Fremanezumab Efficacy Shows Consistency Across Monthly, Quarterly Dosing Regimens

October 16, 2020

Decreases in weekly migraine days remained steady during the last 2 weeks of the first quarter, with a similar maintenance of response during the second quarter.

Post-hoc analysis results from a 15-month study period that included patients with chronic (CM) and episodic migraine (EM) demonstrated that treatment with either monthly or quarterly fremanezumab (Ajovy; Teva Pharmaceuticals) dosing did not show a wear-off effect towards the end of the dosing interval.1,2

The analysis included 1043 patients with CM (n = 611) and EM (n = 432) in a long-term, 12-month phase 3 study (NCT02638103) who were initially enrolled in the HALO CM (NCT02621931) and HALO EM trials (NCT02629861) and were double-blinded to monthly or quarterly fremanezumab.

At months 3, 6, 9, and 15, there were no substantial differences in mean weekly migraine days between weeks 1–2 and weeks 3–4 or between weeks 1–3 and week 4 with quarterly or monthly fremanezumab in the CM or EM subgroups.

"This is an important analysis for the migraine community since clinical symptoms often return or worsen before the next dose of many preventive migraine medications is due,” Andrew Blumenfeld, MD, director, Headache Center of Southern California, said in a statement.

In the first quarter, patients with CM on quarterly dosing experienced a mean number of 2.8 and 2.7 weekly migraine days in weeks 1–2 and weeks 11–12, respectively, compared to 2.5 and 2.5 weekly migraine days in those respective weeks during the second quarter.

Similar results were shown for those with EM. A total of 1.5 and 1.3 mean weekly migraine days were reported in weeks 1–2 versus weeks 11–12 in the first quarter decreased to 1.2 and 1.1 weekly migraine days, respectively, in weeks 1–2 and weeks 11–12 in the second quarter.

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Patients with CM who took monthly fremanezumab reported a mean number of 2.6 migraine days during weeks 1–3 at the beginning of dosing, which decreased to 1.8 at week 4 at the end of the 15-month treatment period. Within that time period, there were no statistically significant differences between weeks 1–3 and week 4 during any of the 3-month intervals.

Patients with EM on monthly fremanezumab experienced a mean number of 1.2 weekly migraine days in weeks 1–3 after initiation and 1.0 mean number of weekly migraine days in week 4 at the end of the study period.

During the first 2 weeks of fremanezumab quarterly and monthly treatment decreases of approximately 31% and 30% weekly migraine days from baseline were observed for patients with CM, respectively, as well as decreases of approximately 37% and 42% in patients with EM.

For context, the mean weekly number of migraine days at baseline was 4.0 for patients with CM taking quarterly or monthly fremanezumab. Among patients with EM, the mean weekly number of migraine days at baseline in the quarterly and monthly fremanezumab groups were both 2.3 days.

"Migraine can be a debilitating disease, so evaluating migraine days throughout a dosing regimen can be significant for healthcare providers when considering treatment options. Whenever the brain is exposed to a migraine attack, there is the possibility of increased sensitization with progressive worsening of the frequency of migraine. A key clinical goal is to limit the amount of time the brain is exposed to migraine to reduce this risk and the number of migraine days impacting a patient before their next dose,” Blumenfeld added.

Across both dosing subgroups in patients with CM and EM, the mean weekly number of migraine days decreased by 30% to 42% during the first 2 weeks. Investigators noted that decreases in weekly migraine days remained steady during the last 2 weeks of the first quarter, with a similar maintenance of response during the second quarter.

No new safety signals were identified in this population that were inconsistent with the known safety profile of fremanezumab. The most commonly reported adverse events (AEs) were injection-site reactions, with similar incidence rates between treatment groups. Among those injection-site reactions, induration (CM quarterly, 30%; CM monthly, 35%; EM quarterly, 29%; EM monthly, 38%), injection-site pain (29%, 33%, 30%, and 32%, respectively), and injection-site erythema (25%, 31%, 22%, and 27%, respectively) were the most common types.

In September 2018, the FDA approved fremanezumab for the prevention of migraine in adults. At the time, the drug was made available for administration via a prefilled syringe indicated for 1-time use.3 An autoinjector for the delivery of fremanezumab was approved by the FDA in January of this year.4

REFERENCES
1. Teva announces new analysis of consistency in migraine days over the course of a dosing regimen for Ajovy (fremanezumab-vfrm) injection published in headache. News release. Teva Pharmaceuticals. October 7, 2020. Accessed October 15, 2020. https://www.tevausa.com/news-and-media/press-releases/teva-announces-new-analysis-of-consistency-in-migraine-days-over-the-course-of-a-dosing-regimen-for-ajovy/
2. Blumenfeld AM, Stevanovic DM, Ortega M, et al. No ‘wearing-off effect’ seen in quarterly or monthly dosing of fremanezumab: sub-analysis of a randomized long-term study. Headache. Published October 2, 2020. doi: 10.1111/head.13994
3. Teva Announces U.S. Approval of AJOVYTM (fremanezumab-vfrm) Injection, the First and Only Anti-CGRP Treatment with Both Quarterly and Monthly Dosing for the Preventive Treatment of Migraine in Adults. News release. Teva Pharmaceutical.Published September 2018. Accessed October 15, 2020. https://www.businesswire.com/news/home/20180914005613/en/Teva-Announces-U.S.-Approval-AJOVYTM-fremanezumab-vfrm-Injection.
4. Teva announces FDA approval of ajovy (fremanezumab-vfrm) injection autoinjector. News release. Teva Pharmaceuticals. January 28, 2020. Accessed October 15, 2020. businesswire.com/news/home/20200128005810/en.