Positive results from a Phase IIb study evaluating the efficacy, safety and tolerability of two doses of subcutaneous TEV-48125, an investigational anti-calcitonin gene-related peptide ( CGRP ) monoclonal antibody for the prevention of chronic migraine ( migraine with headaches on at least 15 days per month ) were presented.

The study compared two active arms of different doses of TEV-48125, administered as a subcutaneous injection, once a month for three months, against placebo.
Results demonstrated that both tested doses of TEV-48125 achieved the primary and secondary efficacy endpoints of the study at one and three months.
The data revealed a significant and clinically relevant reduction in both the number of monthly cumulative headache hours, and the number of headache days of at least moderate severity, relative to baseline.

In this study no important safety or tolerability concerns were identified. The adverse event profile for TEV-48125 appeared similar to placebo and supportive of previous phase I 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 adverse events were seen.
The study was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group, multi-dose trial comparing TEV-48125 with placebo.
Following a 28 day run-in period, qualifying patients were randomized to one of three treatment arms receiving high dose TEV-48125, low dose TEV-48125 or placebo, given subcutaneously once a month for three months.
261 patients were included in the trial, 172 receiving TEV-48125.
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.

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 is being developed for two distinct migraine indications; chronic migraine and high frequency episodic 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.
The World Health Organization ( WHO ), listed chronic migraine as 4th in a table of disabling conditions.
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. ( Xagena )

Source: Teva, 2015

XagenaMedicine2015