Bigal, Marcelo E.

Background In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migraine (CM). Objective Post-hoc analyses evaluated population-wise 50%, 75% and 100% responder rates, and the extent to which individual responders sustained a 50%, 75% and 100% reduction in migraine days, moderate-to-severe (M/S) headache days and days of acute medication use during all three treatment months of the fremanezumab phase 2 studies. Design/methods HFEM patients received either placebo or three once-monthly injections of 225 mg or 675 mg. CM patients received either placebo or three once-monthly injections of 900 mg, or an initial loading dose of 675 mg and subsequent injections of 225 mg. Patients reported headache-related data daily using an electronic diary. Results In the HFEM study, the percent of patients on fremanezumab doses 225 mg and 675 mg were greater compared to the percent of placebo patients with sustained 50% reduction in migraine days (39% and 35% vs. 10% for placebo, both p < 0.0001), M/S headache days (36% and 38% vs. 16% placebo, p = 0.0017 and p = 0.0007 respectively), and acute medication use days (36% and 27% vs. 8% placebo, p < 0.0001 and p = 0.0003). Likewise, although there were fewer patients with sustained 75% reduction, there were increases in the percent of patients on fremanezumab 225 mg and 675 mg in the HFEM study relative to placebo patients in migraine days (19% and 11% vs. 3% placebo, p = 0.0002 and p = 0.0176), M/S headache days (19% and 15% vs. 2% placebo, p = 0.0001 and p = 0.0011) and days of acute medication use (16% and 8% vs. 2% placebo, p = 0.0005 and p = 0.0377). In the CM study, there were increases in the percent of patients on fremanezumab 675/225 mg and 900 mg with 50% sustained reduction in M/S headache days (32% and 40% vs. 15% placebo, p = 0.0058 and p = 0.0002) and days of acute medication use (26% and 22% vs. 11% placebo, p = 0.0098 and p = 0.0492). There were also increases in the percent of patients on fremanezumab 675/225 mg and 900 mg compared to patients on placebo with 75% sustained reduction in M/S headache days (10% and 13% vs. 3%, p = 0.0665 and p = 0.0203). Few patients had 100% sustained reductions in these parameters in either study. Conclusions Post-hoc results must be interpreted with caution; nonetheless, a statistically significant percentage of patients who initially responded to fremanezumab within 1 month sustained this response over the subsequent 2 months. Sustained reduction in individual patients may provide a novel patient-centric, clinically meaningful endpoint for future trials assessing the effectiveness of preventive migraine treatments. Trials are registered as http://clinical trials.gov as NCT02025556 and NCT02021773.

Background Fremanezumab (formerly TEV‐48125) is a monoclonal antibody directed against calcitonin‐gene‐related peptide (CGRP), a validated target for migraine preventive therapy. In two previous phase 2 studies, fremanezumab administered once every 28 days for 12 weeks was found to be effective and safe as a preventive treatment for patients suffering from episodic migraine (EM) and chronic migraine (CM). Objective To evaluate the efficacy and safety of fremanezumab as an add‐on preventive therapy in individuals with EM and CM who are on stable doses of preventive migraine medications. Methods Two randomized placebo‐controlled studies tested once‐monthly subcutaneous injections of various dosing regimens of fremanezumab versus placebo in EM and CM. Headache information was captured daily using an electronic headache diary. For these post hoc analyses, data were pooled from patients who were on stable preventive medications and taking fremanezumab doses of 225 mg or 675/225 mg, or placebo. Results The sample consisted of 133 patients, (67 fremanezumab and 66 placebo). Total reduction in migraine days for the duration of the study was 12.4 for fremanezumab and 7.4 for placebo ( P = .0321). There were also decreases in moderate/severe headache days (12.5 vs 7.1, P = .0058), and days using acute medication for headaches relative to placebo (11.6 vs 7.5, P = .0414). Treatment emergent adverse events were generally mild and transient, and no serious adverse events were considered to be treatment‐related by the site investigators. Conclusions The findings from these post hoc analyses suggest that fremanezumab is a safe and effective add‐on treatment for migraine patients being concomitantly treated with other migraine preventive medications. Trials are registered at Clinicaltrials.gov NCT02025556 and NCT02021773.