Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) (“Teva”) announced
today the successful completion of its Phase IIb migraine prevention
program with positive top-line results from a Phase IIb study evaluating
the efficacy, safety and tolerability of two doses of subcutaneous
TEV-48125 for the prevention of high frequency episodic migraine
(characterized by 8-14 days of headache per month).
TEV-48125 is a novel investigational anti-calcitonin gene-related
peptide (CGRP) monoclonal antibody, and these data, together with the
recent results achieved in the difficult to treat chronic migraine
setting, make this the first therapy to successfully meet efficacy
endpoints in the prevention of both chronic and episodic migraine, and
at multiple doses, in advanced clinical trials.
Initial analysis of results demonstrated that both doses of TEV-48125
met primary and secondary endpoints achieving significant reductions in
mean monthly migraine days and monthly headache days relative to
baseline. These are considered as validated endpoints to assess benefits
of new migraine treatments.
Additionally, a single administration of both tested doses of TEV-48125
resulted in a statistically significant separation from placebo. Data
confirm that treatment with TEV-48125 resulted in separation for both
primary and secondary endpoints, at all months of therapy, in both the
chronic and episodic migraine clinical trials.
Furthermore, these results were achieved in the presence of patients
being allowed to remain on existing migraine prevention therapy, and
without limitation on the amount of acute migraine treatment used. This
was an attribute of the TEV-48125 phase IIb studies not seen in other
reported anti-CGRP studies, and the results demonstrated separation in
favor of TEV-48125 even in patients considered to be on optimal current
therapy. Overall, four different doses across two indications studied in
a total of 561 patients met all study endpoints establishing clinical
proof of concept for anti-CGRP ligand therapy.
“The collective data from this phase II program have validated the
concept of targeting the anti-CGRP ligand with TEV-48125 with a level of
confidence that we did not foresee. We now have reason to believe that
we have developed an approach that gives us the foundation, with
identified doses, to progress to a Phase III program that we hope will
take TEV-48125 a step closer to potentially making a significant
difference to patients’ lives” stated Marcelo E. Bigal, Teva’s Head of
Global Clinical Development for Migraine and Headaches.
The study compared two active arms of high and low dose TEV-48125,
administered as a subcutaneous injection, once a month for three months,
against placebo. In this study no important safety or tolerability
concerns were identified. The adverse event profile for TEV-48125
appeared similar to placebo for most parameters and supportive of
previous Phase I and II safety data. Of the adverse events reported,
mild, transient injection site discomfort and redness was infrequent but
higher than that observed in the placebo group. No serious
treatment-related serious adverse events were seen.
"Migraine is a truly debilitating disorder. Up to 15% of the global
population is affected by migraine. It causes highly disabling pain and
other symptoms that disrupt the life of the patient and their families,"
said Michael Hayden, Teva’s President of Global R&D and Chief Scientific
Officer. "Our phase II results are striking in their clarity. They
provide a quality of insight rarely seen at this stage of development
and offer the prospect of a new chapter in the lives of patients who
have been suffering the blight of recurrent migraine for many years. "
Full results from the study will be presented at a forthcoming
scientific meeting and will be submitted to a peer-reviewed journal for
publication.
About the HFEM Study
The study was a multicenter, randomized, double-blind,
placebo-controlled, parallel-group, study comparing the efficacy and
safety of two doses of subcutaneous TEV -48125 with placebo for the
preventive treatment of high frequency episodic migraine in 297 patients.
Multiple doses were selected for testing to define dose-response and
allow selection of doses for a Phase 3 study.
Treatment was administered once every 28 days (i.e.; once monthly) over
a 3-month period. 300 patients were enrolled and randomized to one of
three treatment arms receiving high dose TEV-48125, low dose TEV-48125
or placebo, administered subcutaneously once a month. The study was
conducted in approximately 60 centers in the USA.
About TEV-48125
TEV -48125 (formerly LBR-101/ RN-307) is a monoclonal antibody that
binds to calcitonin gene-related peptide (CGRP), a well-validated target
in migraine. CGRP signaling may be disrupted by targeting the ligand
itself or its receptor.
Teva's approach targets the ligand, allowing for some CGRP signaling
during therapy, which may avoid the potential, unknown, effects of a
long-term total disruption to the normal physiological functions of the
CGRP system. TEV-48125 is being developed for two distinct migraine
indications; chronic migraine and high frequency episodic migraine.
Positive results from the Phase IIb chronic migraine study were
announced in February 2015, demonstrating a significant reduction in
both the number of monthly cumulative headache hours, and the number of
headache days of at least moderate severity, relative to baseline, and
for the first time validating the target in chronic migraine.
TEV-48125 successfully completed five Phase I trials with 94 healthy
volunteers. Results were published
in Cephalalgia, the official journal of the International
Headache Society, in December 2013, and presented at the 2014 annual
meeting of the American Academy of Neurology.
