CGRP mAbs will offer new opportunities for migraine prophylaxis


By Michael Woodhead

28 May 2019

Dr Bronwyn Jenkins

Migraine prophylaxis is likely to be improved by a new wave of monoclonal antibody-based treatments that act on calcitonin gene related peptide (CGRP), according to a ‘headache update’ presentation at ANZAN 2019.

Dr Bronwyn Jenkins, a consultant neurologist in Sydney with a special interest in headache, said it had taken more than 30 years since the discovery of CGRP in 1982 to have the first anti-migraine prophylactics ready for clinical use.

Early research had shown that CGRP levels were increased in migraine, including in the trigeminalcervical nucleus. CGRP infusion triggered migraine and that sumatriptan  normalised CGRP levels.

In more recent times, three CGRP-targeted monoclonal antibody agents had been developed: erenumab against the CGRP receptor and fremanezumab and galcanezumab which act against the CGRP neurotransmitter itself.

The three agents are usually given subcutaneously on a monthly basis, and in randomised controlled trials they had shown significant preventive effects against chronic migraine. With erenumab, for example, the proportion of patients showing more than a 50% response rate in chronic migraine was double that of placebo, Dr Jenkins noted.

All phase II and III trials had shown positive effects in episodic and chronic migraine, with the drugs being well tolerated and having no known interactions. However, while the drugs had shown safety in around 10,000 patients in short term trials, there was still limited data beyond three years of use, she cautioned.

And since they had a quicker onset (3 months vs 6 months) compared to previous prophylactics and because monoclonal antibodies did not cross the blood brain barrier, the development of CGRP-targeted therapies had prompted a re-think on the brain pathways leading to migraine sensitisation, said Dr Jenkins.

“It’s exciting to have a better preventer potentially because the chronic migraine group can get into a vicious cycle of medication overuse – and preventers are really the only way forward for them,” she said.

Erenumab (Aimovig) has recently been under consideration for PBS subsidy but was declined at a March 2019 meeting of the Pharmaceutical Benefits Advisory Committee (PBAC) on the grounds of uncertain cost-effectiveness, particularly when compared to Botox use. Galcanezumab (Emgality) will be considered at the next PBAC meeting in July 2019.

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