Multiple genes associated with potential therapeutic effects
expressed differently: Gene expression analysis provides insight into
variability
JERUSALEM--(BUSINESS WIRE)--Jan. 13, 2014--
Teva Pharmaceuticals Industries Ltd. (NYSE:TEVA) today announced the
publication of data that demonstrates significant differences in
biological and immunological effects between COPAXONE®
(glatiramer acetate, GA) and a purported generic glatiramer acetate
(GA), marketed in India, (Glatiramer®, Natco Pharma, Ltd.,
Hyderabad, India), with potential clinical ramifications.
The data, published in the online scientific journal PLOS
ONE, are the results of gene expression analysis from mouse
splenocytes (white blood cells found in the spleen) exposed to either
COPAXONE® or the purported generic GA. The study demonstrated
a predictable and therapeutically-aligned impact of COPAXONE®
on genes associated with key immune response-related cells. This is in
contrast to a significantly different and irregular impact on genes
associated with these cells by the purported generic GA.
The cells identified in this study included regulatory T cells (Tregs),
which control immune and auto-immune responses, and myeloid lineage
cells - the precursors of many immune response cells. The gene
expression impact and variability of the purported generic GA indicates
different biological effects of these drugs.
"The data from this paper shows the possible significant ramifications
of changes in physiochemical properties between COPAXONE® and
a purported generic GA.” Said Dr. Michael Hayden, President of Global
R&D and Chief Scientific Officer for Teva Pharmaceutical Industries Ltd,
and one of the study authors. “This study suggests a distinct potential
difference in the impact of a purported generic GA on the immune system
of patients, with possible implications on efficacy and safety in RRMS
patients. Teva believes the only way to truly understand the impact of
these differences is by conducting a full battery of clinical studies."
The analysis found that COPAXONE® increases levels of FOXP3
more consistently and effectively than the purported generic GA. FOXP3
is a key factor controlling the development and function of Tregs, which
may help suppress harmful autoimmunity in MS patients. Additional genes
associated with these beneficial Tregs were also increased to a greater
extent by COPAXONE® relative to the purported generic GA. The
extent to which this differential impact on Tregs might affect patient
response remains unknown.
The purported generic GA was also found to increase the expression of
genes associated with myeloid lineage cells, such as monocytes and
macrophages, to a greater extent than COPAXONE®. These cells
play an important role in the immune systems of healthy people, but can
also contribute to the worsening of RRMS. Without clinical trials, the
extent to which the increased impact of the purported generic GA on
myeloid lineage cells might alter clinical outcomes in RRMS patients
remains unknown.
The study also shows that COPAXONE® has a more consistent
biological impact across batches than the purported generic GA. A high
degree of consistency was found across 34 samples from 30 different
COPAXONE® batches. This compares with a high level of
inconsistency across only 11 samples representing just 5 different
batches of the purported generic GA.
“This extensive analysis indicates, in my view, a concerning lack of
consistency and predictability in the purported generic GA's effect on
key elements of the murine immune system. Furthermore, variability seen
in the expression of certain genes, from one batch of the purported
generic GA to another, raises the possibility that patients may not
receive the same treatment effect with each dose,” said Dr. Ben Zeskind,
CEO, Immuneering Corporation, and co-author of the study.
The full data analysis can be found by visiting PLOS
ONE. Teva employees are among the authors of the published
article; the research was commissioned and funded by Teva.
ABOUT THE STUDY
The study, co-authored by investigators from both Teva and Cambridge,
MA-based Immuneering Corporation, used transcriptional profiles to
compare a branded medicine to a purported generic version of the same
medicine, robustly characterizing differences in biological impact.
Multiple analytical methods were combined to determine whether
differentially expressed genes result from random variation, or point to
consistent differences in biological impact of the purported generic GA
compared to the branded medicine. These methods were applied to analyze
gene expression data from mouse splenocytes exposed to either COPAXONE®
or the purported generic GA. The full study manuscript can be accessed
here:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0083757
ABOUT COPAXONE®
According to the National Multiple Sclerosis Society (NMSS), multiple
sclerosis impacts 2.3 million people worldwide.
COPAXONE® (glatiramer acetate injection) is indicated for the
reduction of the frequency of relapses in relapsing-remitting multiple
sclerosis, the most common form of MS, including patients who have
experienced a first clinical episode and have MRI features consistent
with multiple sclerosis. The most common side effects of COPAXONE® are
redness, pain, swelling, itching, or a lump at the site of injection,
flushing, rash, shortness of breath, and chest pain. See additional
important information at http://copaxone.com/pdfs/PrescribingInformation.aspx.
For hardcopy releases, please see enclosed full prescribing information.
COPAXONE® is now approved in more than 50 countries
worldwide, including the United States, Russia, Canada, Mexico,
Australia, Israel, and all European countries.
