FDA Updates Erenumab Label to Include Hypersensitivity Risk
After almost a year on the market, post-marketing data has been suggestive of a risk of anaphylaxis and angioedema in patients who are hypersensitive to erenumab or the excipients.
The FDA has added a safety-related label change to erenumab (Aimovig, Amgen/Novartis) to include a contraindication for patients with serious hypersensitivity to erenumab or to any of the excipients due to the risk of anaphylaxis and angioedema.1
The FDA label update noted that hypersensitivity reactions, “including rash, angioedema, and anaphylaxis,” have been reported with the anti-calcitonin gene-related peptide (CGRP) treatment in its post-market time. It was originally approved by the agency in May 2018.
“Most hypersensitivity reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration. If a serious or severe hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy,” the agency wrote. It did note in the label update that because the reactions were voluntarily reported from a population of indeterminant size, it is not necessarily possible to estimate their frequency or establish a causal relationship to drug exposure.
In its development, erenumab was evaluated in 3 different clinical studies, 2 studies in patients with episodic migraine and 1 study in patients with chronic migraine. In the first study (NCT02456740) evaluating patients with episodic migraine, erenumab 70 mg and 140 mg had significantly lower mean monthly migraine days (3-4 migraine day difference from baseline), increased the proportion of patients with a ≥50% reduction from baseline in mean monthly migraine days (43.3% to 50% responders in erenumab), lowered monthly acute migraine-specific medication days (1-2 day difference from baseline), and saw improvements in migraine physical function impact diary (MPFID), a measurement of the impacts that migraine has on everyday activities and physical impairment.2
Similarly, in the second study (NCT02483585) conducted on patients with episodic migraine, erenumab 70 mg was shown to significantly lower monthly migraine days, increased the proportion of patients with ≥50% reduction from baseline in mean monthly migraine days, and lowered monthly acute migraine-specific medication days. MFPID improvements in scores of at least a 5-point reduction, as a predetermined outcome, was not achieved by erenumab compared to placebo.3
The third study (NCT02066415) on erenumab efficacy was assessed in patients with chronic migraine. erenumab 70 mg and 140 mg had significantly lower mean monthly migraine days (6.6 migraine day difference from baseline), increased proportion of patients with ≥50% reduction from baseline in mean monthly migraine days (39.9% to 41.2% responders in erenumab), and lower monthly acute migraine-specific medication days (approximately 4-day difference from baseline).4
Erenumab was joined by fremanezumab (Ajovy, Teva) and galcanezumab (Emgality, Eli Lilly) in September 2018. All are priced at $575 per dose, which equates to $6900 per year. One more therapy, eptinezumab, is expected to reach the FDA in 2019. At the 2018 American Neurological Association Annual Meeting, Andrew C. Charles, MD, from the University of California, Los Angeles, noted that many of the manufacturers are offering free trials of the drugs that range from 2 months to a year. Moreover, he added, most insurance companies are approving treatment with preauthorization, with a copay between $25 and $50.
In terms of administration, Stephen Silberstein, MD, of Jefferson University, said on a NeurologyLiveâ Peer Exchange panel that “fremanezumab can be given monthly or in a triple dose quarterly as a patient option. Erenumab is available as a monthly dosage formulation. Galcanezumab is available monthly. And last but not least, when eptinezumab comes in the market, it’s going to be available as an intravenous formulation, which should be given every 3 months.”
“We don’t know yet in practice, and correct me if I’m wrong, which is the best approach, and it may be individualized. We have options of drugs with different mechanisms of action, with different groups of administration and with different frequency of administration,” Silberstein added.
1. Aimovig [FDA label update]. Updated March 11, 2019. accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=1894. Accessed March 13, 2019.
2. 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. doi: 10.1056/NEJMoa1705848.
3. Dodick DW, Ashina M, Brandes JL, et al. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026-1037. doi: 10.1177/0333102418759786.
4. 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(6):425-434. doi: 10.1016/S1474-4422(17)30083-2.