Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy–2) study

Abstract

Background PROMISE-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. Methods Patients 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). Results A 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. Conclusion Eptinezumab 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 registration ClinicalTrials.gov (Identifier: NCT02974153). Registered November 23, 2016.

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“…Most of these agents target the CGRP peptide, except erenumab, which targets the CGRP receptor. All these treatments have led to significant reductions from baseline in either episodic [ 119 , 120 , 121 , 122 ] and/or chronic [ 123 , 124 , 125 , 126 ] monthly migraine or headache days vs. placebo. A variety of secondary endpoints were also achieved in the clinic trials, such as reduction in acute medication and several impact and disability measures [ 110 ].…”

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

“…The mean frequency at baseline was approximately 16.1 migraine days/month. The study results demonstrated that the mean reduction in migraine days from baseline to placebo was −7.7 days for 100 mg, −8.2 days for 300 mg, and −5.6 days for placebo [ 84 , 85 ].…”

“…Patients treated with eptinezumab or placebo, presented no clinically significant differences in vital signs, 12-lead ECGs, or laboratory safety data. Likewise, the most commonly reported AEs for eptinezumab, at an incidence of ≥2%, were hypersensitivity reactions (hypersensitivity, urticaria, flushing/hot flush, rash, and pruritus), nasopharyngitis (6.3%), upper respiratory infection (4%), nausea (3.4%), arthralgia (2.3%), urinary tract infection (3.1%), dizziness (2.6%), fatigue (2%) and anxiety (2%) [ 84 , 85 , 88 ].…”

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“…In terms of responder rates, 27% and 33% of 100 mg and 300 mg groups respectively had ≥75% responder rates vs 15% for the placebo group. These benefits were sustained till the end of the 24 week treatment period with no new side effects [20]. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients [20].…”