Teva’s Phase 2B Migraine Program

Teva Pharmaceutical Industries Ltd., has announced that Lancet Neurology published online, as back-to-back articles, the results from two Phase 2b studies of TEV-48125, a monoclonal anti-calcitonin gene-related peptide (CGRP) antibody investigational treatment for the prevention of chronic migraine and high frequency episodic migraine (HFEM).

Teva says that the Phase 2b clinical development program consistently met all primary and secondary efficacy and safety endpoints for TEV-48125 in 564 patients and across multiple doses. Clinical improvements were exhibited after a single administration of all tested doses of TEV-48125 in both episodic and chronic migraine studies.

These results were achieved in the presence of patients being allowed to remain on existing migraine prevention therapy and the results demonstrated significant separation in favor of TEV-48125 even in patients considered to be failing current optimal therapy.

“These findings constitute an exciting landmark in the development of migraine prevention treatment options,” said Marcelo E. Bigal, MD., PhD., Senior Vice President of Clinical Operations & Innovation and Headaches Therapeutic Area Lead at Teva. “We are delighted with the publication in Lancet Neurology, a journal that recognizes the rigor of these studies; we foresee the potential of this drug in treating a very prominent unmet medical need.”

“It is critical to understand the importance of the data published in these two studies. The positive impact of this novel treatment approach should dramatically improve the lives of migraineurs”, said Alan M. Rapoport, MD., Immediate Past-President of the International Headache Society, Clinical Professor of Neurology at The David Geffen School of Medicine at UCLA, Los Angeles, and a co-author of both studies.

“Patients with chronic or frequent episodic migraine are often in extreme pain and severely disabled, sometimes unable to leave home for 2-3 days at a time. I hope that treating physicians will digest these studies with the same level of excitement and hope that I have. In my opinion, we are on a path to dramatic and unprecedented progress in the management of this incapacitating condition.”

Teva Explaines the Chronic Migraine Study

Both assessed doses of TEV-48125 (loading of 675mg followed by monthly injections of 225mg or 900mg), were significantly superior to placebo in reducing, relative to baseline, the number of headache-hours (primary endpoint: p = 0.038 and p = 0.0057) and the number of headache days of moderate or severe intensity in month 3 (secondary endpoint: p < 0.0345 and p =0.0237). Consistent clinical improvements were evident as early as one month after treatment initiation, demonstrating a rapid onset of relief. Post-hoc analysis indicated that 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.
Treatment with TEV-48125 was also associated with statistically significant decreases in acute drug consumption in parallel. These results were achieved amongst highly severe chronic migraine patients (suffered from migraines for a mean period of 18 years, with approximately 17 migraine days per month), who were allowed to remain on other migraine prevention therapies.
Teva Explaines the High Frequency Episodic Migraine (HFEM) 

This is the first study to report on more than one dose of a monoclonal anti-CGRP antibody for the preventive treatment of HFEM, and the study was highly positive, especially considering the severity of the disorder. Participants had migraine for nearly two decades, with a mean of 11.4 migraine-days per month, and 12.5 headache-days per month.
Following 12 weeks, both doses of TEV-48125 (225 mg and 675 mg) exceeded primary and secondary endpoints, achieving statistically significant and clinically meaningful reductions in mean monthly migraine days and monthly headache days as well as significantly diminished number of days and hours of headaches of at least moderate severity.
A decrease of at least 50% of migraine days for the duration of the study were seen in 53% (p = 0.0005) and 59% (p<0.0001) of the individuals given 225mg and 675mg correspondingly versus 28% of those receiving placebo. A decrease of at least 75% in episodic migraine days was observed in 11%, 34% (p = 0.0001) and in 31% (p = 0.0008) of the individuals given placebo, 225mg and 675mg respectively. Design and analyses also had the same rigor of a phase 3 trial.
In both studies no treatment-related serious adverse events were reported with use of TEV-48125. No relevant differences in the rate of treatment-emergent adverse events occurred for those receiving TEV-48125 doses relative to placebo. Anti-drug antibodies (1% for TEV-48125, and present before drug exposure) detected an optimized assay of regulatory quality and much lower than detected with other monoclonal anti-CGRP antibodies.