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|June 18, 2015 8:30 a.m.|
|Teva to Present New Findings at the American Headache Society (AHS) Meeting – Analysis of Migraine Phase IIb Studies Provides Novel Insights into TEV-48125 Efficacy and Safety in Both Episodic & Chronic Migraine|
The data is to be presented at the 57th Annual Scientific Meeting of the
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 .
Also to be presented, within the late breaking news poster presentation
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
"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
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
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
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
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/).
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.
Teva's Safe Harbor Statement under the
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
Teva Pharmaceutical Industries Ltd.