Efficacy and Safety of Fremanezumab Consistent in Patients With Migraine and Obesity

Pablo Irimia Siera, MD

In a post-hoc analysis of the phase 3 HALO-LTS study (NCT02638103) and phase 3b FOCUS trial (NCT03308968), treatment with fremanezumab (Ajovy; Teva Pharmaceuticals), an FDA-approved migraine medication, was efficacious and well tolerated over a 6-month period in patients with both migraine and obesity. The data was consistent with previous fremanezumab studies and support the use of this agent for migraine prevention in a wide population of patients.¹

HALO-LTS and FOCUS were 2 randomized, placebo-controlled trials that features patients with episodic (EM) or chronic migraine (CM) who were randomly assigned to receive either monthly (CM: 675/225/225 mg; EM: 225/225/225 mg) or quarterly (675 mg) fremanezumab, or monthly matched placebo during the respective treatment periods. The analysis, presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, featured 2437 patients from the studies who received fremanezumab, 578 of which had high body mass index (BMI) and 1859 with normal BMI (<30 kg/m2).

Despite BMI-high patients having more self-reported comorbidities, these individuals reported a greater change in monthly migraine days (MMDs), the primary end point, vs BMI-normal patients (–6.9 vs –5.9) at month 6 in HALO-LTS. Led by Pablo Irimia Siera, MD, a specialist in neurology at the Clinica Universidad de Navarra, similar proportions of patients experienced adverse events (AEs) in the BMI-high (n = 462; 80%) and BMI-normal (n = 1459; 78%) subgroups.

Obesity and migraine are highly prevalent conditions in the general population. Some studies have shown a relationship between obesity and various features of migraine including higher frequency, aura, and increased frequency of photophobia and phonophobia. Furthermore, obesity may have an association with various cardiovascular comorbidities seen with migraine.

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In BMI-high and BMI-normal subgroups, mean headache days were 13.2 vs 13.4 at baseline, and 7.0 vs 7.4 at month 6, with a mean change from baseline of –6.2 vs –5.6 at month 6. Overall, investigators concluded that fremanezumab, a calcitonin gene-related peptide (CGRP)-targeting therapy, was efficacious and safe over a 6-month period as a migraine preventive regardless of patients BMI.

Fremanezumab is indicated for prophylaxis of migraine in adults who have at least 4 migraine days per month. The therapy is available as a 225 mg/1.5 mL single dose injection in a pre-filled syringe or, in some countries, a pre-filled pen. Two dosing options are available: 225 mg once monthly administered as 1 subcutaneous injection (monthly dosing), or 675 mg every 3 months (quarterly dosing), which is administered as 3 subcutaneous injections.

Days before the 2024 AAN Annual Meeting, Teva announced results from a phase 3 study evaluating the efficacy and safety of fremanezumab for the prevention of migraine in adult Chinese patients. In the study, which featured 365 adults with migraine, the CGRP-targeting therapy met its primary end point and all secondary end points, significantly reducing the number of migraine days experienced per month, demonstrating superior efficacy over placebo.

In the trial, patients were randomly assigned to receive a subcutaneous injection of fremanezumab once-monthly or once-quarterly, or placebo, in a 1:1:2 ratio. All key secondary end points were also met including measures for early onset of efficacy during the first month, responder rate analysis defined as 50% reduction of migraine days and reduction of acute headache medication use over 3 months after first use. In addition, the therapy was safe and well tolerated, with data that was consistent with the previous phase 3 study for which fremanezumab was approved as a preventive treatment in the US in 2018.

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REFERENCES
1. Sieira PI, Torphy B, Ortega M, et al. Efficacy and safety of fremanezumab in patients with migraine and obesity: a post hoc analysis of the phase 3 HALO-LTS and FOCUS clinical trials. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. ABSTRACT 005428
2. Teva confirms efficacy and safety of Ajovy (Fremanezumab) for the prevention of migraine with results from phase 3 trial in China. News release. Teva Pharmaceuticals. April 11, 2024. Accessed April 16, 2024. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2024/Teva-Confirms-Efficacy-and-Safety-of-AJOVY-fremanezumab-for-the-Prevention-of-Migraine-With-Results-from-Phase-3-Trial-in-China/default.aspx