About Migraine
Global prevalence of migraine is estimated to be almost 15%. Migraine
was ranked seventh highest among specific causes of disability globally,
responsible for 2.9% of all Years Lost to Disability (YLDs). Migraine
is, by a wide margin, the leading cause of disability among neurological
disorders, accounting for over half of all YLDs attributed to these (J
Headache Pain. 2013; 14(1): (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606966/).
In the United Kingdom, for example, some 25 million working- or
school-days are lost every year because of migraine alone (http://www.who.int/mediacentre/factsheets/fs277/en/).
Approximately 3.2 million Americans, mostly women, suffer from Chronic
Migraine. Chronic migraine is characterized by headaches on at least 15
days per month. Chronic migraine patients are often referred to as the
‘invisible population’ due to the isolating nature of the condition,
where patients are left, in many cases, effectively house-bound.
Chronic migraine imposes a considerable burden on patients, magnified by
the paucity of approved treatment options for this condition. More than
one in four of all migraineurs are candidates for preventive therapy,
and a substantial proportion of those who might benefit from prevention
do not receive it. Consequently, the prophylactic treatment of chronic
migraine continues to present considerable challenges, and there remains
a significant medical need for new, safe and effective migraine
prophylaxis options.
Episodic Migraine impacts up to 14% of the population, and approximately
20% of women, globally. High frequency episodic migraine substantially
impacts the individual, their family, and society. Episodic migraine is
the most common neurological condition, more prevalent than diabetes,
epilepsy and asthma combined.
About Teva
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a leading
global pharmaceutical company that delivers high-quality,
patient-centric healthcare solutions to millions of patients every day.
Headquartered in Israel, Teva is the world’s largest generic medicines
producer, leveraging its portfolio of more than 1,000 molecules to
produce a wide range of generic products in nearly every therapeutic
area. In specialty medicines, Teva has a world-leading position in
innovative treatments for disorders of the central nervous system,
including pain, as well as a strong portfolio of respiratory products.
Teva integrates its generics and specialty capabilities in its global
research and development division to create new ways of addressing unmet
patient needs by combining drug development capabilities with devices,
services and technologies. Teva's net revenues in 2014 amounted to $20.3
billion. For more information, visit www.tevapharm.com.
Teva's Safe Harbor Statement under the U. S. Private Securities
Litigation Reform Act of 1995:
This release contains forward-looking statements, which 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 orally-administered alternatives, as well as
from potential purported generic equivalents) and our ability to
migrate users to our 40 mg/mL version; the possibility of material
fines, penalties and other sanctions and other adverse consequences
arising out of our ongoing FCPA investigations and related matters; our
ability to achieve expected results from the research and development
efforts invested in our pipeline of specialty and other products; our
ability to reduce operating expenses to the extent and during the
timeframe intended by our cost reduction program; our ability to
identify and successfully bid for suitable acquisition targets or
licensing opportunities, or to consummate and integrate acquisitions;
the extent to which any manufacturing or quality control problems damage
our reputation for quality production and require costly remediation;
increased government scrutiny in both the U.S. and Europe of our patent
settlement agreements; our exposure to currency fluctuations and
restrictions as well as credit risks; the effectiveness of our patents,
confidentiality agreements and other measures to protect the
intellectual property rights of our specialty medicines; the effects of
reforms in healthcare regulation and pharmaceutical pricing,
reimbursement and coverage; governmental investigations into sales and
marketing practices, particularly for our specialty pharmaceutical
products; adverse effects of political or economic instability, major
hostilities or acts of terrorism on our significant worldwide
operations; interruptions in our supply chain or problems with internal
or third-party information technology systems that adversely affect our
complex manufacturing processes; significant disruptions of our
information technology systems or breaches of our data security;
competition for our generic products, both from other pharmaceutical
companies and as a result of increased governmental pricing pressures;
competition for our specialty pharmaceutical businesses from companies
with greater resources and capabilities; the impact of continuing
consolidation of our distributors and customers; decreased opportunities
to obtain U.S. market exclusivity for significant new generic products;
potential liability in the U.S., Europe and other markets for sales of
generic products prior to a final resolution of outstanding patent
litigation; our potential exposure to product liability claims that are
not covered by insurance; any failure to recruit or retain key
personnel, or to attract additional executive and managerial talent; any
failures to comply with complex Medicare and Medicaid reporting and
payment obligations; significant impairment charges relating to
intangible assets, goodwill and property, plant and equipment; the
effects of increased leverage and our resulting reliance on access to
the capital markets; potentially significant increases in tax
liabilities; 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; variations in patent laws that may
adversely affect our ability to manufacture our products in the most
efficient manner; environmental risks; and other factors that are
discussed in our Annual Report on Form 20-F for the year ended December
31, 2014 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 we assume no obligation to update or revise any
forward-looking statement, whether as a result of new information,
future events or otherwise.
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