Dataset Information

Efficacy and safety of fremanezumab for chronic migraine prevention: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in Japanese and Korean patients.

ABSTRACT:

Objective

To determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM).

Background

Available preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene-related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large-scale, international Phase 3 trials.

Methods

Randomized, placebo-controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12 weeks after the first dose.

Results

Among 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least-squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (-4.1 ± 0.4) and fremanezumab quarterly (-4.1 ± 0.4) than with placebo (-2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was -1.7 days (-2.54, -0.80) for the fremanezumab monthly group and -1.7 days (-2.55, -0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12-week period ± SE: fremanezumab monthly, -3.7 ± 0.4; fremanezumab quarterly, -3.9 ± 0.4; placebo, -2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six-item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, -8.1 ± 0.7; fremanezumab quarterly, -8.0 ± 0.7; placebo, -6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection-site reactions as placebo (patients with at least one treatment-emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%]).

Conclusion

Fremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected.

SUBMITTER: Sakai F

PROVIDER: S-EPMC8456899 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo evaluate the efficacy and safety of two dosing regimens of fremanezumab in Japanese and Korean patients with episodic migraine.BackgroundEpisodic migraine, which accounts for more than 90% of migraine cases, is inadequately addressed by widely available preventive therapies. Fremanezumab, a monoclonal antibody that selectively targets the trigeminal sensory neuropeptide calcitonin gene-related peptide involved in migraine pathogenesis, has demonstrated efficacy in international Phase 3 trials of patients with both chronic and episodic migraine.MethodsThis Phase 3 randomized, placebo-controlled trial randomly assigned patients with episodic migraine to receive subcutaneous fremanezumab monthly (225 mg at baseline, week 4, and week 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 12-week treatment period after the first dose.ResultsOf 357 patients enrolled (safety set, n = 356; full analysis set, n = 354), the least-squares mean (±standard error) reductions in the average number of migraine days per month during 12 weeks were significantly greater with fremanezumab monthly (-4.0 ± 0.4, n = 121) and fremanezumab quarterly (-4.0 ± 0.4, n = 117) than with placebo (-1.0 ± 0.4, n = 116; p < 0.0001 for both comparisons). The proportion of patients reaching at least a 50% reduction in the monthly average number of migraine days during the 12-week period after initial administration was also significantly improved with fremanezumab (fremanezumab monthly, 41.3%; fremanezumab quarterly, 45.3%; placebo, 11.2%; p < 0.0001 for both comparisons) as were other secondary endpoints (p < 0.001 for all comparisons between fremanezumab and placebo). Injection-site reactions were more common in fremanezumab-treated patients (fremanezumab monthly, 25.6%; fremanezumab quarterly, 29.7%; placebo, 21.4%).ConclusionFremanezumab prevents episodic migraine in Japanese and Korean patients to a similar extent than in previously reported populations with no new safety concerns.

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