14 CLINICAL STUDIES

The efficacy of UBRELVY for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials [Study 1 (NCT02828020) and Study 2 (NCT02867709)]. Study 1 randomized patients to placebo (n=559) or UBRELVY 50 mg (n=556) or 100 mg (n=557) and Study 2 randomized patients to placebo (n=563) or UBRELVY 50 mg (n=562). In all studies, patients were instructed to treat a migraine with moderate to severe headache pain intensity. A second dose of study medication (UBRELVY or placebo), or the patient’s usual acute treatment for migraine, was allowed between 2 to 48 hours after the initial treatment for a non-responding or recurrent migraine headache. Up to 23% of patients were taking preventive medications for migraine at baseline. None of these patients were on concomitant preventive medication that act on the CGRP pathway.

The primary efficacy analyses were conducted in patients who treated a migraine with moderate to severe pain. The efficacy of UBRELVY was established by an effect on pain freedom at 2 hours post-dose and most bothersome symptom (MBS) freedom at 2 hours post-dose, compared to placebo, for Studies 1 and 2. Pain freedom was defined as a reduction of moderate or severe headache pain to no pain, and MBS freedom was defined as the absence of the self-identified MBS (i.e., photophobia, phonophobia, or nausea). Among patients who selected an MBS, the most commonly selected was photophobia (56%), followed by phonophobia (24%), and nausea (19%).

In both studies, the percentage of patients achieving headache pain freedom and MBS freedom 2 hours post-dose was significantly greater among patients receiving UBRELVY compared to those receiving placebo (see Table 3). Table 3 also presents the results of the analyses of the percentage of patients achieving pain relief at 2 hours (defined as a reduction in migraine pain from moderate or severe to mild or none) post-dose and the percentage of patients achieving sustained pain freedom between 2 to 24 hours post-dose.

The incidence of photophobia and phonophobia was reduced following administration of UBRELVY at both doses (50 mg and 100 mg) as compared to placebo.

Table 3: Migraine Efficacy Endpoints for Study 1 and Study 2
	Study 1			Study 2
	UBRELVY 50 mg	UBRELVY 100 mg	Placebo	UBRELVY 50 mg	Placebo
Pain Free at 2 hours
N	422	448	456	464	456
% Responders	19.2	21.2	11.8	21.8	14.3
Difference from placebo (%)	7.4	9.4		7.5
p value	0.002	<0.001		0.007
Most Bothersome Symptom Free at 2 hours
N	420	448	454	463	456
% Responders	38.6	37.7	27.8	38.9	27.4
Difference from placebo (%)	10.8	9.9		11.5
p value	<0.001	<0.001		<0.001
Pain Relief at 2 hours
N	422	448	456	464	456
% Responders	60.7	61.4	49.1	62.7	48.2
p value	<0.001	<0.001		<0.001
Sustained Pain Freedom 2-24 hours
N	418	441	452	457	451
% Responders	12.7	15.4	8.6	14.4	8.2
p value	*NS	0.002		0.005

* Not statistically significant (NS)

Figure 1 presents the percentage of patients achieving migraine pain freedom within 2 hours following treatment in Studies 1 and 2.

Figure 1: Percentage of Patients Achieving Pain Freedom within 2 Hours in Pooled Studies 1 and 2

Figure 1: Percentage of Patients Achieving Pain Freedom within 2 Hours in Pooled Studies 1 and 2

a The 100 mg arm was only included in Study 1.

Figure 2 presents the percentage of patients achieving MBS freedom within 2 hours in Studies 1 and 2.

Figure 2: Percentage of Patients Achieving MBS Freedom within 2 Hours in Pooled Studies 1 and 2

Figure 2: Percentage of Patients Achieving MBS Freedom within 2 Hours in Pooled Studies 1 and 2

a The 100 mg arm was only included in Study 1.