Fremanezumab Effective in Migraine Patients With Inadequate Response to Other Treatments
Fremanezumab is the second FDA-approved preventive migraine treatment that blocks the activity of calcitonin gene-related peptide.
Fremanezumab (Ajovy; Teva Pharmaceuticals) was found to be an effective treatment for patients with chronic migraine (CM) who showed an inadequate response to other common medications for the condition, such as onaboutlinumtoxinA combined with either topiramate or valproic acid.
Fremanezumab is the second FDA-approved preventive migraine treatment in a new class of drugs that work by blocking the activity of calcitonin gene-related peptide, a molecule that is involved in migraine attacks. The first in this class, erenumab-aooe, (Aimovig) was approved in 2018.
Data from a post hoc analysis of the phase 3 FOCUS study (NCT03308968), published in Headache: The Journal of Head and Face Pain, showed comparable results to the overall study population. An interaction analysis of treatment-by-subgroup found no significant differences in efficacy between 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," the study authors wrote.
The 12-week, double-blind FOCUS study had an additional 12-week open-label treatment period that enrolled adults (n = 838) with diagnosed CM or episodic migraine who showed an 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.
In a quarterly subgroup analysis of the fremanezumab cohort, monthly fremanezumab cohort, and placebo cohort, 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.
During the 12-week treatment period, changes from baseline monthly migraine days (MMDs) were significantly more for fremanezumab-treated patients (quarterly: –3.8 [P = .003]; monthly: –3.4 [P = .012]) compared with placebo (–0.9). The decrease was apparent at months 1 and 3 in both fremanezumab dosing regimens and at month 2 with quarterly fremanezumab.
Further, a decrease of at least 30% in MMDs from baseline were significantly greater in the fremanezumab groups (quarterly: 44% [P = .002]; monthly: 37% [P = .017]) compared with placebo (13%) over the 12-week treatment period. The same held true for proportions of patients who achieved a 50% decrease from baseline in the quarterly fremanezumab group (25% vs placebo: 5%; P = .024).
Through 3 months of posttreatment, the proportions of patients who had a greater than or equal to 30% decrease in MMDs were significantly greater than those on placebo. The proportion of patients with at least a 50% decrease was significantly greater with quarterly fremanezumab versus 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," the study authors wrote.
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