Galcanezumab Demonstrates Promise as Therapy for Vestibular Migraine

Jeffrey D. Sharon, MD

Recently published findings from the INVESTMENT study, a placebo-controlled, randomized clinical trial, showed that treatment with galcanezumab (Emgality; Eli Lilly), an FDA-approved calcitonin gene-related peptide (CGRP)-blocking medication, was effective in treating patients with vestibular migraine (VM). Over a 3-month treatment period, those on the medication demonstrated improvements in definite dizzy days (DDDs), dizziness handicap, and VM disease severity relative to placebo.

Considered the first randomized, controlled trial testing a CGRP-blocking medication for vestibular migraine (VM), the pilot study comprised of 40 patients with the disease who were randomized 1:1 to galcanezumab or placebo for a 3-month treatment period. Overall, the modified intent to treat (mITT) population included 38 patients who received 240 mg worth of treatment in the first month, followed by 120 mg doses for the second and third months. Most participants were female (75%), with a diagnosis of VM per Barany Society criteria (88%), and White (75%), with a history of migraine headaches (93%).

Led by Jeffrey D. Sharon, MD, an assistant professor in the Otology, Neurotology, and Skull Base Surgery division at UCSF Health, the study used change in Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) score as the primary end point, with changes in Dizziness Handicap Inventory (DHI) score and count of DDDs as secondary outcomes. After 3 months of treatment, those in the placebo group dropped 5.1 points (95% CI, –13.0 to 2.7) on VM-PATHI while those in the galcanezumab group experienced a drop of 14.8 points (95% CI, –23.0 to –6.5), which was considered statistically significant on one-tailed t-test(P = .044) but not with a 2-tailed test (P = .087).

In the study, patients in the placebo arm showed a mean reduction of 8.3 points (95% CI, –15.0 to 1.6) on DHI score while those on galcanezumab had a reduction of 22.0 points (95% CI, –31.9 to –12.1). The difference of 14.4 points was considered statistically significant (P = .018), with a large effect size (Cohen’s d = .98). Additionally, investigators observed significant decreases in number of DDDs, with those on active treatment dropping from 17.9 to 6.6 (P = .026) at month 4 and those on placebo dropping from 18.0 to 12.5.

READ MORE: Migraine Medication Symbravo Demonstrates Therapeutic Efficacy in Patients Unresponsive to CGRPs

"Large, prospective, placebo controlled randomized clinical trials are required to further investigate the efficacy of various migraine treatments for VM,” Sharon et al wrote. "In addition to the obvious benefits of ascertaining which treatments are effective, this would also help with educating the public and medical personnel regarding this common disease. Furthermore, there are still fundamental questions regarding the relationship of VM to migraine headaches. This study adds to a body of evidence that VM is just another form of migraine and that the pathophysiology involves CGRP."

Patients in the galcanezumab arm showed greater improvements in both the mental and physical subscales of the Patient Reported Outcome Measurement Information System (PROMIS) Global Health v1.2, though the differences were not statistically significant. On the physical subscale, t-scores increased by 5.3 points (95% CI 1.7 to 8.9) in the galcanezumab group compared to 1.9 points (95% CI −0.97 to 4.8) in the placebo group (P = 0.129). Similarly, on the mental subscale, the galcanezumab group saw an increase of 4.8 points (95% CI 2.1 to 7.5), while the placebo group increased by 3.2 points (95% CI −0.58 to 7.0; P = 0.494).

At the final visit, participants rated medication effectiveness on a scale from 0 ("not at all") to 4 ("I felt cured"). Investigators recorded a mean score of 2.1 (SD, 1.1) in the galcanezumab group vs a mean score of 1.0 (SD, 1.2) for the placebo group, leading to an effect size of 0.89 on Cohen’s d. Overall, 71% of those on active treatment had a moderate or greater treatment effect, compared with 24% of those in the placebo arm (chi-squared test, P = .004).

This study had several limitations, including its early termination due to the sponsor halting medication supply, which affected three participants, and a pharmacist error that led to two participants being crossed over between treatment arms. It was also a small, single-center study without pre- and post-intervention vestibular testing, limiting insights into CGRP’s role in VM. Despite these issues, its strengths include a double-blind, placebo-controlled design, robust daily data collection via text messaging, and consistent results across multiple outcome measures, such as the DHI and VM-PATHI, which highlight the potential benefit of CGRP blockade in VM while emphasizing the need for larger, multi-center trials.

REFERENCE
1. Sharon JD, Krauter R, Chae R, et al. A placebo controlled, randomized clinical trial of galcanezumab for vestibular migraine: The INVESTMENT study. Headache. 2024;64(10):1264-1272. doi:10.1111/head.14835