Dataset Information

Eptinezumab Demonstrated Efficacy in Sustained Prevention of Episodic and Chronic Migraine Beginning on Day 1 After Dosing.

ABSTRACT:

Objective

To determine the onset of preventive efficacy with eptinezumab in patients with migraine.

Background

Eptinezumab is a monoclonal antibody inhibiting calcitonin gene-related peptide approved as an intravenously administered treatment for the prevention of migraine.

Methods

Patients who received eptinezumab 100 mg, eptinezumab 300 mg, or placebo in PROMISE7-1 (episodic migraine; 100 mg, n = 221; 300 mg, n = 222; placebo, n = 222) or PROMISE7-2 (chronic migraine; 100 mg, n = 356; 300 mg, n = 350; placebo, n = 366) were included. Testing of the percentage of patients with a migraine on day 1 after dosing was prespecified and alpha-controlled. In further exploration of this prespecified endpoint, a post hoc closed testing procedure, which controlled the false-positive (type 1) error rate, provided a statistically rigorous evaluation of migraine prevention onset. The procedure involved up to 84 tests of significance, all of which were performed in sequence until the first nonsignificant result.

Results

For both studies, all tests for significance for eptinezumab 100 and 300 mg, from days 1-84 through day 1 alone, achieved nominal significance (P < .05), indicating that eptinezumab was fully effective beginning on day 1. Over each interval, the treatment effect was comparable to the effect over weeks 1-12. Mean changes from baseline in monthly migraine days for the primary endpoint period ranged from -3.9 to -4.9, -4.1 to -4.9, and -2.2 to -3.2 for eptinezumab 100, 300 mg, and placebo, respectively, in PROMISE7-1 and from -7.2 to -8.0, -7.9 to -8.2, and -4.3 to -5.6, respectively, in PROMISE7-2. The difference from placebo (95% confidence interval) in day 1 treatment effect was -2.2 (-4.1, -0.3) and -2.5 (-4.4, -0.6) days/month for eptinezumab 100 and 300 mg, respectively, in PROMISE7-1, and was -3.8 (-5.6, -2.0) and -4.0 (-5.8, -2.1) days/month for 100 and 300 mg, respectively, in PROMISE7-2.

Conclusions

The migraine preventive effect of eptinezumab is rapid and sustained in patients with episodic or chronic migraine, with onset of optimal preventive efficacy observed on the day following the initial dose.

SUBMITTER: Dodick DW

PROVIDER: S-EPMC7756794 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Eptinezumab Demonstrated Efficacy in Sustained Prevention of Episodic and Chronic Migraine Beginning on Day 1 After Dosing.

Dodick David W DW Gottschalk Christopher C Cady Roger R Hirman Joe J Smith Jeff J Snapinn Steve S

Headache 20201109 10

<h4>Objective</h4>To determine the onset of preventive efficacy with eptinezumab in patients with migraine.<h4>Background</h4>Eptinezumab is a monoclonal antibody inhibiting calcitonin gene-related peptide approved as an intravenously administered treatment for the prevention of migraine.<h4>Methods</h4>Patients who received eptinezumab 100 mg, eptinezumab 300 mg, or placebo in PROMISE7-1 (episodic migraine; 100 mg, n = 221; 300 mg, n = 222; placebo, n = 222) or PROMISE7-2 (chronic migraine; 100 ...[more]

PMID: 33165938

Similar Datasets

Project description:BackgroundPROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment.MethodsPatients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32).ResultsA total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, - 7.7 days; 300 mg, - 8.2 days; placebo, - 5.6 days) was further decreased after an additional dose (100 mg, - 8.2 days; 300 mg, - 8.8 days; placebo, - 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13-24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13-24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events.ConclusionEptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine.Trial registrationClinicalTrials.gov (Identifier: NCT02974153 ). Registered November 23, 2016.

Dataset Information

Eptinezumab Demonstrated Efficacy in Sustained Prevention of Episodic and Chronic Migraine Beginning on Day 1 After Dosing.

Objective

Background

Methods

Results

Conclusions

Publications

Eptinezumab Demonstrated Efficacy in Sustained Prevention of Episodic and Chronic Migraine Beginning on Day 1 After Dosing.

Similar Datasets

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