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Monoclonal Antibodies against CGRP (MAAC) or its Receptor (MAACR) and the Prevention of Migraines
Three new medications for migraine prevention were approved in 2018 and a fourth was approved in 2020. They are all monoclonal antibodies. Aimovig (erenumab) targets the CGRP receptor. Ajovy® (fremanezumab), Emgality® (galcanezumab) and Vyepti® (eptinezumab) target CGRP itself. Monoclonal Antibodies are like the smart missiles of the pharmaceutical industry. If you can write a check, then you can get monoclonal antibodies created against any protein in the human body. The technology is mature and is used for multiple diseases. The "warhead" of the antibody is the part of the antibody that attaches to the target. In the case of Aimovig - it is a Monoclonal Antibody against the CGRP receptor (MAACR). The other three are Ajovy, Emgality and Vyepti are Monoclonal Antibodies against CGRP (MAAC). In the absence of a head to head study between Aimovig and either Ajovy, Emgality, or Vyepti- it will not be possible to really determine which approach is superior. Since Aimovig was released first in April 2018, Dr. Loftus already has multiple patients who failed Aimovig waiting to try Ajovy - the second drug released. Some of those that failed Ajovy who had not previously tried Aimovig, did well with Aimovig.
These monoclonals are all FDA approved for prevention of migraine for both patients with episodic migraine (less than 15 headache days per month) and chronic migraine (more than 15 headache days per month). They are not more effective or less effective than the first line oral preventatives. or other migraine procedures. They do, however have two primary advantages. First, there is no dose titration for these treatments. They can literally start working at the initial dose. They also have either none, or very few, central nerve system side effects. There is certainly local discomfort from the shots themselves and some patients get an rash but this is infrequent. Vyepti is an injection so there are no local shot reactions to deal with. Aimovig, perhaps because it is a MAACR and not a MAAC, has small incidence of constipation and some muscle spasm at the higher of the two recommended dosing regimens. All of these medications medications have a 1/2 life of about 1 month. This means that it is 5-6 months after stopping a medication before it is completely out of the body. This could have serious implications for patients who get pregnant. The other concern with these new medications is we really do not know what will happen to someone who has their CGRP blocked for years or even decades.
How to choose between them? Do you care if you get an auto-injector or would you rather self inject (i.e. control the rate of injection yourself). Aimovig does not have a self-injector. Ajovy and Emgality has both. Would you rather treat quarterly or monthly? Ajovy and Vyepti offers quarterly dosing. Would you rather take you treatment at home or would you rather come to the doctors office once per quarter for an hour or so and have everything handled for you? Vyepti, being a 30 minutes office infusion, allows you to show up once per quarter and not have to worry about doing anything for yourself at home for prevention. If you are someone who has difficulty keeping to a schedule (getting a monthly medication and self injecting on time) then having the doctor's office do it can be a nice advantage.
These medications are roughly the same price as Botox® for chronic migraine. For those with commercial insurance, the medications are usually free. While it seems great for the individual patients, these discount programs causes the prices of medications in the US to increase rapidly and is probably one of the reasons why equivalent medications in the US are so much more expensive than other countries.