OBJECTIVE: To evaluate the impact of fremanezumab on the severity and duration 
of remaining migraine attacks in patients with chronic migraine (CM) or episodic 
migraine (EM).
BACKGROUND: Fremanezumab is a fully humanized monoclonal antibody (IgGΔa) that 
selectively targets calcitonin gene-related peptide and is efficacious in 
reducing migraine frequency.
METHODS: This exploratory post hoc analysis included data from three randomized, 
double-blind, 12-week, phase 3 studies (HALO CM, HALO EM, and FOCUS). In all 
three studies, patients with CM or EM were randomized 1:1:1 to receive 
subcutaneous quarterly fremanezumab (month 1/2/3: 675 mg/placebo/placebo), 
monthly fremanezumab (month 1/2/3: 675 mg [CM], 225 mg [EM]/225 mg/225 mg), or 
matched monthly placebo. Changes from baseline were evaluated in the proportion 
of headache days of at least moderate severity, peak severity of headache days, 
mean monthly headache hours (of any severity and at least moderate severity), 
and mean headache hours per headache day of any severity.
RESULTS: A total of 2843 patients were randomized with 2823 patients included in 
the efficacy analyses across all studies (HALO CM, N = 1121; HALO EM, N = 865; 
FOCUS, N = 837). At study baseline, mean (standard deviation [SD]) monthly 
number of headache days rated moderate or severe in the quarterly fremanezumab, 
monthly fremanezumab, and placebo groups, respectively, were 13.2 (5.5), 12.8 
(5.8), and 13.3 (5.8) in HALO CM; 7.2 (3.1), 6.8 (2.9), and 6.9 (3.1) in HALO 
EM; and 12.4 (5.8), 12.7 (5.8), and 12.8 (5.9) in FOCUS. Patients experienced 
significant least-squares mean (LSM; 95% confidence interval) percent reductions 
from baseline in monthly number of headache days rated moderate or severe during 
the 12 weeks: HALO CM, quarterly fremanezumab, 34.5% (-39.8, -29.2) and monthly 
fremanezumab, 36.2% (-41.4, -31.0) vs. placebo, 19.6% (-20.0, -14.3); HALO EM, 
quarterly fremanezumab, 40.7% (-47.8, -33.5) and monthly fremanezumab, 43.4% 
(-50.4, -36.3) vs. placebo, 17.9% (-24.9, -11.0); and FOCUS, quarterly 
fremanezumab, 36.5% (-41.9, -31.1) and monthly fremanezumab, 38.6% (-44.0, 
-33.3) vs. placebo, 3.5% (-8.9, 1.8); all p < 0.0001. At study baseline, mean 
(SD) number of monthly headache hours rated moderate or severe in the quarterly 
fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 66.4 
(58.8), 68.0 (53.9), and 68.5 (57.0) in HALO CM; 33.3 (25.4), 31.7 (23.7), and 
31.6 (23.2) in HALO EM; and 59.2 (54.7), 64.3 (65.2), and 65.9 (70.2) in FOCUS. 
Significant reductions were observed in LSM (standard error) number of monthly 
headache hours of at least moderate severity: HALO CM, quarterly fremanezumab, 
24.4 (2.5) and monthly fremanezumab, 26.4 (2.3) vs. placebo, 14.1 (2.5); HALO 
EM, quarterly fremanezumab, 14.5 (1.4) and monthly fremanezumab, 15.5 (1.3) vs. 
placebo, 8.1 (1.3); and FOCUS, quarterly fremanezumab, 16.8 (3.0) and monthly 
fremanezumab, 18.3 (3.0) vs. placebo, 2.3 (3.0); all p < 0.001.
CONCLUSION: These analyses demonstrated that quarterly or monthly treatment with 
fremanezumab significantly reduced headache severity and duration in patients 
with CM or EM, including in patients with documented inadequate response to two 
to four prior migraine preventive medication classes.