Fremanezumab for the prevention of chronic migraine

Fremanezumab (TEV-48125) is a humanized IgG2a monoclonal antibody that selectively and potently binds to calcitonin gene–related peptide (CGRP) - a 37–amino acid neuropeptide involved in central and peripheral pathophysiological events of migraine

• fremanezumab targets both alpha and beta isoforms of the CGRP ligand (not the receptor), has flexible dosing, and is administered by means of subcutaneous injection
• study evidence noted (1):
  • Fremanezumab was associated with a higher incidence of injection-site reactions than placebo, but the severity of such reactions did not differ significantly among the trial groups.
  • Fremanezumab, a monoclonal antibody, is not metabolized in the liver and is eliminated through catabolism to smaller peptides or amino acids - mild transient elevations in liver enzyme levels occurred, and the levels reverted to normal without discontinuation of the trial regimen. All the patients who had these elevations used concomitant medications with a potential to cause increases in liver enzyme levels
  • endogenous CGRP is a vasodilator, but there were no hemodynamic changes with fremanezumab

NICE have stated that (2):

• Fremanezumab is recommended as an option for preventing migraine in adults, only if:
  • they have 4 or more migraine days a month
  • at least 3 preventive drug treatments have failed and
  • the company provides it according to the commercial arrangement
• Stop fremanezumab after 12 weeks of treatment if:
  • in episodic migraine (fewer than 15 headache days a month), the frequency does not reduce by at least 50%
  • in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine), the frequency does not reduce by at least 30%
    
    
• the NICE committee state:
  • treatments for preventing chronic or episodic migraine include beta-blockers, antidepressants and anticonvulsant drugs
    • if chronic migraine does not respond to at least 3 preventive drug treatments, botulinum toxin type A or best supportive care (treatment for the migraine symptoms) is offered
    • if episodic migraine does not respond to at least 3 preventive drug treatments, best supportive care is offered
  • for people whose migraine has not responded to at least 3 oral preventive treatments, clinical trial evidence shows that fremanezumab works better than best supportive care in both episodic and chronic migraine. However, it is unclear if fremanezumab works better than botulinum toxin type A

Reference:

• Silberstein SD et al. Fremanezumab for the Preventive Treatment of Chronic Migraine. NEJM 2017 Nov 30;377(22):2113-2122
• NICE (February 2022). Fremanezumab for preventing migraine