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|May 14, 2015 8:31 a.m.|
|Teva Presents Further Data from Phase IIb with TEV-48125 in Chronic Migraine at the International Headache Society Congress (IHC): Efficacy and Safety Results at All Doses and Endpoints Present Robust Case for Progression to Phase III|
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
"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",
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
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
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.
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.
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.