Aimovig (Erenumab-aooe) First CGRP Receptor Antagonist Approved for the Prevention of Migraine in Adults

March 2019, Vol 12, Tenth Annual Payers' Guide - Select Drug Profiles, Payers' Guide
Lisa A. Raedler, PhD, RPh
Medical Writer
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Migraine is a neurologic disease that affects approximately 37 million people in the United States and comprises several subtypes, including common migraine, complicated migraine, retinal migraine, chronic migraine, and cluster headaches.1,2 Most often diagnosed in women aged 18 to 50 years, migraine has been misunderstood as a less-than-legitimate medical disease.3 However, headache disorders are associated with personal and societal burdens, including pain, disability, poor quality of life, and financial burden.2,4,5 A 2007 study showed that more than 50% of people with frequent migraines require bed rest during their headaches or describe severe impairment of function.4

For patients whose migraine frequency or severity affects daily activities, nonpharmacologic strategies and migraine-preventive medications can be considered.6 However, studies using US claims databases show that 80% to 83% of patients with chronic migraine discontinue oral migraine-preventive medications within 1 year, including antidepressant drugs (ie, amitriptyline), beta-blockers (ie, propranolol), or anticonvulsants (ie, topiramate).6,7

In addition, the US Food and Drug Administration (FDA) approved the use of onabotulinumtoxinA (Botox) for headache prophylaxis in adults with chronic migraine who have headaches 15 days or more monthly, each lasting 4 hours or more.8 Despite the availability of several prevention medications, the unmet needs for people with chronic migraine remain high.

Aimovig Approved for Migraine Prevention

On May 17, 2018, the FDA approved erenumab-aooe (Aimovig; Amgen), an injectable drug that blocks the calcitonin gene–related peptide (CGRP) receptor, for the prevention of migraine in adults.9,10 The effectiveness of erenumab-aooe in preventing migraine was supported by 3 placebo-controlled clinical trials.

“Aimovig provides patients with a novel option for reducing the number of days with migraine. We need new treatments for this painful and often debilitating condition,”9 said Eric Bastings, MD, Deputy Director, Division of Neurology Products, FDA’s Center for Drug Evaluation and Research.

Mechanism of Action

Erenumab-aooe is a human monoclonal antibody that binds to the CGRP receptor and antagonizes CGRP receptor function.10 CGRP is involved in the pathophysiology of migraine through nociceptive mechanisms in the trigeminovascular system.11

Dosing and Administration

The recommended dose of erenumab-aooe is 70 mg given once monthly via subcutaneous injection. Some patients may benefit from a dose of 140 mg given as 2 consecutive subcutaneous injections once monthly.10

A missed dose of erenumab-aooe should be administered as soon as possible. Thereafter, erenumab-aooe can be dosed monthly from the date of the last dose.10

Pivotal Clinical Trials

The efficacy of erenumab-aooe as a preventive treatment of episodic or chronic migraine was assessed in 3 randomized, double-blind, placebo-controlled studies: 2 studies in patients with episodic migraine, defined as 4 to 14 migraine days monthly (ie, STRIVE and ARISE), and one study in patients with chronic migraine, defined as ≥15 headache days monthly, with 8 migraine days or more monthly (Study 3).9,12-14 These studies enrolled patients with a history of migraine, with or without aura, according to the diagnostic criteria of the International Classification of Headache Disorders, 3rd edition.

In the placebo-controlled clinical trials of 2184 patients, 787 patients received at least 1 dose of erenu­mab-aooe 70 mg once monthly, and 507 patients received at least 1 dose of erenumab-aooe 140 mg once monthly during 3 months or 6 months of the double-blind treatment.10 The majority of patients who received erenumab-aooe were female (84%) and white (91%).10 At study entry, patients’ average age was 42 years.10

The STRIVE Clinical Trial

STRIVE was a randomized, multicenter, 6-month, placebo-controlled, double-blind clinical trial of erenu­mab-aooe for the preventive treatment of episodic migraine.10,12 Overall, 955 patients with a history of episodic migraine were randomized to erenumab-aooe 70 mg (N = 317), erenumab-aooe 140 mg (N = 319), or to placebo (N = 319) using subcutaneous injection once monthly for 6 months.10,12 Patients were allowed to use acute headache treatments, including migraine-specific medications (ie, triptans, ergotamine derivatives) and nonsteroidal anti-­inflammatory drugs during the study.10,12

The primary efficacy end point was the change from baseline in the mean monthly migraine days during months 4 to 6. The secondary end points included achievement of a ≥50% reduction from baseline in the mean monthly migraine days during months 4 to 6 (≥50% responders), change from baseline in the mean monthly acute migraine–specific medication days during months 4 to 6, and change from baseline in the mean Migraine Physical Function Impact Diary (MPFID) score during months 4 to 6 (increases in scores indicate worsening).10,12

