CGRP (calcitonin gene-related peptide) is a small signalling molecule released from trigeminal nerve endings during migraine attacks. It is the target of the most important new migraine treatment class in 30 years. Drugs that block CGRP or its receptor — both injectable monoclonal antibodies for prevention and oral gepants for acute treatment — have changed the therapeutic landscape since the first FDA approval in 2018.

This page covers what CGRP does, the medications that target it, and how it fits into Hermly’s role as a forecasting (not treatment) tool.

What CGRP does in migraine

CGRP is a 37-amino-acid peptide widely distributed in the nervous system. In the trigeminovascular system — the network of nerves that mediates head pain — CGRP is released by activated trigeminal neurons. Once released, it:

  • Causes vasodilation of cranial blood vessels.
  • Sensitises pain pathways, lowering the threshold for further pain signalling.
  • Contributes to neurogenic inflammation around blood vessels and the meninges.

The case for CGRP’s central role came together over two decades of research:

  • CGRP levels rise during migraine attacks.
  • Injecting CGRP into migraine patients reliably triggers attacks.
  • Blocking CGRP or its receptor relieves attacks and reduces frequency.

That last finding — that blockade works — is what made the drug class possible.

The two drug classes

Monoclonal antibodies (for prevention)

Large protein drugs that bind to CGRP itself or its receptor, neutralising the signalling pathway for weeks at a time. Given by self-injection (monthly) or by infusion (quarterly).

  • Erenumab (brand name Aimovig) — receptor-targeting
  • Fremanezumab (Ajovy) — CGRP-targeting
  • Galcanezumab (Emgality) — CGRP-targeting
  • Eptinezumab (Vyepti) — CGRP-targeting, IV infusion

Typical efficacy: roughly 50% of patients experience a 50%+ reduction in migraine days. Generally well-tolerated with mild injection-site reactions and constipation as the most common adverse effects.

Gepants (small-molecule receptor antagonists, for acute or preventive use)

Oral medications that block the CGRP receptor pathway with shorter duration of action than the antibodies.

  • Ubrogepant (Ubrelvy) — acute treatment
  • Rimegepant (Nurtec ODT) — acute or every-other-day preventive
  • Atogepant (Qulipta) — daily preventive
  • Zavegepant (Zavzpret) — nasal spray for acute treatment

The 2023 PRODROME trial showed ubrogepant taken during the prodromal phase reduced progression to moderate-or-severe headache — the first solid evidence for treating before pain begins with a CGRP-targeted drug.

Why this matters clinically

Before the CGRP era, prevention options were repurposed from other conditions: beta blockers, anticonvulsants, antidepressants, botulinum toxin. They worked for some patients, had significant side-effect profiles, and were not designed for migraine.

CGRP drugs are the first preventive class designed specifically for migraine biology. They’re often better tolerated and work in patients who failed multiple other preventives. Tradeoffs include cost (insurance coverage varies widely) and the relative novelty — long-term safety data is still accumulating.

For acute treatment, gepants offer an alternative to triptans without the vasoconstrictive cardiovascular contraindications. This matters for older patients and those with cardiovascular risk factors.

What Hermly does (and doesn’t) do with CGRP

Hermly does not:

  • Recommend or prescribe any specific medication, including any CGRP-class drug.
  • Notify you to take medication on a high-risk forecast.
  • Differentiate forecast behaviour based on what preventive medication you’re on.

Hermly does:

  • Let you log any medication (CGRP-class or otherwise) during attacks via the Live Activity, Action Button, or Siri intents.
  • Track medication frequency in the rolling 30-day window so MOH risk is visible (see our MOH page).
  • Surface that data in the doctor report so you can show your prescriber the actual frequency of acute medication use.

The decision of whether a CGRP drug is right for you is a real medical conversation with a neurologist or headache specialist. Cost, insurance coverage, baseline attack frequency, prior treatment history, and pregnancy plans all factor in. Hermly does not participate in that conversation.

What this isn’t

Not a guide on whether to ask for a CGRP medication. The shared decision between you and your clinician is the right venue for that. Hermly’s role is to make your attack patterns legible — and if a CGRP drug is what your clinician recommends, Hermly will track whether your forecast and attack frequency change after starting it.