pharmaceutical products; potential additional
adverse consequences following our resolution with the U.S. government
of our FCPA investigation; compliance with sanctions and other trade
control laws; manufacturing or quality control problems, which may
damage our reputation for quality production and require costly
remediation; interruptions in our supply chain; disruptions of our or
third party information technology systems or breaches of our data
security; the failure to recruit or retain key personnel; variations
in intellectual property laws that may adversely affect our ability to
manufacture our products; challenges associated with conducting
business globally, including adverse effects of political or economic
instability, major hostilities or terrorism; significant sales to a
limited number of customers in our U.S. market; our ability to
successfully bid for suitable acquisition targets or licensing
opportunities, or to consummate and integrate acquisitions; and our
prospects and opportunities for growth if we sell assets;
compliance, regulatory and litigation matters, including: costs and
delays resulting from the extensive governmental regulation to which
we are subject; the effects of reforms in healthcare regulation and
reductions in pharmaceutical pricing, reimbursement and coverage;
governmental investigations into sales and marketing practices;
potential liability for patent infringement; product liability claims;
increased government scrutiny of our patent settlement agreements;
failure to comply with complex Medicare and Medicaid reporting and
payment obligations; and environmental risks;
other financial and economic risks, including: our exposure to
currency fluctuations and restrictions as well as credit risks;
potential impairments of our intangible assets; potential significant
increases in tax liabilities; and the effect on our overall effective
tax rate of the termination or expiration of governmental programs or
tax benefits, or of a change in our business;
and other factors discussed in our Annual Report on Form 10-K for
the year ended December 31, 2017, including in the section captioned
“Risk Factors,” and in our other filings with the U.S. Securities and
Exchange Commission, which are available at www.sec.gov
Forward-looking statements speak only as of the date on which they are
made, and we assume no obligation to update or revise any
forward-looking statements or other information contained herein,
whether as a result of new information, future events or otherwise.
You are cautioned not to put undue reliance on these forward-looking