Overall, 858 (90%) patients completed the 6-month double-blind study.10,12 At baseline, patients’ mean migraine frequency was approximately 8 migraine days monthly.10,12 In this study, both doses of erenumab-aooe demonstrated significant improvements in the key efficacy end points compared with placebo (Table).10,12

Table

Patients who received both doses of erenumab-aooe showed greater reductions from baseline in the mean monthly MPFID everyday activity scores averaged during months 4 to 6 (P <.001 for both cohorts).10,12

The ARISE Clinical Trial

ARISE, the second phase 3 clinical trial of erenu­mab-aooe in patients with episodic migraines, randomized 577 patients to receive the injectable drug given at a dose of 70 mg (N = 286) or placebo (N = 291).10,13 During 3 months, patients who received erenumab-aooe had 1.0 fewer monthly migraine days versus those receiving placebo (P <.001).10,13 Overall, 40% of those who received erenumab-aooe had a ≥50% reduction in monthly migraine days compared with 30% of placebo recipients (P = .010).10,13

Study 3

Study 3 was a phase 2, randomized, double-blind, placebo-controlled study that compared erenumab­aooe with placebo in 667 patients with a history of chronic migraine with or without aura.10,14 During the course of 3 months, patients who received 70 mg or 140 mg of erenumab-aooe had fewer monthly migraine days compared with patients who received placebo.10,14 Both doses of erenumab-aooe resulted in −6.6 days compared with −4.2 days with placebo, a difference of −2.5 days (95% confidence interval, −3.5 to −1.4; P <.0001).10,14

Adverse Events

In the 3 key clinical trials, the most common (incidence of ≥3% and more frequent than with placebo) adverse reactions associated with erenumab-aooe therapy were injection-site reactions (6% and 5% in patients who received erenumab-aooe 70 mg and 140 mg, respectively) and constipation (1% and 3% in patients who received erenumab-aooe 70 mg and 140 mg, respectively).10

Erenumab-aooe has no contraindications.10

Use in Specific Populations

There are no adequate data regarding the risk to the fetus associated with erenumab-aooe use in pregnant women, the presence of erenumab-aooe in human milk, the effects on breastfed infants, or the effects on milk production.10

The safety and effectiveness of erenumab-aooe have not been established in children.10

Clinical studies of erenumab-aooe did not include sufficient numbers of patients aged ≥65 years to learn whether older patients respond differently to erenumab-aooe from younger patients.10

Warnings and Precautions

The prescribing information for erenumab-aooe has no warnings or precautions.10

Conclusion

The approval of erenumab-aooe offers patients a new option in reducing the number of days with migraine, a painful and debilitating condition. Randomized clinical trials have demonstrated that erenumab-aooe, the first FDA-approved once-monthly self-injectable drug that inhibits the CGRP receptor, which is involved in the pathophysiology of migraine, is more effective than placebo in preventing migraines in adults with episodic or chronic migraine. The safety profile of erenumab is similar to that of placebo.

References

  1. American Migraine Foundation. What type of headache do you have? May 9, 2017. https://americanmigrainefoundation.org/understanding-migraine/what-­type-of-headache-do-you-have/. Accessed September 21, 2018.
  2. American Migraine Foundation. What is migraine? https://americanmigrainefoundation.org/living-with-migraine/. Accessed December 19, 2018.
  3. American Migraine Foundation. The impact of migraine: Q&A with Dr. David Dodick. April 20, 2017. https://americanmigrainefoundation.org/understanding-migraine/impact-of-migraine-qa-dr-david-dodick/. Accessed September 21, 2018.
  4. Lipton RB, Bigal ME, Diamond M, et al; for the AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343-349.
  5. World Health Organization. Headache disorders. April 8, 2016. www.who.int/mediacentre/factsheets/fs277/en/. Accessed September 17, 2017.
  6. WebMD. Medicines that can prevent migraine headaches. www.webmd.com/migraines-headaches/preventive-migraine-medicine#2. Accessed September 21, 2018.
  7. Hepp Z, Dodick DW, Varon SF, et al. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35:478-488.
  8. Jeffrey S. Botox approved for headache prophylaxis in chronic migraine. Medscape Medical News. October 16, 2010. www.medscape.com/viewarticle/730682. Accessed September 21, 2018.
  9. US Food and Drug Administration. FDA approves novel preventive treatment for migraine. May 17, 2018. www.fda.gov/newsevents/newsroom/pressannouncements/ucm608120.htm. Accessed September 21, 2018.
  10. Aimovig (erenumab-aooe) injection, for subcutaneous use [prescribing information]. Cambridge, MA: Amgen; May 2018.
  11. Lassen LH, Haderslev PA, Jacobsen VB, et al. CGRP may play a causative role in migraine. Cephalalgia. 2002;22:54-61.
  12. Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377:2123-2132.
  13. Dodick DW, Ashina M, Brandes JL, et al. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38:1026-1037.
  14. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo­controlled phase 2 trial. Lancet Neurol. 2017;16:425-434.
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