Migraine FDA Watch


FDA Approves Galcanezumab as Preventive Therapy for Episodic or Chronic Migraine

On September 27, 2018, the U.S. Food and Drug Administration (FDA) approved galcanezumab for the preventive treatment of migraine in adults. Galcanezumab, a calcitonin gene-related peptide (CGRP) receptor antagonist, is a once-monthly, self-administered 120 mg subcutaneous injection. The FDA approval was based on data from phase 3 trials involving patients with episodic or chronic migraine.

The EVOLVE-1 and EVOLVE-2 clinical trials were 6-month, double-blind, placebo-controlled studies that enrolled adult patients with episodic migraine, which was defined as 4 to 14 migraine headache days (MHDs) per month. In EVOLVE-1, 62% of episodic migraine patients receiving galcanezumab experienced at least a 50% reduction in MHDs in any given month, on average, compared with a 39% rate seen in placebo recipients. In addition, 39% of patients randomized to the galcanezumab arm achieved at least a 75% reduction in MHDs in any given month, compared with 19% for placebo-treated patients. Approximately 16% of patients in EVOLVE-1 achieved a 100% reduction in MHDs in any given month, on average, compared with 6% for placebo patients. Similar improvements were observed in EVOLVE-2 with regard to experiencing at least a 50% reduction in MHDs in any given month. In both trials, the mean decrease in migraine headache days from baseline were significantly better than what was observed in placebo-treated individuals.

The REGAIN trial was a 3-month, double-blind, placebo-controlled study that enrolled adult patients with chronic migraine, which was defined as at least 15 headache days per month with at least 8 MHDs per month. In REGAIN, 28% of chronic migraine patients receiving galcanezumab experienced at least a 50% reduction in MHDs in any given month, on average, compared with a 15% rate seen in placebo recipients. In addition, the average decrease in migraine headache days from baseline were significantly better than what was seen in placebo-treated individuals.

The safety of galcanezumab was evaluated in three clinical trials that included more than 2,500 patients. Hypersensitivity reactions (e.g., rash, urticaria, and dyspnea) were reported with galcanezumab in clinical studies, can occur days after administration, and may be prolonged. The most common adverse reactions (incidence ≥2% for galcanezumab and at least 2% greater than placebo) were injection site reactions (18% vs 13%).

The recommended dose for galcanezumab is 240 mg, administered in 2 consecutive subcutaneous injections of 120 mg each. Galcanezumab is contraindicated in patients with serious hypersensitivity to the active agent or to any of the excipients.

FDA Announcement

Prescribing Information

References:

  1. Eli Lilly and Company [press release]. Lilly’s Emgality™ (galcanezumab-gnlm) receives U.S. FDA approval for the preventive treatment of migraine in adults. September 27, 2018. Available at: https://investor.lilly.com/node/39641/pdf. Accessed October 2, 2018.
Back to top of page

FDA Approves Fremanezumab as Quarterly or Monthly Migraine Prevention Therapy

On September 14, 2018, the U.S. Food and Drug Administration (FDA) approved fremanezumab, a self-administered injectable calcitonin gene-related peptide (CGRP) receptor antagonist, for the preventive treatment of migraine in adults. The manufacturer notes that fremanezumab is the only anti-CGRP treatment indicated for the prevention of migraine available in quarterly (675 mg) and monthly (225 mg) dosing options.

Data from two phase 3, placebo-controlled clinical trials involving adult patients with disabling migraine were the basis of the FDA’s approval. In these studies, fremanezumab was studied as both a stand-alone preventive treatment and in combination with oral preventive therapies.

In the first study, more than 1,000 patients with chronic migraine (CM) were enrolled in the HALO-CM trial. Those randomly assigned to receive 675 mg of fremanezumab for 1 month followed by 225-mg dose treatments for the following 2 months (monthly dosing) or placebo for the next 2 months (quarterly dosing) had a significantly fewer monthly headache days (4.6 and 4.3 days, respectively) when compared with those receiving only three placebo injections per month (2.5 days).

