Assess 6-month efficacy and safety of galcanezumab in patients with treatment-resistant migraine.

Many patients who need migraine preventive treatment either do not respond to or cannot tolerate existing oral preventives and may end up cycling through multiple medications.

During double-blind treatment (Months 1-3), 462 patients (18-75 years) with episodic or chronic migraine and 2-4 previous migraine preventive medication category failures were randomized 1:1 to injections of placebo or galcanezumab 120mg/month (with 240-mg loading dose). After completing double-blind treatment, patients could enter an open-label extension (OLE; Months 4-6), in which all patients received galcanezumab 120mg/month. Primary endpoint was mean change from baseline in number of monthly migraine headache days. Key secondary endpoints included response rate (≥50% reduction in monthly migraine headache days) and mean change in Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score (MSQ-RFR). ­

Of 451 patients who completed double-blind treatment, 449 entered the OLE, with 432 (96%) completing. From a baseline (Month 0) of approximately 13 monthly migraine headache days, the mean change at Month 6 was -5.6 (prior galcanezumab group) and -5.2 (prior placebo group), with the prior placebo group showing a rapid reduction after first galcanezumab injection.   

At Month 6, approximately 54% of patients met the ≥50% response criterion. Of 87 galcanezumab-treated patients with ≥50% response at the end of double-blind treatment, 52% maintained that response throughout the OLE. Mean MSQ-RFR scores improved from baseline (score=45) to Month 6 by approximately 27 points on a 100-point scale.

The most common treatment-emergent adverse events during the OLE phase were nasopharyngitis (4.2%), injection-site pain (3.6%), and injection-site erythema (2.7%), with 5 patients (1.1%) discontinuing due to an adverse event. There were no clinically meaningful changes in any safety parameters.

Galcanezumab was effective, safe, and well-tolerated during the CONQUER open-label extension in patients with treatment-resistant migraine.