Gepants – more migraine drugs we’re missing out on

The new vogue of migraine medications are those that block calcitonin gene-related peptide (CGRP), a small protein found in the nervous system involved in the processing of pain.

The role of CGRP in migraine was confirmed by a study that injected CGRP into people with migraine, which provoked migraine attacks.

Since then, the search has been on for drugs that target CGRP and treat migraine. The first of these were the gepants, small molecules designed to block CGRP receptors, where CGRP would bind to stimulate electrical signals, and in the case of migraine, kick off the translation of a sensory stimulus into the perception of pain.

These were effective but had toxic side effects, so researchers tried a different approach – monoclonal antibodies. Antibodies are proteins that find and stick to another protein. Monoclonal antibodies are man-made, designed to target a specific protein, in this case CGRP or its receptor.

This led to the successful development of erenumab (which targets the CGRP receptor), galcanezumab, fremanezumab and eptinezumab (which target the CGRP molecule itself). Two of these (erenumab, brand name Aimovig, and galcanezumab, brand name Emgality) are currently available in Aotearoa New Zealand, albeit not funded. They’re used for the prevention of migraine attacks.

One issue with monoclonal antibodies is that they’re large, poorly absorbed by the gut and are quickly broken down by gut bacteria, which means they must be injected, either into a vein or through the skin.

Researchers returned to investigating the gepants, which can be taken by mouth. They created a second generation of gepants without the toxic side effects and found that they could be effective at relieving the pain of a migraine attack, making them a useful alternative to triptans.

Unlike triptans, gepants don’t constrict blood vessels, making these a safe option for people with cardiovascular disease. Currently, there are three gepants approved by the FDA (the US organisation that evaluates and approves medications) for acute migraine attacks: ubrogepant as a standard tablet (brand name Ubrelvy), rimegepant as a dissolvable tablet (brand name Nurtec in the US or Vydura in Europe) and a nasal spray version (zavegepant).

One major benefit from the gepants is that unlike other pain relievers taken for migraine (including triptans), they don’t appear to cause medication overuse or rebound headaches and cause very few side effects.

Gepants can also be used for migraine prevention. The FDA has approved rimegepant (Nurtec/Vydura) and atogepant (brand name Qulipta) for this indication. Atogepant (Qulipta) was developed solely as a migraine prevention agent.

These drugs are the first of their kind – the first drugs developed specifically for migraine after pure science research identified a pathway in the brain responsible for migraine symptoms. But no gepants are available in Aotearoa New Zealand.

One of our priorities is to advocate for access to new treatments. To help us do that, we need more information about the impact of migraine on people in New Zealand and what type of treatments people are taking or have taken in the past.

Our online survey in 2022 has helped provide us with data about the migraine burden in New Zealand. Stories from people living with migraine can also be a powerful influence. If you would like to share a story about how migraine has affected your life and what it would mean to you to have more treatment options, please contact us at

Further reading