Fremanezumab Shows Benefit for Migraine With Prior Inadequate Response to OnabotulinumtoxinA Paired With Topiramate or Valproic Acid

Over a 12-month treatment period, fremanezumab afforded significantly greater reductions in monthly migraine days and higher responder rates compared with placebo for patients with chronic migraine.

Fremanezumab (Ajovy; Teva Pharmaceuticals), an FDA-approved migraine preventative, might be a particularly effective option for patients with chronic migraine (CM) who had an inadequate response to commonly used treatments, specifically onaboutlinumtoxinA combined with either topiramate or valproic acid.

Newly published data from a post hoc analysis of the phase 3 FOCUS study (NCT03308968) showed results that were comparable to those of the overall study population. In a treatment-by-subgroup interaction analysis, no significant difference was shown in efficacy between those in the subgroup with prior inadequate response and the subgroup without prior inadequate response (quarterly fremanezumab: 0.32 [estimate SE, 1.13 ]; P = .775; monthly fremanezumab: 1.58 [estimate SE, 1.15]; P = .173).

"These results may be particularly relevant for countries in which health authorities require prior inadequate response to multiple preventive medications, such as onabotulinumtoxinA, before initiating fremanezumab preventive treatment for CM," senior author Joshua Cohen, MD, MPH, FAHS, senior director and global lead, migraine and headache, Teva Pharmaceuticals, and colleagues concluded.

FOCUS was a 12-week, double-blind study with an additional 12-week open-label treatment period that enrolled adults (n = 838) with diagnosed CM or episodic migraine who had inadequate response to 2 to 4 prior migraine preventive medication classes over the past 10 years. During the double-blind period, participants were randomized 1:1:1 to receive quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo.

Fremanezumab, a fully humanized monoclonal antibody that selective targets the calcitonin gene-related peptide (CGRP), was evaluated in a subgroup of 138 patients. In the quarterly fremanezumab, monthly fremanezumab, and placebo groups, 96% (50 of 52), 96% (44 of 46), and 83% (33 of 40) of participants, respectively, had prior inadequate response to topiramate and 21% (11 of 52), 35% (16 of 46), and 28% (11 of 40) had prior inadequate response to valproic acid, respectively.

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During the 12-week treatment period, changes from baseline monthly migraine days (MMDs) were significantly greater for fremanezumab-treated patients (quarterly: –3.8 [P = .003]; monthly: –3.4 [P = .012]) vs placebo (–0.9). These significant reductions were apparent at months 1 and 3 in both fremanezumab dosing regimens and at month 2 with quarterly fremanezumab.

Reductions of at least 30% in MMDs from baseline during the 12-week treatment period were also significantly higher in the fremanezumab groups (quarterly: 44% [P = .002]; monthly: 37% [P = .017]) vs placebo (13%). Similarly, this was true for proportions of patients achieving 50% reduction from baseline in the quarterly fremanezumab group (25% vs placebo: 5%; P = .024).

At months 1, 2, and 3 months posttreatment, the proportions of patients with greater than or equal to 30% reduction in MMDs were significantly higher than those on placebo. Furthermore, the proportion of patients with at least 50% reduction was significantly higher with quarterly fremanezumab compared with placebo at months 1 and 2.

"The number of participants in this subgroup was relatively small, particularly compared to the overall FOCUS population, which may have contributed to a reduced ability to detect treatment effects. Nevertheless, results were generally comparable to those observed for the overall FOCUS population," Cohen et al wrote.

In September 2018, fremanezumab became FDA-approved for the prevention of migraine in adults. The drug was originally approved as a prefilled syringe indicated for 1-time use. In January 2020, the FDA approved an autoinjector for the delivery of fremanezumab, joining Amgen’s erenumab (Aimovig) and Eli Lilly’s galcanezumab (Emgality) as the anti-CGRP agents on the market available for administration via autoinjector.2

1. Ferrari MD, Zuurbier KWM, Barash S, Ning X, Cohen JM. Fremanezumab in individuals with chronic migraine who had inadequate response to onabotulinumtoxinA and topiramate or valproic acid. Headache. Published online April 6, 2022. doi:10.1111/head.14294
2. Teva announces FDA approval of ajovy (fremanezumab-vfrm) injection autoinjector. News release. Teva Pharmaceuticals. January 28, 2020. Accessed April 15, 2022.