Anti-CGRP monoclonal antibodies
In 2018, the US Food and Drug Administration approved for migraine prevention 3 new monoclonal antibodies that target CGRP or its receptor: erenumab, fremanezumab, and galcanezumab. CGRP antagonists represent the first class of medications to target specifically the pathophysiologic processes implicated in migraine. Thus far, clinical trial data indicate that these 3 agents have comparable efficacy, are well tolerated, and are not associated with safety issues.
Calcitonin Gene-Related Peptide (CGRP)
CGRP is a neuropeptide widely distributed in the nervous system, where it is thought to play a role in several processes, including vasodilation of cerebral and dural vessels, release of inflammatory mediators and transmission of nociceptive signals to the central nervous system.
The underlying pathophysiology of migraine is largely unknown, but calcitonin gene-related peptide (CGRP) most likely plays an important role. The first time CGRP was hypothesized to be involved in migraine was in 1985. This hypothesis was later supported by the finding of CGRP release during acute migraine attacks and the subsequent demonstration of normalization of CGRP levels in migraine patients after efficacious sumatriptan treatment.
Several lines of evidence support the role of CGRP in migraine:
- In the absence of triggers or during treatment, it has been noted that migraine patients’ CGRP levels remain lower.
- Elevations in serum and salivary CGRP have been observed in both spontaneous migraine attack and nitric oxide-induced attack.
- Intravenous CGRP can induce a migraine attack in a matter of hours in migraine patients. This was not observed in people who do not suffer from migraine.
Two Kinds of Anti-CGRP Medications (Oral VS mAbs):
Oral anti-CGRP medications called ‘gepants’ were initially developed and tested in the early 2000s but the discovery of liver toxicity with its use caused many drug companies to stop pursuing this class of drugs. With many drug companies halting the development of gepants, the use of monoclonal antibodies (mAbs) to target CGRP molecules and its receptors were developed. Monoclonal antibodies are proteins that use the immune system to target specific molecules inside your body. Currently, there are four anti-CGRP mAbs that have been developed, galcanezumab, eptinezumab, erenumab, and fremanezumab.
The first calcitonin-gene receptor peptide (CGRP) drug for treating migraines has been approved by the FDA this year with the introduction of Aimovig by Amgen and Novartis. Erenumab binds to the CGRP receptor and blocks the CGRP receptor function. The administration is monthly subcutaneous injections. The recommended dose of erenumab is 70 mg once monthly. Some patients may benefit from a higher dose of 140 mg once monthly, which is administered as two consecutive subcutaneous injections of 70 mg each.
The FDA’s approval for Aimovig was based on results obtained from a Phase IIIb clinical study known as LIBERTY. It was a multi-centre, double-blind, placebo-controlled study that enrolled 246 patients with episodic migraine who had between two and four unsuccessful treatments. The patients were randomised to receive either 140mg Aimovig or placebo for 12-weeks. The primary endpoint of the study was the percentage of patients with at least a 50% reduction of monthly migraine days from baseline over the last four weeks of the study. The most common adverse reactions found in patients treated with Aimovig were injection site reactions and constipation.
Patients treated with Aimovig showed significant reductions in the number of migraine days each month during the extensive clinical programme that involved the participation of 2,600 patients. The safety and tolerability profile of the drug was found to be similar to placebo.
Aimovig is now licensed for use in the UK. It has been approved for prophylaxis of migraine in adults who have 4 or more migraine days per month. It is not yet available on the formulary in most NHS hospitals but Dr. Krishna is able to prescribe it privately. Please contact us if you need further information.