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(2018)Objective
Galcanezumab - To evaluate the efficacy and safety of galcanezumab (120 mg or 240 mg) for the prevention of episodic migraine.
Study Summary
• Both doses showed rapid onset and sustained efficacy across 6 months.
• Galcanezumab improved migraine-related disability and functional outcomes.
• Common adverse effects were mild and included injection site reactions.
Intervention
Phase 3 randomized, double-blind, placebo-controlled trial. Patients with episodic migraine (4–14 MHDs/month) were randomized (2:1:1) to receive monthly galcanezumab 120 mg, 240 mg, or placebo. Primary endpoint: change in monthly MHDs. Secondary endpoints included ≥50%, ≥75%, and 100% responder rates, MSQ-RFR, PGI-S, MIDAS scores, and acute medication use.
Inclusion Criteria
Adults aged 18–65 years with 4–14 MHDs/month, migraine history ≥1 year, onset <50 years, and electronic diary compliance ≥80%.
Study Design
Arms: Galcanezumab 120 mg vs. Galcanezumab 240 mg vs. Placebo
Patients per Arm: 120 mg: 231; 240 mg: 223; Placebo: 461
Outcome
• ≥50% responders: 59% (120 mg), 57% (240 mg), 36% (placebo); p<0.001
• ≥75% responders: 33–34% (active) vs. 18% (placebo); p<0.001
• 100% responders: 12–14% (active) vs. 6% (placebo); p<0.001
• MSQ-RFR improvement: +28.5 (120 mg), +27.0 (240 mg) vs. +19.7 (placebo); p<0.001
• PGI-S score: -1.2 (120 mg), -1.2 (240 mg) vs. -0.9 (placebo); p<0.05
• MIDAS reduction at 6 months: -21.2 (120 mg), -20.2 (240 mg) vs. -12.0 (placebo); p<0.001
• TEAEs: mild injection site reactions were more frequent with galcanezumab (7–8%) but generally well tolerated.
Bottom Line
Galcanezumab 120 mg and 240 mg monthly were both significantly superior to placebo in reducing monthly migraine headache days, with a clinically meaningful reduction of approximately 2 additional days per month compared to placebo. Both doses were safe and well tolerated.
Major Points
- Phase 3, multicenter, double-blind, placebo-controlled RCT with 915 ITT patients across 109 sites in 11 countries
- Both galcanezumab doses reduced monthly MHDs by ~4.3 days vs 2.3 days for placebo (difference ~2 days/month)
- Majority achieved ≥50% response (59% and 57% vs 36%), representing clinically meaningful benefit
- Significant reductions in acute medication use, disability (MIDAS), and improvements in quality of life (MSQ RF-R)
- Most common adverse event was injection site pain (~9%), similar across groups; injection site reactions were more common with galcanezumab
- No deaths; SAEs were infrequent and not significantly different between groups
- Treatment-emergent anti-drug antibodies occurred more frequently with galcanezumab but did not impact efficacy or safety
- 85.8% completed the 6-month treatment phase
Study Design
- Study Type
- Phase 3, multicenter, double-blind, placebo-controlled, randomized clinical trial
- Randomization
- Yes
- Blinding
- Double-blind; galcanezumab and matching placebo supplied as visually indistinguishable single-dose prefilled syringes; all patients received two injections at each visit
- Sample Size
- 915
- Follow-up
- 6 months double-blind treatment
- Centers
- 109
- Countries
- United States, United Kingdom, Netherlands, Spain, Czech Republic, Germany, Argentina, Israel, Korea, Taiwan, Mexico
Primary Outcome
Definition: Overall mean change from baseline in the number of monthly migraine headache days during the 6-month double-blind treatment phase
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| −2.3 (SE 0.2) | - | - | <0.001 for both doses |
Limitations & Criticisms
- Exclusion of patients with serious medical/psychiatric conditions, high BMI, substantial opioid use, and high cardiovascular risk may limit generalizability
- 6-month duration may not detect rare adverse events or long-term risks
- Predominantly female (85%) and white (70%) population may not represent all migraine patients
- Patients who failed ≥3 preventive drug classes were excluded, limiting applicability to treatment-refractory patients
- No active comparator arm to assess relative efficacy vs existing preventive treatments
- Industry-sponsored trial with several authors as employees of Eli Lilly
Citation
Cephalalgia 2018; 38(8): 1442–1454