Galcanezumab (Emgality) was the third drug in the family of CGRP monoclonal antibodies (mAbs) to become approved by the FDA for the prevention of migraines. It is more similar to fremanezumab (Ajovy) in its mechanism of action than to erenumab (Aimovig). Erenumab is an antibody that blocks the CGRP receptor, while galcanezumab and fremanezumab are antibodies that block the CGRP molecule. This may explain the fact that some patients who do not respond to one of these drugs may respond to another. Actually, even patients who do not respond or respond only partially to fremanezumab may respond to galcanezumab and the other way around. This should not be surprising since many drugs with the same mechanism of action may have different efficacy and side effects in different patients. In migraine treatment this applies to triptans, such as sumatriptan (Imitrex), rizatriptan (Maxalt), eletriptan (Relpax), and other, as well as beta blockers, such as propranolol (Inderal), atenolol (Tenormin), nebivolol (Bystolic).

Just like the other two CGRP mAbs, galcanezumab is injected monthly (although fremanezumab can be also given at a triple dose every three months). The initial dose is 240 mg, or two auto-injector pens, followed by a monthly dose of 120 mg. The main side effects are similar to the other two drugs, namely injection site reactions such as swelling, redness, and an allergic rash. Erenumab can be constipating, while the other two drugs are much less so.

The cost of all 3 drugs is the same – between $550 and $600 per monthly injection, but most insurers will pay for them if certain conditions are met. The main condition is that the patient first try and fail two oral preventive medications such as beta blockers listed above, an antidepressant such as amitriptyline (Elavil), nortriptyline (Pamelor), or duloxetine (Cymbalta), or an epilepsy drug such as topiramate (Topamax) or divalproex sodium (Depakote).

Another, more recent requirement from many insurers, is that the patient not be receiving Botox. This prohibition is very upsetting because it is not based on any science and because many patients find that together these treatments (Botox and a CGRP mAb) provide almost complete relief of their migraine attacks. Both Botox and CGRP mAbs can be life-changing on their own with dramatic relief in about 20% of patients, while another 50% of patients obtain only partial relief. This is a very rational combination because these treatments work in a totally different way and both are extremely safe with no drug interactions. The insurers justify their refusal by the fact that there are no published studies showing the safety of this combination, which is ludicrous. Some insurers, such as Cigna, go a step further in their obnoxiousness – even if a patient gets free mAb from the manufacturer or pays out of pocket, they refuse to pay for Botox. How do they know if the patient is getting a mAb? – to get prior approval for Botox we have to submit our medical notes.

All three manufacturers of mAbs, Amgen, Teva, and Eli Lilly provide up to one year of free medicine if your commercial insurance refuses to pay for it. Check each manufacturer’s website – Aimovig.com, Ajovy.com, and Emgality.com. Allergan, Botox manufacturer offers up to $700 off each quarterly treatment, so if you are paying out-of-pocket or have a high copay or deductible, check BotoxSavingsProgram.com 

Fremanezumab (Ajovy) is the second CGRP monoclonal antibody to become after the introduction of erenumab (Aimovig) and it has some differentiating features. I injected myself with Aimovig twice and was able to drink more wine with relative impunity. The relief from my migraines was not complete, but very significant. However, I did experience constipation, which was quite unpleasant. Constipation is the only side effect of Aimovig reported with any frequency besides injection site reactions (an allergic rash can also occur). As one gets older (and I am 62), constipation becomes more prevalent. Although I could manage the constipation, it took an effort and I did not continue with Aimovig. My migraines are not at all disabling and I just cut back on wine. Besides wine, sleep deprivation and certain foods trigger my migraines, but they are easily managed with sumatriptan tablets or when I want fast onset of action, with sumatriptan injections.

After a couple of months, I decided to try Ajovy and took a shot on November 6. It worked at least as well as Aimovig and did not cause constipation. The effect lasted exactly a month and then migraines returned, so I took a second shot on December 13. Both Ajovy injections started to work within a day, although in some of my patients it takes a week.

I continue to prescribe Aimovig as well as Ajovy and sometimes, the third drug in this family, galcanezumab (Emgality). If someone is prone to constipation, my first choice is definitely Ajovy. Another small difference is the mode of delivery. You can give yourself a shot of Aimovig (and Emgality) with a push of a button, while Ajovy comes in a pre-filled syringe. Some patients find autoinjectors painful and opt for the prefilled syringe of Ajovy . Others, do not want to see the needle and prefer Aimovig’s pen-like device. One additional advantage of Ajovy is that it can be given every 3 months, although it requires 3 shots each time. Some of our patients who do not like giving themselves any kind of an injection opt for coming for a visit every 3 months and having our doctors or nurse practitioners administer Ajovy.

