Once-monthly galcanezumab for the prevention of migraine in adults: an evidence-based descriptive review and potential place in therapy

Figures & data

Table 1 EVOLVE-1 and EVOLVE-2 studies: primary and key secondary efficacy endpoints (least-squares mean change from baseline or estimated percentage) over months 1–6

	EVOLVE-1 study			EVOLVE-2 study
	Placebo (n=425)	Galcanezumab 120 mg (n=210)	Galcanezumab 240 mg (n=208)	Placebo (n=461)	Galcanezumab 120 mg (n=231)	Galcanezumab 240 mg (n=223)
Primary endpoint
Monthly MHD	−2.8	−4.7	−4.6	−2.3	−4.3	−4.2
P-value vs placeboa		<0.001 (S)	<0.001 (S)		<0.001 (S)	<0.001 (S)
Key secondary endpoints
≥50% response	38.6	62.3	60.9	36	59.3	56.5
P-value vs placeboa		<0.001 (S)	<0.001 (S)		<0.001 (S)	<0.001 (S)
≥75% response	19.3	38.8	38.5	17.8	33.5	34.3
P-value vs placeboa		<0.001 (S)	<0.001 (S)		<0.001 (S)	<0.001 (S)
100% response	6.2	15.6	14.6	5.7	11.5	13.8
P-value vs placeboa		<0.001 (S)	<0.001 (S)		<0.001 (S)	<0.001 (S)
Monthly MHD with acute medication use	−2.2	−4.0	−3.8	−1.9	−3.7	−3.6
P-value vs placeboa		<0.001 (S)	<0.001 (S)		<0.001 (S)	<0.001 (S)

Note:

a P-value indicates nominal significance without multiplicity adjustment.

Abbreviations: MHD, migraine headache days; S, significant after multiplicity adjustment.

Table 2 REGAIN study: primary and key secondary efficacy endpoints (least-squares mean change from baseline or estimated percentage) over months 1–3

	Placebo (n=538)	Galcanezumab 120 mg (n=273)	Galcanezumab 240 mg (n=274)
Primary endpoint
Monthly MHD	−2.7	−4.8	−4.6 (0.4)
P-value vs placeboa		<0.001 (S)	<0.001 (S)
Key secondary endpoints
≥50% response	15.4	27.6	27.5
P-value vs placeboa		<0.001 (S)	<0.001 (S)
≥75% response	4.5	7.0	8.8
P-value vs placeboa		0.031 (NS)	<0.001 (S)
100% response	0.5	0.7	1.3
P-value vs placeboa		0.597 (NS)b	0.058 (NS)
Monthly MHD with acute medication use	−2.2	−4.7	−4.3
P-value vs placeboa		<0.001 (NS)b	<0.001 (S)

Notes:

a P-value indicates nominal significance without multiplicity adjustment.

b Item not tested after all α expended on previous items in multiplicity adjustment testing sequence. It is considered not statistically significant regardless of P-value.

Abbreviations: MHD, migraine headache days; NS, not significant after multiplicity adjustment; S, significant after multiplicity adjustment.

Table 3 Additional Phase II and III clinical trials of galcanezumab

Main identifier(s)	Condition	Phase	Study status	Location(s)
(NCT02959177) I5Q-JE-CGAN	EM, adults	II	Active, not recruiting	Japan
(NCT02959190) I5Q-JE-CGAP	EM/CM, adults	III	Active, not recruiting	Japan
(NCT03559257) I5Q-MC-CGAW CONQUER	EM/CM, therapy-resistant adults	III	Recruiting	Multinational
(NCT03432286) I5Q-MC-CGAS REBUILD	EM, participants 6–17 years of age	III	Recruiting	USA, Puerto Rico
(NCT02397473) I5Q-MC-CGAL	ECH, adults	III	Completed	Multinational
(NCT02438826) I5Q-MC-CGAM	CCH, adults	III	Active, not recruiting	Multinational
(NCT02797951) I5Q-MC-CGAR	ECH or CCH, adults who completed I5Q-MC-CGAL/I5Q-MC-CGAM	IIIb	Enrolling by invitation	Multinational

Abbreviations: CCH, chronic cluster headache; CM, chronic migraine; ECH, episodic cluster headache; EM, episodic migraine.

