The anti-calcitonin gene-related peptide monoclonal antibody fremanezumab has been shown to reduce migraines compared to placebo, however experts say data is still needed on the long-term safety of the drug class.
The phase III randomised trial involved 875 adults with episodic migraine, in whom multiple medication classes had not previously failed.
From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group, reported David Dodick, MD, from the Mayo Clinic in Phoenix, and colleagues.
This resulted in a difference with monthly dosing vs placebo of –1.5 days (95% CI, –2.01 to –0.93 days; P < .001) and with single higher dosing vs placebo of –1.3 days (95% CI, –1.79 to –0.72 days; P < .001), they reported in JAMA.
The most common adverse events that led to discontinuation were injection site erythema, injection site induration, diarrhea, anxiety and depression.
“Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy,” the researchers concluded.
Writing in a linked editorial Dr Elizabeth W. Loder from the Brigham and Women’s Hospital, Harvard Medical School, Boston, and Matthew S, Robbins from the Jack D. Weiler Hospital at the Montefiore Headache Center, Albert Einstein College of Medicine in New York said an important apparent benefit of fremanezumab and other 3 CGRP monoclonal antibodies in development is their low burden of ‘common nuisance adverse events’.
However, they noted that the long-term safety of the drug class remained unknown. Some concerns around their safety were based on the known actions of CGRP, but off-target or unsuspected safety problems also could emerge, they said.
“…there have been 3 deaths in clinical trial participants who received CGRP monoclonal antibodies. In the trial reported by Dodick and colleagues, the death that occurred was a suicide 109 days after the patient received 675 mg of fremanezumab. ”
While the deaths may not have been treatment related they were ‘noteworthy’ as clinical trials usually aimed to enroll participants with migraine who are otherwise healthy.
“The FDA undoubtedly will scrutinize the deaths and adverse events reported in the trials of fremanezumab and other CGRP monoclonal antibodies. If the result is restrictive labeling, it could greatly limit the patient population for these drugs, which are in any case likely to prove costly and challenging for patients to access,” they said.
They also noted that as the study excluded potential participants with previous failure of as few as 2 preventive medication classes for migraine the results may not necessarily apply to patients with severe, treatment-resistant migraine, who were the patients most likely to be prescribed and have access to these treatments in clinical practice.
The study was funded by TEVA pharmaceuticals.