Monoclonal Antibody Efficacious for Treatment of Migraines

Phase 2 results show anti-CGRP receptor monoclonal antibody effective for the prevention of episodic migraine.

VANCOUVER, British Columbia — AMG 334, a human anti-calcitonin gene-related peptide (anti-CGRP) receptor monoclonal antibody, demonstrated sustained efficacy for the prevention of episodic migraine in a phase 2 trial presented at the 2016 annual meeting of the American Academy of Neurology (AAN).

“AMG 334 produced clinically meaningful and statistically significant reductions in the number of migraine days experienced compared to placebo,” said Robert Lenz, MD, PhD, study investigator and vice president of neuroscience development at Amgen (Thousand Oaks, California). “Importantly, the safety and tolerability of AMG 334 appeared similar to placebo.”

According to Dr Lenz, the catalyst for the study was the current unmet need concerning migraine prevention therapies. He added that up to 80% of patients on existing preventive therapies discontinue treatment after 1 year. In addition, one-third of patients qualify for preventive therapies, yet only 5% actually receive it.

“There is substantial clinical evidence supporting a causal role for CGRP in migraine, including the finding that CGRP levels increase during a migraine and that infusing CGRP into patients who suffer spontaneous migraines induces migraine-like attacks,” he said. “Therefore, we developed a human monoclonal antibody called AMG 334 that selectively inhibits the CGRP receptor to determine if this would be effective in preventing migraine in patients who suffer from frequent migraines.”

For the double blind, phase 2 study, Dr Lenz and colleagues randomly assigned 483 adults with episodic migraine to monthly subcutaneous injections of AMG 334 (7 mg, 21 mg, or 70 mg) or placebo.

The primary end point was defined as change from baseline in monthly migraine days, while secondary end points included 50% responder rate and change in monthly migraine attacks.

After completion of the 12-week, double-blind phase, patients were allowed to continue in an open-label extension, receiving AMG 334 70 mg for up to 5 years. The present interim analysis is based on available efficacy data of up to 52 weeks from the ongoing open-label extension and up to 76 weeks for the safety data.

Baseline data revealed that mean monthly migraine days were 8.7.

At 12 weeks, there were greater reductions in migraine days with AMG 334 70 mg compared with placebo (-3.40 vs -2.28; P=.021), but not with the 2 lower AMG 334 doses (P>.05). There were also higher 50% responder rates with AMG 334 70 mg than with placebo (47% vs 30%; P=.011), although there were no significant differences in change in monthly migraine attacks between groups.

In other analysis, 382 of 395 eligible patients entered the open-label extension, with a median exposure of 34.1 weeks at data cutoff.

Among this population, additional reductions from baseline in mean monthly migraine days were reported for at least 52 weeks. Specifically, from baseline, 62% of patients experienced a ≥50% reduction in migraine days, 38% experienced a ≥75% reduction, and 19% experienced a 100% reduction.

No major safety findings were reported during the double-blind phase, with tolerability being similar between AMG 334 and placebo, and no new safety signals occurred during the open-label extension.

“There is a substantial unmet need in migraine prevention … [for] effective and well-tolerated therapies,” Dr Lenz said. “AMG 334 is a novel targeted therapy that generated positive data in a large global phase 2 study. Phase 3 clinical trials in episodic and chronic migraine are underway, and we hope that AMG 334 could be a novel treatment option in patients suffering from frequent migraines.”

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Lenz R, Dodick D, Goadsby P, et al. Prevention of episodic migraine with AMG 334, a human anti-calcitonin gene-related peptide receptor monoclonal antibody: phase 2 study results and 52-week analysis of open-label extension. Presented at: The 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, British Columbia, Canada. Abstract I3.001.