Table 4 Overview of adverse events in EVOLVE-1, EVOLVE-2, and REGAIN trials

AEs
EVOLVE-1	Placebo (n=432)	Galcanezumab 120 mg (n=206)	Galcanezumab 240 mg (n=220)
TAEs	261 (60.4%)	135 (65.5%)	149 (67.7%)
SAEs	5 (1.2%)	7 (3.4%)	0 (0%)
Deaths	0 (0%)	0 (0%)	0 (0%)
Discontinuation due to AEs	10 (2.3%)	9 (4.4%)	7 (3.2%)
EVOLVE-2	Placebo (n=461)	Galcanezumab 120 mg (n=226)	Galcanezumab 240 mg (n=228)
TAEs	287 (62.3%)	147 (65%)	163 (71.5%)a
SAEs	5 (1.1%)	5 (2.2%)	7 (3.1)
Deaths	0 (0.0%)	0 (0%)	0 (0%)
Discontinuation due to AEs	8 (1.7%)	5 (2.2%)	9 (4%)
REGAIN	Placebo (n=558)	Galcanezumab 120 mg (n=273)	Galcanezumab 240 mg (n=282)
TAEs	279 (50%)	158 (58%)a	160 (57%)
SAEs	4 (0.7%)	1 (0.4%)	5 (1.8%)
Deaths	0 (0%)	0 (0%)	0 (0%)
Discontinuation due to AEs	6 (1.1%)	1 (0.4%)	4 (1.4%)

Note:

a P<0.05 vs placebo.

Abbreviations: AE, adverse event; SAE, serious adverse event; TAE, treatment-emergent adverse event.

Table 5 Main treatment-emergent adverse events reported by at least 2% of galcanezumab-treated patients in EVOLVE-1, EVOLVE-2, and REGAIN trials

TAEs
EVOLVE-1	Placebo (n=432)	Galcanezumab 120 mg (n=206)	Galcanezumab 240 mg (n=220)
Patients with ≥1 TAE	261 (60.4%)	135 (65.5%)	149 (67.7%)
Injection-site pain	75 (17.4%)	33 (16%)	45 (20.5%)
Nasopharyngitis	27 (6.3%)	16 (7.8)	6 (2.7%)
Urinary tract infections	15 (3.5%)	8 (3.9)	13 (5.9%)
Injection-site reaction	4 (0.9%)	7 (3.4)a	12 (5.5%)a
Injection-site erythema	11 (2.6%)	10 (4.9)	9 (4.1%)
Injection-site pruritus	1 (0.2%)	9 (4.4)a	10 (4.6%)a
EVOLVE-2	Placebo (n=461)	Galcanezumab 120 mg (n=226)	Galcanezumab 240 mg (n=228)
Patients with ≥1 TAE	287 (62.3%)	147 (65%)	163 (71.5%)a
Injection-site pain	39 (8.5%)	21 (9.3%)	20 (8.8%)
Nasopharyngitis	41 (8.9%)	19 (8.4%)	16 (7%)
Upper respiratory tract infections	16 (3.5%)	13 (5.8%)	12 (5.3%)
Injection-site reaction	0 (0%)	7 (3.1%)a	18 (7.9%)a
Injection-site erythema	4 (0.9)	6 (2.7%)	7 (3.1%)a
Injection-site pruritus	0 (0%)	6 (2.7%)a	7 (3.1%)a
REGAIN	Placebo (n=558)	Galcanezumab 120 mg (n=273)	Galcanezumab 240 mg (n=282)
Patients with ≥1 TAE	279 (50%)	159 (58%)a	160 (57%)
Injection-site pain	24 (4%)	17 (6%)	20 (7%)
Nasopharyngitis	26 (5%)	17 (6%)	9 (3%)
Upper respiratory tract infections	13 (2%)	9 (3%)	9 (3%)
Injection-site reaction	10 (2%)	8 (3%)	15 (5%)b
Injection-site erythema	5 (1%)	4 (1%)	13 (5%)c,d
Injection-site pruritus	1 (0%)	0 (0%)	7 (2%)c,d

Notes:

a P<0.05 vs placebo.

b P<0.01 vs placebo.

c P<0.001 vs placebo.

d P<0.05 vs galcanezumab.

Abbreviation: TAE, treatment-emergent adverse event.