Calcitonin-gene related peptide antibody inhibition shows migraine prevention promise

Oct 2 2015

By Lucy Piper, Senior medwireNews Reporter

TEV-48125, a monoclonal anti-calcitonin-gene related peptide (CGRP) antibody, is well tolerated and effective in the prevention of high-frequency episodic migraine and chronic migraine, findings from two phase IIb studies show.

Lead researcher in both studies Marcelo Bigal (Teva Pharmaceuticals, Frazer, Pennsylvania, USA) and colleagues found that the drug, delivered subcutaneously, was effective in reducing the number of headache–days per month in the case of high-frequency episodic migraine and the number of headache–hours for chronic migraine.

The onset of action was quick and the drug was well tolerated with no safety concerns emerging. As a result, the teams call for the clinical development of TEV-48125 in a phase III trial for the prevention of high-frequency episodic and chronic migraines.

In the first trial, 297 men and women experiencing migraine headaches on 8 to 14 days per month were randomly assigned to receive placebo, TEV-48125 225 mg or TEV-48125 675 mg every 28 days for 12 weeks.

By 9 to 12 weeks, the reduction in migraine–days compared with baseline was significantly greater among patients taking TEV-48125 than those taking placebo, at an average of 6.27 days and 6.09 days with the 225 mg and 675 mg dose, respectively, versus 3.46 days with placebo.

Both doses significantly reduced migraine–days relative to placebo during all three treatment cycles, the researchers report, and in a post hoc analysis a significantly higher proportion of patients taking TEV-48125 had more than a 50% or 75% reduction in migraine–days relative to placebo.

The findings were similar for the number of headache–days and in both cases clinical benefits were consistently seen during the first 28 days of treatment.

Adverse events and treatment-related events were similar between TEV-48125- and placebo-treated patients, with little difference in severity and there were no meaningful haemodynamic, cardiovascular or liver function changes.

In the second trial, the efficacy of TEV-48125 was studied in 264 patients with chronic migraine, who again were treated with TEV-48125 or placebo every 28 days for 12 weeks. There were two TEV-48125 dose groups; the first received 675 mg during the first round of treatment and 225 mg in subsequent rounds, while the second received 900 mg during all three rounds.

By weeks 9 to 12, the reduction in headache–hours from baseline was 59.84 hours among patients taking TEV-48125 675/225 mg and 67.51 hours in those taking the 900 mg dose versus 37.10 hours in the placebo group.

There was also a significantly greater reduction in the number of days spent with moderate or severe headache among the patients taking either dose of TEV-48125 relative to placebo, and for both headache–hours and moderate or severe headache–days, differences relative to placebo were significant.

The researchers note in The Lancet Neurology that TEV-48125 treatment was also associated with a significant decrease in the use of acute drugs for migraine.

“These findings for the first time validate CGRP as a therapeutic target in patients with chronic migraine”, they comment.

However, the team also acknowledges that roles for central and peripheral targets other than CGRP have been identified in migraine and therefore concedes that not all individuals with migraine will respond to anti-CGRP therapies.

This was a point picked up in a related comment by Julio Pascual (University Hospital Marqués de Valdecilla, Santander, Spain), who notes that this may explain, in part, why 45% of chronic migraine patients receiving high dose TEV-48125 and 47% of patients receiving the low dose did not achieve a 50% reduction in moderate or severe headache–days.

“All available data point to CGRP antibodies as a step forward in migraine prevention, with potential advantages in tolerability and treatment adherence”, he says, adding, however, that “the characteristics of responders to these antibodies, their ideal dose, and their long-term neurological and systemic safety must be refined.”

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