We have treated hundreds of patients with Aimovig and Ajovy and a few dozen with Emgality. Some who did not respond to Aimovig (we usually give two sets of monthly injections before giving up), responded well to Ajovy. This is probably due to the fact that they have a slightly different mechanism of action. Both are monoclonal antibodies that block the effect of CGRP, a neurotransmitter which is released during a migraine attack, but Aimovig blocks the CGRP receptor, while Ajovy (and Emgality) block the CGRP molecule. This difference may also explain why Aimovig constipates and the other two drugs do not.

About one fifth of patients have a dramatic relief from these medications, while about 50% have a 50% drop in the number of headaches. Some patients in the latter group may require continued treatment with Botox or oral medications, but together these treatments also result in a marked reduction in migraine-related disability. We also continue to prescribe abortive drugs such as sumatriptan (Imitrex) to all patients because even in complete responders an occasional migraine can still occur.

The FDA has just approved galcanezumab (Emgality), the third CGRP monoclonal antibody for the prophylactic treatment of migraines. It follows erenumab (Aimovig) and fremanezumab (Ajovy) and just like these two drugs it appears to be very safe and very effective for over 50% of patients.

Galcanezumab is also administered by a monthly subcutaneous injection. The initial dose is two 120 mg injections, followed by a single 120 mg injection every month. Similarly to erenumab, it comes in an autoinjector pen which is easy to self-administer. Fremanezumab is not available in an autoinjector pen but only in a small prefilled syringe, which may make some patients hesitant to use it, however injecting with a prefilled syringe is often less painful.

Galcanezumab and fremanezumab list as their only side effect injection site reaction, while erenumab also has the side effect of constipation. Erenumab was approved four months ago and at our Center we have already injected about 300 patients. Constipation is a problem for a small number of patients and in a couple of them it was severe enough that they stopped the injections.

Fremanezumab was approved only a couple of weeks ago and we’ve treated only about a dozen patients so far, so it is too early to tell if it will also cause constipation. After all, these three drugs are similar to each other in that they block the effect of calcitonin gene-related peptide (CGRP), a chemical released during a migraine attack. The only difference in the way they work is that erenumab blocks the CGRP receptor, where the CGRP molecule attaches itself, while the other two drugs block the actual CGRP molecule. It is possible that this difference in the mechanism of action is why erenumab is more likely to cause constipation.

We have also seen one patient who developed a rash about 5-6 days after being injected with erenumab, which resolved with a short course of prednisone.

All three manufacturers offer a free trial, in come cases for up to a year. Many insurers are starting to pay for these truly remarkable medications, although most require that the patient first tries and fails one or two inexpensive oral preventive medications. We’ve also encountered some insurers who will pay for either Botox or erenumab, but not for both. This is a problem for some of our patients who get partial relief from each treatment and almost complete relief when these two are combined. One strategy is to continue obtaining Botox through the insurance and getting one of the monoclonal antibodies through the free trial program.

One common question we get asked is how soon will the injection work. In some patients the relief begins in a couple of days, but we have also seen patients who improve only after 2 treatments. The large trials that led to the FDA approval suggest that each subsequent treatment will provide better relief than the previous one.

As expected, we’ve been overwhelmed by the demand for the new preventive therapy for migrianes, erenumab (Aimovig). It offers a unique and highly effective therapy with virtually no known side effects, at least so far.

My patients are usually glad to hear that I have migraines (without an aura, but I also have auras without a headache) because I can better relate to their experience. They often ask if I had tried this or another treatment and indeed, I’ve tried many, sometimes less out of necessity but more for the experience. I have never tried drugs such as topiramate (Topamax) or divalproex (Depakote) because they have many potentially serious side effects and I prescribe them very reluctantly after trying many other treatments. I have injected myself with Botox on two occasions, have given myself a nerve block and an intravenous infusion of magnesium.

Luckily, even when I have periods of very frequent attacks, my migraines are easily controlled with sumatriptan tablets or injections. I prefer injections when I want quick relief, such as before going to bed, in the middle of the night, or during a busy work day.

Although over 3,000 patients have been exposed to erenumab in clinical trials and some of them have been on it for 5 years, the true safety of the drug may not be known for at least another 3-5 years.

Even though my migraines do not cause any disability or interfere with my life (except for the need to avoid wine), in the tradition of doctors experimenting on themselves, yesterday I gave myself a shot of erenumab. It was painless and caused no local reaction, which is the most common side effect seen in 5%-6% of patients. This lack of serious and not so serious side effects has been the most surprising aspect of not only erenumab, but also of the other 3 CGRP monoclonal antibodies in development. So admittedly, injecting myself with erenumab was not an act of bravery and I really did it to see if I can drink more wine and take less sumatriptan.