Fremanezumab Significantly Reduces in Depression in Patients With Migraine and Major Depressive Disorder

Richard B. Lipton, MD

Recent results from the phase 4 UNITE study (NCT04041284) showed that treatment with fremanezumab (Ajovy; Teva Pharmaceuticals) was associated with statistically significant reductions in depression among patients with migraine and major depressive disorder (MDD) over 8 weeks, maintaining effects at week 12 and beyond. These findings suggest that treatment with fremanezumab may be a beneficial option to reduce the symptoms and cumulative burden of migraine and depression in those diagnosed with both conditions.¹

At week 8 and 12, the mean change from baseline in Hamilton Depression Rating Scale-17 items (HAMD-17) score for placebo was –4.6 and –5.4, respectively, compared with –6.0 and –6.7 for fremanezumab (P = .0205; P = .0228). At the same time periods, the change from baseline in Patient Health Questionnaire-9 (PHQ-9) total score was –5.8 for placebo and –7.1 for fremanezumab (P = .0283) at week 8, and –6.3 for placebo and –7.8 for fremanezumab (P = .0108) at week 12.

The findings were presented at the 2023 American Headache Society (AHS) Annual Meeting, held June 15-18, in Austin, Texas, by lead author by Richard B. Lipton, MD, director of the Montefiore Headache Center. In the study, Lipton and colleagues investigated the efficacy of fremanezumab in reducing migraine and depression in patients with migraine and comorbid MDD. The authors noted that “depression is one of the most prevalent comorbidities in patients with migraine, and the collective burden of both disorders can decrease overall quality of life.”¹

The study was a 12-week multicenter, randomized, double-blind, placebo controlled, parallel-group trial that followed up with a 12-week open-label extension (OLE) period. There were 353 patients (episodic migraine, 48%; chronic migraine, 52%; mean age 42.9 years; women, 88%) diagnosed with MDD according to the DSM-V criteria at least 12 months prior to screening who were enrolled in the study. Patients also had active moderate-to-severe depressive symptoms, which were defined as a PHQ-9 score of at least 10 at screening. Exclusion criteria comprised of a diagnosis from a physician of bipolar disorder, psychotic features, catatonia, or suicidality.

Patients were permitted to have a single prescribed concomitant medication for depression if the dose had been stable for at least 8 weeks prior to screening and if no dose changes were expected during the study. Following a 4-week baseline period, patients were randomized 1:1 to receive either 225 mg of subcutaneous monthly fremanezumab (n = 175) or matched placebo (n = 178) for 12 weeks. All patients that continued into the 12-week OLE period were given 675 mg quarterly of fremanezumab.

The study key points were mean change from baseline in symptoms of depression from day 1 of randomization to week 8 after the first dose of the study treatment, which was measured by the HAMD-17 and the mean change from baseline in PHQ-9 scores. All told, “fremanezumab was not reported to impact on concomitant treatment that patients were receiving for symptoms of depression and there were no safety concerns.”¹

Fremanezumab, a fully humanized monoclonal antibody that selective targets the calcitonin gene-related peptide (CGRP), was FDA-approved in September 2018 for the prevention of migraine in adults. The approval was based on the supporting data from 2 studies in the phase III HALO (NCT02638103) clinical trial program. In the trials, fremanezumab reduced monthly migraine days by at least 50% in roughly 45% of patients with episodic migraine and about 40% of patients with chronic migraine in clinical trials. Originally, the treatment was approved as a prefilled syringe indicated for 1-time use, and in January 2020, it was approved by the FDA as an autoinjector for the delivery of fremanezumab, joining Amgen’s erenumab (Aimovig) and Eli Lilly’s galcanezumab (Emgality) as anti-CGRP agents available for administration through autoinjector.²

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REFERENCES
1. Lipton R, Barbanti P, Ramirez Campos V, et al. Efficacy of fremanezumab in reducing depression in patients with migraine and major depressive disorder: results of the UNITE study. Presented at: 2023 AHS Annual Meeting; June 15-18; Austin, TX. IO-05.
2. Teva announces FDA approval of ajovy (fremanezumab-vfrm) injection autoinjector. News release. Teva Pharmaceuticals. January 28, 2020. Accessed June 21, 2023. https://www.tevapharm.com/news-and-media/latest-news/teva-announces-fda-approval-of-ajovy-fremanezumab-vfrm-injection-autoinjector/