The monoclonal antibody reportedly reduced headache days by 4.3 and 4.6 days for the 625 mg and 225 mg doses, respectively.
Stephen Silberstein, MD
The use of fremanezumab for the preventive treatment of chronic migraine has been shown to reduce the frequency of headaches when compared with placebo, according to new data published in the New England Journal of Medicine.
A monoclonal antibody that targets calcitonin gene-related peptide (CGRP), the drug was compared to placebo in both 225-mg and 675-mg doses, to be administered subcutaneously to a patient population of 1130. The trial was led by Stephen D. Silberstein, MD, the director of the Headache Center at Jefferson University Hospital and a professor of neurology.
The results showed a least squares mean (±SE) reduction in the average headache days experienced per month by 4.3 ±0.3 for the 675-mg dose, while the 225 mg dose revealed a reduction of 4.6 ±0.3 headache days (P <.0001). The placebo group experienced a 2.5 ±0.3 reduction in headache days, almost half of that of quarterly and monthly groups.
“CGRP treatments work both acutely and preventatively for the treatment of migraine, and there is a lot of evidence that CGRP is involved in sensory neural transmission, so it lives in the brain, and the structures we would think would be involved with migraine,” Richard Lipton, MD, the director of the Montefiore headache center and the Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, told MD Magazine.
Lipton noted that there has been a “staggering record of success” in regards to the monoclonal antibody class of medicines. “Targeting CGRP or its receptor is clearly an effective strategy for treating migraine,” he said.
In the 12-week trial period, patients were randomized 1:1:1 to 3 groups - quarterly, monthly, and placebo. The quarterly group received a single dose of 675-mg fremanezumab at baseline followed by placebo at weeks 4 and 8 (n = 376), the monthly group received a 675-mg dose of fremanezumab at baseline followed by a 225-mg dose at weeks 4 and 8 (n = 379), and the placebo group received a matching placebo administered at baseline, week 4, and week 8 (n = 375).
At baseline, the quarterly group reported a mean of 13.2 headache days, the monthly group reported a mean of 12.8 days, and the placebo group reported a mean of 13.3 days. A ≥50% reduction in the number of headache days was reported by 38% of the quarterly group and 41% in the monthly group, compared to 18% in the placebo group (P <.001).
“We used to say the goal of preventive therapy was to reduce treatment by 50% or more. If we get a 50% reduction, that’s huge,” Lipton said. “If somebody is having 10 headaches a month, they get 5 days back. If they’re having 20 headache days a month, they get 10 days a month back. That is a big deal.”
In terms of safety, 5 patients in each of the fremanezumab groups reported abnormal hepatic function (1%), and 3 patients reported the same in the placebo group (<1%). The safety profiles of monoclonal antibodies, like fremanezumab, has been a topic to get excited about, Lipton said.
“The other thing that is exciting about this class of medicines is that most of the drugs we use for migraine prevention act on the brain, and we use drugs that were developed for epilepsy like topiramate or divalproex sodium, which have a lot of side effects,” Lipton said. “Monoclonal antibodies have a relatively favorable side effect profile.”
The drug was previously tested for outcomes in both chronic and episodic migraine in the HALO trial, showing positive results there as well. At the time, Marcelo Bigal, MD, PhD, chief medical officer & head of specialty clinical development at Teva Pharmaceuticals, the product's developer, told MD Magazine: “If you have chronic migraine, you want to bring them down to episodic, and once they are episodic, the goal is to get you to a lower frequency and prevent them from becoming chronic again. The results, by default, need to be seen together. Having the full gamut [to treat both] is what is important about this treatment.”