14 CLINICAL STUDIES

The efficacy of AJOVY was evaluated as a preventive treatment of episodic or chronic migraine in two multicenter, randomized, 3-month, double-blind, placebo-controlled studies (Study 1 and Study 2, respectively).

Episodic Migraine

Study 1 (NCT 02629861) included adults with a history of episodic migraine (patients with <15 headache days per month). All patients were randomized (1:1:1) to receive subcutaneous injections of either AJOVY 675 mg every three months (quarterly), AJOVY 225 mg monthly, or placebo monthly, over a 3-month treatment period. Patients were allowed to use acute headache treatments during the study. A subset of patients (21%) was allowed to use one additional concomitant preventive medication.

The study excluded patients with a history of significant cardiovascular disease, vascular ischemia, or thrombotic events, such as cerebrovascular accident, transient ischemic attacks, deep vein thrombosis, or pulmonary embolism.

The primary efficacy endpoint was the mean change from baseline in the monthly average number of migraine days during the 3-month treatment period. Secondary endpoints included the proportion of patients reaching at least a 50% reduction in monthly average number of migraine days during the 3-month treatment period, the mean change from baseline in the monthly average number of days of use of any acute headache medication during the 3-month treatment period, and the mean change from baseline in the number of migraine days during the first month of the treatment period.

In Study 1, a total of 875 patients (742 females, 133 males), ranging in age from 18 to 70 years, were randomized. A total of 791 patients completed the 3-month double-blind phase. The mean migraine frequency at baseline was approximately 9 migraine days per month, and was similar across treatment groups.

Both monthly and quarterly dosing regimens of AJOVY demonstrated statistically significant improvements for efficacy endpoints compared to placebo over the 3-month period, as summarized in Table 2.

Table 2: Efficacy Endpoints in Study 1
Study 1 Efficacy Endpoint	AJOVY 225 mg Monthly (N=287)	AJOVY 675 mg Quarterly (N=288)	Placebo (N=290)
Monthly migraine days (MMD)
Baseline migraine days	8.9	9.2	9.1
Change from baseline	-3.7	-3.4	-2.2
Difference from placebo	-1.5	-1.2
p-value	<0.001	<0.001
≥50% MMD responders
% responders	47.7%	44.4%	27.9%
Difference from placebo	19.8%	16.5%
p-value	<0.001	<0.001
Monthly acute headache medication days
Change from baseline	-3.0	-2.9	-1.6
Difference from placebo	-1.4	-1.3
p-value	<0.001	<0.001

Figure 1 displays the mean change from baseline in the average monthly number of migraine days in Study 1.

Figure 1: Change from Baseline in Monthly Migraine Days in Study 1a

Figure 2 shows the distribution of change from baseline in mean monthly migraine days in bins of 2 days by treatment group in Study 1. A treatment benefit over placebo for both doses of AJOVY is seen across a range of changes from baseline in monthly migraine days.

Figure 2: Distribution of Change from Baseline in Mean Monthly Migraine Days by Treatment Group in Study 1

Chronic Migraine

Study 2 (NCT 02621931) included adults with a history of chronic migraine (patients with ≥15 headache days per month). All patients were randomized (1:1:1) to receive subcutaneous injections of either AJOVY 675 mg starting dose followed by 225 mg monthly, 675 mg every 3 months (quarterly), or placebo monthly, over a 3-month treatment period. Patients were allowed to use acute headache treatments during the study. A subset of patients (21%) was allowed to use one additional concomitant, preventive medication.

The study excluded patients with a history of significant cardiovascular disease, vascular ischemia, or thrombotic events, such as cerebrovascular accident, transient ischemic attacks, deep vein thrombosis, or pulmonary embolism.

The primary efficacy endpoint was the mean change from baseline in the monthly average number of headache days of at least moderate severity during the 3-month treatment period. The secondary endpoints were the mean change from baseline in the monthly average number of migraine days during the 3-month treatment period, the proportion of patients reaching at least 50% reduction in the monthly average number of headache days of at least moderate severity during the 3-month treatment period, the mean change from baseline in the monthly average number of days of use of any acute headache medication during the 3-month treatment period, and the mean change from baseline in the number of headache days of at least moderate severity during the first month of treatment.

In Study 2, a total of 1130 patients (991 females, 139 males), ranging in age from 18 to 70 years, were randomized. A total of 1034 patients completed the 3-month double-blind phase.

Both monthly and quarterly dosing regimens of AJOVY treatment demonstrated statistically significant improvement for key efficacy outcomes compared to placebo, as summarized in Table 3.

Table 3: Efficacy Endpoints in Study 2
Study 2 Efficacy Endpoint	AJOVY 225 mga Monthly (N=375)	AJOVY 675 mg Quarterly (N=375)	Placebo (N=371)
Baseline headache days of any severityb	20.3	20.4	20.3
Baseline headache days of at least moderate severityc	12.8	13.2	13.3
Change from baseline in the monthly average number of headache days of at least moderate severity	-4.6	-4.3	-2.5
Difference from placebo	-2.1	-1.8
p-value	<0.001	<0.001
Change from baseline in the monthly average number of migraine days in patients	-5.0	-4.9	-3.2
Change from baseline in monthly average number of headache days of at least moderate severity at 4 weeks after 1st dose	-4.6	-4.6	-2.3
Percentage of patients with ≥ 50% reduction in monthly average number of headache days of at least moderate severity	40.8%	37.6%	18.1%
Change from baseline in monthly average number of days of acute headache medication	-4.2	-3.7	-1.9

aIn Study 2, patients received a 675 mg starting dose.
bUsed for chronic migraine diagnosis.
cUsed for primary endpoint analysis.

Figure 3 displays the mean change from baseline in the average monthly number of headache days of at least moderate severity in Study 2.

Figure 3: Change from Baseline in Monthly Headache Days of At Least Moderate Severity in Study 2a

Figure 4 shows the distribution of change from baseline in monthly headache days of at least moderate severity at month 3 in bins of 3 days by treatment group. A treatment benefit over placebo for both dosing regimens of AJOVY is seen across a range of changes from baseline in headache days.

Figure 4: Distribution of Mean Change from Baseline in Monthly Headache Days of At Least Moderate Severity by Treatment Group in Study 2

*In Study 2, patients received a 675 mg starting dose.