News & Perspective

Novel FDA approval on calcitonin gene-related peptide receptor antagonist as migraine preventive treatment

Neurology
3 months ago, OP Editor

Erenumab-aooe, being able to reduce the frequency of migraine , was approved by the US Food and Drug Administration (FDA) as a preventive treatment on migraine in adults.1,2 It is the first calcitonin gene-related peptide (CGRP) receptor antagonist approved by FDA for the preventive migraine treatment.2 The results of the phase 3b trial showing efficacy and safety of erenumab on patients with episodic migraine who have failed prior preventive migraine treatment were presented at the 2018 American Academy of Neurology (AAN) 70th Annual Meeting.3

The primary goal of migraine prophylactic treatment is to lower the frequency, severity, and length of the attacks.4 Currently, prophylactic treatment can alleviate the problem faced by patients with chronic migraine with beta-blockers as one of the commonly prescribed migraine prophylactic treatment.4,5 However, relapse and behavioral adverse events (AEs) including drowsiness, lethargy, sleep disorders, and depression are difficulties encountered during migraine management due to the low specificity of these drugs.6

Erenumab-aooe is an antagonist of CGRP receptor which plays an important role in migraine pathophysiology.7 As previous studies have shown that exogenous CGRP can induce acute headache similar to migraine, CGRP receptor antagonist may block the action of CGRP and thus be used as a preventive treatment of migraine.8,9

“[Erenumab] provides patients with a novel option for reducing the number of days with migraine,” said Dr. Eric Bastings, deputy director of the Division of Neurology Products in the FDA’s center for Drug Evaluation and Research. “We need new treatments for this painful and often debilitating condition.”2

Previously, two phase 3 studies of erenumab, STRIVE and ARISE, have demonstrated the efficacy and safety of erenumab in patients with chronic and episodic migraine.1,7 The number of monthly migraine days (MMDs) in erenumab group was reduced to a larger extent, as compared with placebo group.1,7 In ARISE, ≥50% reduction in MMDs was achieved by 39.7% in erenumab group and 29.5% in placebo group (OR=1.59; 95% CI: 1.12 to 2.27; p=0.01).7 The number of migraine-specific medication treatment days (MSMDs) were reduced by -1.2 days in erenumab group and -0.6 days in placebo groups, corresponding to a treatment difference of -0.6 (95% CI: -0.2 to -1.0; p=0.002).7 Similar results are shown in STRIVE.1

The results of a new phase 3b trial LIBERTY, a 12-week, double-blind, randomized study, was presented at the 2018 AAN meeting.3,10 The study enrolled 246 patients with episodic migraine who have failed 2-4 prior preventive migraine treatments, and randomized them to receive wither 140mg erenumab or placebo for 12 weeks.3,10 They experienced an average of nine migraine headaches a month and used an acute migraine drug to stop attack five times a month.3,10 At baseline, 38.6%, 37.8%, and 22.8% had been treated unsuccessfully with 2,3 and 4 prior preventive migraine treatments respectively. At week 12, the proportion of patients achieving ≥ 50% reduction in MMDs was 2.73 times higher in those receiving erenumab as compared to placebo (30.3% vs 13.7%; OR=2.73; 95% CI: 1.43,5.19; p=0.002).3,10 Moreover, greater reductions in MMDs and MSMDs were also demonstrated in the erenumab group.3,10 The mean difference against placebo was -1.61 (95% CI: -0.52 to -2.70) and -1.73 (95% CI: -1.01 to -2.46) for MMDs and MSMDs, respectively.3,10

The rates of AEs were similar between erenumab and placebo group, and none of the participants discontinued due to AEs.3,10 Most common AEs reported in the clinical trials were injection site reactions and constipation.2

Although the study period of LIBERTY was relatively short, Dr. Uwe Reuter, the Charite University Medicine Berlin, Germany, noted that erenumab is a ‘game changer’.11 “This is the first time that you have a specific receptor-targeted drug in migraine prevention.” he said. “Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief. More research is now needed to understand who is most likely to benefit from this new treatment.” 10

 

  1. Goadsby PJ, Reuter U, Hallström Y, et al. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017;377(22):2123-2132.
  2. FDA approves novel preventive treatment for migraine. FDA News Release. 2018 (Accessed May 28 2018, at
    https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm608120.htm).
  3. Reuter U, Goadsby P, Lanteri-Minet M, et al. Efficacy and safety of erenumab in patients with episodic migraine who have failed 2-4 prior preventive migraine treatments (PMTs). American Academy of Neurology 70th Annual Meeting. April 17, 2018; Los Angeles, US.
  4. May A. Hints on Diagnosing and Treating Headache. Dtsch Arztebl int. 2018;115(17):299-308.
  5. Diener Hch. Pharmacological approaches to migraine. J Neural Transm Suppl. 2003; (64):35-63.
  6. Silberstein SD. Preventive Migraine Treatment. Continuum (Minneap Minn). 2015;21(4 Headache):973-89.
  7. Dodick DW, Ashina M, Brandes JL et al. Arise: A Phase 3 Randomised Trial of Erenumab for Episodic Migraine. Cephalalgia. 2018;38(6): 1026-1037.
  8. Edvinsson L. The CGRP Pathway in Migraine as a Viable target for Therapies. Headache. 2018;58 Suppl 1:33-47.
  9. Hansen JM, Hauge AW, Olesen J, et al. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migrane with aura. Cephalalgia. 2010;30(10):1179-86.
  10. WHEN OTHERS FAIL, NEW MIGRAINE TREATMENT MAY WORK. American Academy of Neurology Press Room. 2018 (Accessed May 29, 2018, at https://www.aan.com/PressRoom/Home/PressRelease/1641).
  11. Anderson P. Erenumab Prevents Episodic Migraine in Refractory Patients. Medscape Medical News. 2018 (Accessed May 29, 2018, at https://www.medscape.com/viewarticle/895446#vp_1).

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