Patients with episodic migraines had significantly fewer headache days when treated with a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), results of a recent randomized clinical trial show.
The treatment was generally well tolerated, and also improved secondary efficacy outcomes; however, the investigators qualified the results, noting that the trial included patients who had failed two or fewer previous classes of migraine preventive medication.
“Further research is needed to assess effectiveness against other preventive medications, and in patients in whom multiple preventive drug classes have failed,” wrote, of Mayo Clinic, Phoenix, Ariz., and his coauthors. Long-term safety and efficacy also are needed, they added. Their report was published in .
Fremanezumab is a subcutaneously administered, fully humanized monoclonal antibody that binds to the CGRP ligand. A previous randomized phase 2b study showed that the treatment was effective in preventing migraine, with no serious treatment-related adverse events.
The current 12-week phase 3 trial (clinicaltrials.gov Identifier: ) was designed to evaluate the efficacy and safety of fremanezumab in two different dosing regimens. A total of 875 patients (742 women; 85%) with episodic migraine were randomly assigned to fremanezumab monthly dosing (225 mg at baseline, 4 weeks, and 8 weeks), a single higher dose of fremanezumab (675 mg at baseline) intended to support a quarterly dosing regimen, or placebo.
Both dosing approaches significantly reduced the mean number of migraine days per month vs. placebo, Dr. Dodick and his coinvestigators reported.
In the monthly dosing group, the mean number of migraine days per month decreased from 8.9 to 4.9, and compared with placebo (with a decrease from 9.1 to 6.5 days), the mean number of migraine days at 12 weeks was 1.5 days lower (P less than .001). Similarly, the mean number of migraine days decreased from 9.2 to 5.3 days in the single higher dose group, with a difference of 1.3 days vs. placebo (P less than .001).
Significantly more patients receiving fremanezumab had a 50% or greater reduction in mean number of migraine days per month, suggesting a clinical response to the CGRP monoclonal antibody, the investigators said.
The most common adverse events leading to discontinuation included erythema at the injection site in three patients, along with induration, diarrhea, anxiety, and depression occurring in two patients each, according to the report. There was one death in the study due to suicide 109 days after the patient received a single higher dose of the study drug. However, the investigators determined that the death was unrelated to treatment.
One limitation of the study, investigators said, is that it excluded patients with treatment refractory migraine who had failed at least two previous preventive drug classes, and those who had continuous headache.
“Further studies are needed to define the full spectrum of efficacy and tolerability of fremanezumab, including in patients who are treatment refractory and who have a range of coexistent diseases,” they wrote.
Teva Pharmaceuticals supported the study. Dr. Dodick and his coauthors reported disclosures related to Teva, Amgen, Novartis, Pfizer, and Merck, among other entities.
SOURCE: Dodick DW et al. .