The CGRP Antagonists: Revolutionary Breakthrough or 'Here We Go Again'?
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On May 17, erenumab (Aimovig) was approved by the FDA for the indication of migraine prevention, the first “designer drug” for migraine treatment since Glaxo’s injectable Imitrex was released almost 3 decades ago. Injectable sumatriptan (Imitrex) was a revolutionary drug, a true game-changer, that has empowered millions of migraineurs to rescue themselves from the misery of an acute severe headache attack.
Correctly assuming that Americans would prefer a pill over an injection, the pharmaceutical industry subsequently developed no less than 7 oral triptans, including an oral version of sumatriptan. None has proven to be nearly as effective as injectable sumatriptan for headache "rescue", and yet injectable sumatriptan remains woefully underutilized.
The oral triptans’ lukewarm therapeutic effect for the treatment of moderate to severe migraine led their makers to endorse the "early treatment paradigm", wherein patients were encouraged to take the medication when their headaches were still mild in intensity. Only problem: there is little or no evidence to indicate that the oral triptans are better for early treatment of mild to moderate migraine headache than other medications that are cheaper, more accessible or both.
Thus we are left with an obvious question: did we really need to develop 7 oral triptans?
Barring the unforeseen, erenumab (Aimovig) soon will be followed by at least 4 more CGRP antagonists for migraine prevention. Will this improve the standard of care for migraine or, as with the oral triptans, will we simply be confronted with another "me, too" glut?
A good question, but for now let’s focus on the pros, cons and unanswered questions regarding what is available: erenumab (Aimovig).
Pros
Significantly reduces headache burden in approximately 50% of patients with episodic or chronic migraine
Virtually free of short-term side effects
Theoretically (see below) is unlikely to cause long-term side effects
In contrast to BotoxA, can be self-administered by the patient
Improvement in responders tends to occur early, following the first or second treatment
No drug-drug interactions
Relatively inexpensive (approximately $6,900/year) compared to certain other therapies FDA-approved for migraine prevention
Low cost to patient
Cons
Fails to significantly reduce headache burden in approximately 50% of patients
As yet, no way to predict who will/will not respond
Limited experience with long-term use
Relatively expensive compared to certain other therapies widely used for migraine prevention
Questions
Will erenumab (Aimovig) work better, worse or the same as BotoxA or topiramate in suppressing chronic migraine?
Will it work in patients who have failed BotoxA?
Can we prospectively identify subpopulations of migraine patients more or less likely to respond to erenumab?
Will it work better if combined with another therapy for migraine prevention (e.g., BotoxA or topiramate)?
Will it work in patients overusing symptomatic medication?
Will long-term treatment result in the production of neutralizing antibodies that reduce or reverse erenumab’s therapeutic effect?
Will long-term treatment produce side effects that did not occur in the shorter-term clinical research studies that earned erenumab its FDA approval?
Can treatment with erenumab eventually be stopped?
Conclusions
Many pros
Few cons
A number of questions left to be answered
Mighty nice to have something new, safe and effective to offer patients
