-
Both doses of TEV-48125 demonstrated statistically significant
reduction in the number of headache hours (primary endpoint) after
just one week
-
More than half of the patients in each dose group experienced a 50%
or more decrease in headache frequency (P<0.01 for both doses vs.
placebo)
-
Nearly one third of patients in each dose group had a 75% decrease
in headache frequency (p < 0.05 for both doses).
-
Around 15% were totally free of headaches at month three
-
By the end of the study, nearly 60% of patients reverted from
chronic (>15 headache days per month) to episodic migraine
JERUSALEM--(BUSINESS WIRE)--May 14, 2015--
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) announced the
presentation of further data from its chronic migraine phase 2b study
evaluating the efficacy and safety, versus placebo, of two doses of
TEV-48125, an anti-calcitonin gene-related peptide (CGRP) ligand
monoclonal antibody. These data will be presented on Friday, May 15th,
2015, as a late breaking oral presentation at the 17th Congress of the
International Headache Society (IHC 2015).
Both assessed doses of TEV-48125 (loading of 675 followed by monthly
injections of 225 mg or 900 mg), 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).
A priori analyses indicated that separation from placebo was seen after
a single dose of therapy, and exploratory analyses also showed both
doses of TEV-48125 separating from placebo as early as one week
post-treatment: decrease of headache hours from baseline (primary
endpoint) at week 1 was -9.1 for TEV-48125 675/225mg (p = 0.03), -11.4
for 900 mg (p = 0.003), and -2.8 for placebo. This benefit increased
progressively at 1 month, with decreases of -44.1 hours for 675/225 mg
(p = 0.003), -56.82 hours for 900 mg (p < 0.001) and -18.1 hours for
placebo. At three months decreases were -59.8 for 675/225 mg (p = 0.04)
-67.5 for 900 mg (p = 0.006) and -37.1 for placebo. Similar decreases
were seen for number of moderate/severe headache days (secondary
endpoint), where both doses separated from placebo at 2 weeks, and
maintained at 1 month and 3 months.
Additionally, TEV-48125 was associated with a significant decrease in
the consumption of acute migraine medications. No treatment-related
serious adverse events were reported with use of TEV-48125. Most common
AEs were mild injection-site pain or pruritus. No other relevant
differences in the rate of treatment-emergent adverse events occurred
for those receiving TEV-48125 doses relative to placebo. Antibodies
anti-drug were the lowest in class up to this point (1.1% for TEV-48125
in this trial, and present before drug exposure).
Furthermore, over half of the patients in both dose groups experienced a
50% or more decrease in headache frequency (p<0.01 for both doses vs.
placebo), nearly one third of patients in both dose groups had a 75%
decrease in headache frequency (p < 0.05 for both doses) and around 15%
were totally free of headaches at month three.
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. Amongst the most affected of these patients (upper third), 42%
reverted to episodic migraine in the 675/225 mg arm and 43% in the 900
mg arm, vs 22% in placebo. Overall, by the end of the study nearly 60%
of patients reverted from chronic to episodic migraine.
"Chronic migraine represents an incredibly debilitating neurological
disorder which significantly diminishes quality of life and disables the
sufferers," said Alan M. Rapoport, M.D. President of the International
Headache Society, as well as Clinical Professor of Neurology at The
David Geffen School of Medicine at UCLA, Los Angeles, and a co-author of
the study. "Although all individuals with chronic migraine qualify for
preventive therapy, most do not receive it and a substantial proportion
of those who receive it, end up discontinuing therapy. These data
provide a basis for real hope for chronic migraine patients. The speed
and magnitude of reductions in migraine hours and days seen in this
trial may significantly, and positively, impact the lives of these
patients."
"These results with TEV-48125 have not previously been achieved at any
phase in chronic migraine. They are highly statistically significant,
and provide a solid foundation to advancing the program into phase III",
said Michael Hayden, Teva’s President of Global R&D and Chief Scientific
Officer. "Patients who have suffered from chronic migraine for many
years now have a very good reason for hope."
About the Study
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.
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, 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 Chronic Migraine:
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.
The World Health Organization (WHO), listed chronic migraine as 4th
in a table of disabling conditions. This ranked it in the same
disability class as quadriplegia, acute psychosis and dementia, and more
disabling than blindness, paraplegia, angina or rheumatoid arthritis.**
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.
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.
Source: Teva Pharmaceutical Industries Ltd.
Teva Pharmaceutical Industries Ltd.
IR:
Kevin C. Mannix,
(215) 591-8912
United States
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Ran Meir, (215)
591-3033
United States
or
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926-7656
Israel
or
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Denise Bradley, (215)
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