Important Safety Information about COPAXONE®
Patients allergic to glatiramer acetate or mannitol should not take
COPAXONE®. Some patients report a short-term reaction right
after injecting COPAXONE®. This reaction can involve flushing
(feeling of warmth and/or redness), chest tightness or pain with heart
palpitations, anxiety, and trouble breathing. These symptoms generally
appear within minutes of an injection, last about 15 minutes, and go
away by themselves without further problems. During the postmarketing
period, there have been reports of patients with similar symptoms who
received emergency medical care. If symptoms become severe, patients
should call the emergency phone number in their area. Patients
should call their doctor right away if they develop hives, skin rash
with irritation, dizziness, sweating, chest pain, trouble breathing, or
severe pain at the injection site. If any of the above occurs, patients
should not give themselves any more injections until their doctor tells
them to begin again. Chest pain may occur either as part of the
immediate postinjection reaction or on its own. This pain should only
last a few minutes. Patients may experience more than one such episode,
usually beginning at least one month after starting treatment. Patients
should tell their doctor if they experience chest pain that lasts for a
long time or feels very intense. A permanent indentation under the skin
(lipoatrophy or, rarely, necrosis) at the injection site may occur, due
to local destruction of fat tissue. Patients should follow proper
injection technique and inform their doctor of any skin changes. The
most common side effects of COPAXONE® are redness, pain,
swelling, itching, or a lump at the site of injection, flushing, rash,
shortness of breath, and chest pain. These are not all of the possible
side effects of COPAXONE®. For a complete list, patients
should ask their doctor or pharmacist. Patients should tell their doctor
about any side effects they have while taking COPAXONE®.
Patients are encouraged to report negative side effects of prescription
drugs to the FDA. Visit www.fda.gov/medwatch
or call 1-800-FDA-1088.
ABOUT TEVA
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA) is a leading global
pharmaceutical company, committed to increasing access to high-quality
healthcare by developing, producing and marketing affordable generic
drugs as well as innovative and specialty pharmaceuticals and active
pharmaceutical ingredients. Headquartered in Israel, Teva is the world's
leading generic drug maker, with a global product portfolio of more than
1,000 molecules and a direct presence in about 60 countries. Teva's
branded businesses focus on CNS, oncology, pain, respiratory and women's
health therapeutic areas as well as biologics. Teva currently employs
approximately 46,000 people around the world and reached $20.3 billion
in net revenues in 2012.
Teva's Safe Harbor Statement under the U. S. Private Securities
Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the
current beliefs and expectations of management. Such statements are
based on management’s current beliefs and expectations and involve a
number of known and unknown risks and uncertainties that could cause our
future results, performance or achievements to differ significantly from
the results, performance or achievements expressed or implied by such
forward-looking statements. Important factors that could cause or
contribute to such differences include risks relating to: our ability to
develop and commercialize additional pharmaceutical products,
competition for our innovative products, especially Copaxone® (including
competition from innovative orally-administered alternatives, as well as
from potential purported generic equivalents), competition for our
generic products (including from other pharmaceutical companies and as a
result of increased governmental pricing pressures), competition for our
specialty pharmaceutical businesses, our ability to achieve expected
results through our innovative R&D efforts, the effectiveness of our
patents and other protections for innovative products, decreasing
opportunities to obtain U.S. market exclusivity for significant new
generic products, our ability to identify, consummate and successfully
integrate acquisitions, the effects of increased leverage as a result of
recent acquisitions, the extent to which any manufacturing or quality
control problems damage our reputation for high quality production and
require costly remediation, our potential exposure to product liability
claims to the extent not covered by insurance, increased government
scrutiny in both the U.S. and Europe of our agreements with brand
companies, potential liability for sales of generic products prior to a
final resolution of outstanding patent litigation, our exposure to
currency fluctuations and restrictions as well as credit risks, the
effects of reforms in healthcare regulation and pharmaceutical pricing
and reimbursement, any failures to comply with complex Medicare and
Medicaid reporting and payment obligations, governmental investigations
into sales and marketing practices (particularly for our specialty
pharmaceutical products), uncertainties surrounding the legislative and
regulatory pathways for the registration and approval of
biotechnology-based products, adverse effects of political or economical
instability, corruption, major hostilities or acts of terrorism on our
significant worldwide operations, interruptions in our supply chain or
problems with our information technology systems that adversely affect
our complex manufacturing processes, any failure to retain key personnel
or to attract additional executive and managerial talent, the impact of
continuing consolidation of our distributors and customers, variations
in patent laws that may adversely affect our ability to manufacture our
products in the most efficient manner, potentially significant
impairments of intangible assets and goodwill, potential increases in
tax liabilities, the termination or expiration of governmental programs
or tax benefits, environmental risks and other factors that are
discussed in our Annual Report on Form 20-F for the year ended December
31, 2012 and in our other filings with the U.S. Securities and Exchange
Commission. Forward-looking statements speak only as of the date on
which they are made and the Company undertakes no obligation to update
or revise any forward-looking statement, whether as a result of new
information, future events or otherwise.
Source: Teva Pharmaceuticals Industries Ltd.
Teva Pharmaceuticals Industries Ltd.
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