-
TEV-48125 is the first investigational treatment to meet all
efficacy endpoints in trials of both chronic and episodic migraine and
across multiple doses
-
A single administration of all tested doses of TEV-48125, in both
episodic and chronic migraine studies, resulted in a statistically
significant separation from placebo
-
53% and 59% of the patients given low and high active doses,
experienced a decrease of at least 50% in episodic migraine days
following three months of treatment. In the subgroup of patients on no
other preventive medications, a 50% reduction in episodic migraine
days was achieved in 66% and 67% of patients on active drug.
-
TEV-48125 is the first chronic migraine preventive medication
demonstrating significant improvement within days of initiation of
therapy.
-
TEV-48125 has a placebo-like safety profile with no
treatment-emergent Anti-Drug Antibodies (ADA) response observed.
JERUSALEM--(BUSINESS WIRE)--Jun. 18, 2015--
Teva Pharmaceutical Industries Ltd. (NYSE and TASE:TEVA) today announced
new data from additional analyses of its phase 2b studies in migraine
prevention on efficacy and speed of onset of two distinct doses of
TEV-48125, a novel monoclonal anti-CGRP antibody administered
subcutaneously once monthly for the preventive treatment of high
frequency episodic migraine (characterized by 8-14 days of headache per
month) and chronic migraine (headaches on at least 15 days per month).
The data is to be presented at the 57th Annual Scientific Meeting of the
American Headache Society (AHS), June 18-21, 2015, Washington DC. The
episodic migraine efficacy and onset data will be the subject of an oral
platform presentation on Saturday, June 20th, 2015, at 12:00pm ET. The
speed of onset data from the chronic migraine study will be presented at
a late breaking news poster session on Friday 19th June.
Episodic Migraine Data:
A total of 297 individuals, with a an average of 11.4 monthly migraine
days and an average of 12.5 headache days were randomized to receive
placebo or TEV-48125 (225 mg or 675 mg) given monthly. Patients were
permitted to continue using other preventive migraine medications if in
stable doses. Both doses of TEV-48125 were superior to placebo and met
the primary endpoint defined as decrease in monthly migraine days at
month 3 relative to baseline (placebo = -3.46, 225mg = -6.27, p < 0.0001
and 675 mg = -6.09, p < 0.0001) as well as the secondary endpoint,
defined as decrease monthly headache days relative to baseline (225 mg,
p < 0.001 and 675 mg, p < 0.001).
Results demonstrated that a single administration of both tested doses
of TEV-48125 resulted in a statistically significant separation from
placebo. Furthermore, a decrease of at least 50% of migraine days for
the duration of the study (weeks1-12) were seen in 28% of those
receiving placebo relative to 53% (p<0.001) and in 59% (p<0.001) of the
individuals given 225mg and 675mg correspondingly. These findings were
even further pronounced in the sub group of patients that had not used
other preventive medications in parallel – a decrease of at least 50% in
episodic migraine days was observed in 22% of those receiving placebo,
relative to 66% (p<0.001) and in 67% (p<0.01) of the individuals given
225mg and 675mg correspondingly.
Moreover, after three months of treatment, a decrease of at least 75% in
episodic migraine days for the duration of the study, amongst the
overall sample, was observed in 11%, 34% (p<0.01) and in 31% (p<0.001)
of the individuals given respectively placebo, 225mg and 675mg .The
subgroup analysis of individuals that had not used other preventive
medications showed such a reduction in 8%, 48% and in 36% of the people
given respectively placebo, 225mg and 675mg .
Chronic Migraine:
Also to be presented, within the late breaking news poster presentation
on Friday June 19th, are new ad hoc analysis data from the Phase IIb
chronic migraine study regarding efficacy at early time points. The aim
of this evaluation was to examine the efficacy and safety of TEV-48125
at time points during the first month of therapy in people with chronic
migraine, characterized by headaches on at least 15 days per month.
