FDA Approves Fremanezumab for Migraine Prevention


The monoclonal antibody is now the second member of the CGRP inhibitor class to be approved by the FDA.

Dr Peter Goadsby

Peter Goadsby, MD, PhD, DSc, a professor of neurology at both the University of California San Francisco and Kings College London

Peter Goadsby, MD, PhD, DSc

The FDA has approved the use of fremanezumab-vfrm (Ajovy, Teva Pharmaceuticals) for the prevention of migraine in adults, according to a statement from Teva Pharmaceutical, the developer of the calcitonin gene-related peptide (CGRP) inhibitor.1

The approval was based on the supporting data from 2 studies in the phase III HALO clinical trial program. In the trials, the fully humanized anti-CGRP monoclonal antibody fremanezumab reduced monthly migraine days by ≥50% in roughly 45% of patients with episodic migraine and about 40% of patients with chronic migraine in clinical trials.

Fremanezumab follows erenumab-aooe (Aimovig, Amgen/Novartis) as the second approved member of this new class of medications.

“The future of the prevention of migraine is very bright,” Peter Goadsby, MD, PhD, DSc, a professor of neurology at both the University of California San Francisco and King’s College London, told NeurologyLive. “We have these new medicines, and we're going to have others as we understand the pathways. I think there will be synergies. There may be synergies between the CGRP pathway and perhaps the pituitary adenylate cyclase activating polypeptide pathway, and there may be synergies between the ditans and the CGRP monoclonals, the gepants and the monoclonals—we've much to learn.”

In the first pivotal study,2 the therapy was assessed in both quarterly and monthly regimens in chronic migraine. This study revealed that the average number of headache days per month was reduced by 4.3 ±0.3 for those taking fremanezumab quarterly (n = 376) and 4.6 ±0.3 for those taking fremanezumab monthly (n = 379), compared with 2.5 ±0.3 with placebo (n = 375; P <.001 for both). Meanwhile, 38% of those on the quarterly regimen and 41% of those on the monthly regimen achieved ≥50% reduction in monthly migraine days, compared to 18% of those given placebo (P <.0001 for both).

Additionally, the degree of headache-related disability as measured by the 6-item Headache Impact Test (HIT-6) decreased, with significantly greater reductions in HIT-6 scores with fremanezumab quarterly (6.4 ±0.5 points) and fremanezumab monthly (6.8 ±0.4 points) than with placebo (4.5 ±0.5 points; P <.001 for both).

In the second trial, which assessed fremanezumab for episodic migraine,3 the mean number of monthly migraine days for those receiving the treatment monthly was 4.9 days (n = 290; least-squares mean [LSM], -3.7 days) and 5.3 days for those receiving the therapy in a single, higher dose (n = 291; LSM, -3.4 days). In comparison, those administered placebo saw 6.5 monthly migraine days (LSM, -2.2 days). The differences of -1.5 days (95% CI, -2.01 to -.093) for the monthly group and -1.3 days (95% CI, -1.79 to -0.72) for the single, higher dose group were statistically significant (P <.001 for both).3

“What excites me about this class is that, for those who do respond, it’s very likely that the tolerability profile is such that they’re able to stay on the medication and they’re able to tolerate it and they might not have any adverse effects,” David Dodick, MD, the lead investigator of the episodic trial, told NeurologyLive. “The longer they stay on it, if you look at the 1-year, open-label data for those that are staying on it, efficacy rates climb over time. The longer you’re able to adhere to a treatment that’s working for you, the better the patient outcome is over time. That’s the real difference here.”

The most common adverse events in both trials were injection site reactions of pain, induration, and erythema. All told, 22 of the 1238 total patients (0.01%) treated with the CGRP inhibitor across both trials discontinued treatment.

“The burden of illness faced by those with migraine is immense and can negatively impact every facet of their lives underscoring a significant unmet need for new preventive treatment options,” Stephen D. Silberstein, MD, the lead author and principal investigator of the HALO trial, and a professor of neurology and the director of the Jefferson Headache Center at Thomas Jefferson University Hospital, said at the time of HALO’s publication.2

The therapy is currently being investigated for its potential as a treatment for cluster headache in the phase III ENFORCE trial (NCT03107052), which is set to conclude next year. The FDA has granted it a Fast Track designation for this indication. Additionally, Teva has announced it is conducting a phase II trial of fremanezumab in post-traumatic headache as well.

The wholesale cost for the monoclonal antibody will be $575 for the monthly dose and $1,725 for the quarterly dose, which is the same price announced for erenumab. Teva noted that out of pocket costs would vary based on insurance providers but could be as low as $0 per month for some patients.

“Migraine is a disabling neurological disease that affects more than 36 million people in the United States,” Stephen Silberstein, MD, director, Jefferson Headache Center at Thomas Jefferson University Hospital, said in a statement. “About 40% of people living with migraine may be appropriate candidates for preventive treatment, yet the majority of them are untreated. I am pleased to have another treatment option that may allow my patients to experience fewer monthly migraine days.”


1. 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 [press release]. Jerusalem: Teva Pharmaceutical Industries Ltd; Published September 2018. https://www.businesswire.com/news/home/20180914005613/en/Teva-Announces-U.S.-Approval-AJOVYTM-fremanezumab-vfrm-Injection. Accessed September 2018.

2. Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic

migraine. N Engl J Med. 2017;377:2113-2122.



3. Dodick DW,


SD, Bigal ME, et al. Effect of


compared with placebo for prevention of


migraine: a randomized clinical trial. JAMA. 2018;319(19):1999-2008.



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