Fremanezumab May Offer Prevention for Refractory Migraine

Damian McNamara

July 16, 2018

SAN FRANCISCO — The calcitonin gene-related peptide (CGRP) antagonist fremanezumab (Teva Pharmaceuticals) may offer a treatment option for chronic migraine prevention in patients in whom other preventive therapies have failed. 

Over 12 weeks, the drug significantly reduced the monthly average number of headache days of at least moderate severity, as well as the number of migraine days, in patients previously treated with topiramate or onabotulinumtoxinA (Botox, Allergan) compared with those receiving placebo.

Fremanezumab may be efficacious in these more difficult-to-treat populations, the researchers noted in a poster presented here at the American Headache Society (AHS) Annual Meeting 2018.

"Topiramate and onabotulinumtoxinA are commonly used as preventive treatment for chronic migraine, yet there remains an unmet need for preventive treatment in those who have previously tried these therapies," study investigator Joshua M. Cohen, MD, MPH, from Teva Global Medical Affairs, told Medscape Medical News.

"For those who had previously tried topiramate, effect sizes for both migraine days and headache days of at least moderate severity exceeded the effect sizes seen in the overall trial population," he added

The investigators used data from the previously reported phase 3 HALO study. The 1130 HALO participants were randomly assigned to receive subcutaneous injections of fremanezumab at a dose of 675 mg at initiation followed by monthly 225 mg for 2 months (monthly dose regimen), fremanezumab at 675 mg at initiation followed by placebo for 2 months (quarterly dose regimen), or three monthly doses of matching placebo.

HALO met its primary endpoint, showing that patients taking fremanezumab experienced a statistically significant reduction in the number of monthly headache days of at least moderate severity compared with placebo (change of –2.5 days) during the 12-week period after the first dose, for both monthly (change of –4.6 days; P < .0001) and quarterly (change of –4.3 days; P < .0001) dosing regimens.

According to the World Health Organization, migraine is the second leading cause of years lived with disability and the leading cause of disability in people age 15 to 49 years. Chronic migraine represents a particularly debilitating subset of the disease, with more significant impairment at work, at home, and in social functioning. 

Fewer Headache Days

As was seen in to the overall findings, when investigators assessed the 338 HALO participants with a history of topiramate treatment, fremanezumab decreased the number of headache days of at least moderate severity and the number of migraine days compared with placebo at 12 weeks. 

The 106 patients in this group who received the quarterly regimen of fremanezumab experienced a change of –4.4 days of headaches per month compared with –1.7 days among the 117 patients in the placebo group (P < .0001). The 115 patients treated with monthly fremanezumab experienced –4.7 days of headache (P < .0001 compared with placebo).

In terms of migraine days, the quarterly fremanezumab group experienced a change of –4.9 days compared with –2.5 in the placebo group (P = .0005). At the same time, the monthly fremanezumab recipients experienced a change of –5.1 days by 12 weeks, also statistically significant compared with placebo (P = .0001).

The HALO study included 165 people with chronic migraine previously treated with onabotulinumtoxinA. Again, fremanezumab was associated with a reduction in days of headache of at least moderate severity and migraine days compared with placebo at 12 weeks.

Among the 66 patients in this group treated with quarterly fremanezumab, researchers reported a change of –3.3 headache days compared with –2.0 days among the 49 in the placebo group. This difference was not statistically significant. The change among the 50 people receiving monthly fremanezumab was –4.1 headache days (P = .0284 vs placebo).

The investigators also compared change in migraine days. The quarterly fremanezumab group experienced a change of –4.0 migraine days compared with –2.3 in the placebo group. Again, this finding was not statistically significant. The monthly fremanezumab group experienced a change of –4.5 migraine days, a significant difference compared with placebo (P = .0346).

"Currently, a phase 3b trial is underway to evaluate fremanezumab in patients who failed multiple prior preventive therapies," Cohen said. "We hope to present additional data on efficacy in patients who failed other preventive therapies at upcoming congresses."

Useful Research

Commenting on the findings for Medscape Medical News, Andrew Hershey, MD, PhD, a pediatric neurologist at Cincinnati Children's Hospital and a professor in the Department of Neurology and Rehabilitation Medicine at the University of Cincinnati College of Medicine, Ohio, said that in real-world clinical practice, fremanezumab will likely be used for refractory patients.

This study is useful, he added, because figuring out how efficacious the CGRP antibodies are in a refractory population "is still largely an unknown."

"If you really look at all these reports [on CGRP antibodies], the difference compared to placebo really averages about two headaches a month. For those patients who do get better, it's great for them, but it's not as much as the industry tends to tout, which is what my editorial in the New England Journal of Medicine about 6 months ago summarized."

Hershey predicted that some neurologists may ultimately make an "either/or" decision to use a CGRP antibody or onabotulinumtoxinA as their second-line treatment strategy, depending on patient presentation and any comorbidities or contraindications.

Teva Pharmaceuticals funded the study. Cohen is a Teva employee. Hershey has disclosed no relevant financial relationships.

American Headache Society (AHS) Annual Meeting 2018. Abstract #PF09. Presented June 29, 2018.

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