Results demonstrated significant decreases in the average number of
headache hours, relative to placebo, after only one week of therapy for
both TEV-48125 doses, a benefit that extended through the second and
third weeks of therapy. The 900mg dose separated from placebo after 3
days of therapy (p<0.05) and the 675/225mg dose separated on day 7
(p<0.01).
In both studies no treatment-related serious adverse events were
reported with use of TEV-48125. No other relevant differences in the
rate of treatment-emergent adverse events occurred for those receiving
TEV-48125 doses relative to placebo. Anti-drug antibodies were the
lowest in class up to this point (1.1% for TEV-48125 in this trial, and
present before drug exposure).
"The collective data generated from these studies herald promise for
millions of people who suffer from episodic and chronic migraines, a
disease with substantial implications and unmet needs," stated Marcelo
E. Bigal, Teva’s Head of Global Clinical Development for Migraine and
Headaches. "The very fast onset of preventive response, seen after a
single dose of therapy, along with the impressive decrease in migraine
days, amongst such highly refractory patients, may bring us a step
closer to provide widespread relief to people who suffer from chronic
and episodic migraine."
"The promising findings attained, for the first time in both chronic and
episodic migraine and in multiple assessed doses, enhance a growing body
of evidence that support advancing the development of TEV-48125 to Phase
III," said Michael Hayden, Teva’s President of Global R&D and Chief
Scientific Officer. "Furthermore, these results were achieved in the
presence of patients being allowed to remain on existing migraine
prevention therapy, an attribute not seen in other reported anti-CGRP
studies. We look forward to building on the progress we have made thus
far."
About the High Frequency Episodic Migraine Study (ClinicalTrials.gov
Identifier: NCT02025556)
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. The 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 the Chronic Migraine Study (ClinicalTrials.gov
Identifier: NCT02021773)
The study was a multicenter, randomized, double-blind, double-dummy,
placebo-controlled, parallel group, multi-dose study comparing TEV-48125
with placebo. Following a 28 day run-in period, qualifying patients
(n=264) were randomized to one of three treatment arms receiving high
dose TEV-48125 (900mg), low dose TEV-48125 (675/225 mg) or placebo,
given subcutaneously once a month for three months.
The study was conducted amongst 264 highly severe chronic migraine
patients who suffered from a mean of approximately 162 headache hours
per month (approx. 17 migraine days per month, and around 21 days of
headache per month). They had suffered from migraines for mean period of
18 years.
Both assessed doses of TEV-48125 were significantly superior to placebo
in reducing, relative to baseline, the number of hours with headache
(primary endpoint - p < 0.05 and p < 0.01). TEV-48125 also significantly
decreased the number of headache days of moderate or severe intensity in
month 3 (secondary endpoint - p < 0.05 and p < 0.05).
Subjects had their headache and health information captured daily during
the entire study, using an electronic headache diary system. 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, thus allowing for some CGRP
signaling during therapy. This avoids the potential effects of a
long-term total disruption to the normal physiological functions of the
CGRP system, which are unknown.
TEV-48125, administered as a once-monthly subcutaneous injection, is
being developed for both chronic migraine and high frequency episodic
migraine. Data from a recently announced Phase IIb study for the
prevention of high frequency episodic migraine, also demonstrated the
efficacy and safety of two doses of TEV-48125 in 300 patients. Findings
were consistent with the chronic migraine data achieving highly
significant reductions in mean monthly migraine days after a single
dose, establishing TEV-48125 as the first, and only, treatment to date
to meet efficacy and safety endpoints in trials of both chronic and
episodic migraine and across multiple doses.
TEV-48125 successfully completed six Phase I trials with 118 healthy
volunteers receiving active drug. 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. Most treatment-related adverse events
were mild, transient and resolved spontaneously.
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
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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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Source: Teva Pharmaceutical Industries Ltd.
Teva Pharmaceutical Industries Ltd.
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