In the second study, 873 patients with episodic migraine (EM) were enrolled in the HALO-EM trial. The monthly and quarterly fremanezumab dosing groups each met the study’s primary endpoint of greater reduction in monthly migraine days at 12 weeks when compared with the placebo group (3.7 and 3.4 days, respectively, vs 2.2 days).

Fremanezumab is contraindicated in patients with serious hypersensitivity to the active ingredient or to any of the excipients. Hypersensitivity reactions, including rash, pruritis, drug hypersensitivity, and urticaria were reported with fremanezumab in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to 1 month after administration. The most common adverse reactions (occurring in ≥5% of cases and greater than placebo) were injection site reactions and infections.

FDA Announcement

Prescribing Information

References:

Teva Pharmaceutical Industries Ltd [press release]. Teva announces U.S. approval of AJOVY™ (fremanezumab-vfrm) injection, the first and only anti-CGRP treatment with both quarterly and monthly dosing for the preventive treatment of migraine in adults. September 14, 2018. Available at: https://www.tevapharm.com/news/teva_announces_u_s_approval_of_ajovytm_fremanezumab_vfrm_injection_the_first_and_only_
anti_cgrp_treatment_with_both_quarterly_and_monthly_dosing_for_the_preventive_treatment_of_migraine_in_adults_09_18.aspx
. Accessed October 2, 2018.

Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377:2113-2122. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1709038. Accessed October 2, 2018.

Dodick DW, Silberstein SD, Bigal ME, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA. 2018;319:1999-2008. Available at: https://jamanetwork.com/journals/jama/fullarticle/2681193. Accessed October 2, 2018.

Back to top of page

FDA Approves Erenumab for Migraine Prevention

On May 17, 2018, the U.S. Food and Drug Administration (FDA) approved erenumab for the preventive treatment of migraine in adults. The novel therapy was the first calcitonin gene-related peptide receptor (CGRP) receptor antagonist to be approved by the FDA. Erenumab 70 mg is self-administered once a month using the manufacturer’s proprietary autoinjector and does not require a loading dose. Some patients may benefit from a dosage of 140 mg once monthly.

The effectiveness of erenumab for the preventive treatment of migraine was evaluated in 3 clinical trials. The first included 955 participants with a history of episodic migraine and found that, over the course of 6 months, patients treated with erenumab experienced, on average, 1 to 2 fewer monthly migraine days than those on placebo. A second study included 577 similar patients who were treated for 3 months and demonstrated that those receiving the drug experienced, on average, 1 fewer migraine day per month than those on placebo. A third trial evaluated 667 patients with a history of chronic migraine and showed that, over 3 months of therapy, patients treated with erenumab experienced, on average, 2.5 fewer monthly migraine days than those receiving placebo.

The LIBERTY trial, a dedicated phase 3b study, was conducted in difficult-to-treat populations, which was defined as those with episodic migraine who had failed 2 to 4 prior treatments. This trial showed that patients taking erenumab had a nearly 3-fold higher likelihood of having their migraine days cut by half or more when compared with placebo.

The efficacy, tolerability, and safety of erenumab was assessed in more than 3,000 patients, including LIBERTY and an ongoing open-label extension of up to 5 years in duration. In these clinical studies, the most common adverse reactions were injection site reactions and constipation.

FDA Announcement

Prescribing Information

References:

Amgen [press release]. FDA approves Aimovig™ (erenumab-aooe), a novel treatment developed specifically for migraine prevention. May 17, 2018. Available at: https://www.amgen.com/media/news-releases/2018/05/fda-approves-aimovig-erenumabaooe-a-novel-treatment-developed-specifically-for-migraine-prevention/. Accessed October 2, 2018.

Ashina M, Tepper S, Brandes JL, et al. Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia. 2018;38:1611-1621. Available at: http://journals.sagepub.com/doi/abs/10.1177/0333102418788347. Accessed October 2, 2018.

Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425-434. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(17)30083-2. Accessed October 2, 2018.

ClinicalTrials.gov. A study evaluating the effectiveness of AMG 334 injection in preventing migraines in adults having failed other therapies (LIBERTY). NLM Identifier: NCT03096834. September 10, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT03096834. Accessed October 2, 2018.


Back to top of page