Galcanezumab, the third CGRP monoclonal antibody for migraine is approved
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.
Has anyone had a colitis relapse with Emgality? I have Lymphocytic microscopic colitis (MC-LC) and seem to have gone into a colitis relapse since the initial injections. Perhaps simply coincidence. Or perhaps what causes some to suffer constipation causes me the opposite.
The official FDA-approved package insert lists constipation as a side effect of Aimovig (erenumab), but not Ajovy (fremanezumab) or Emgality (galcanezumab), but considering that they have a similar mechanism of action, it is not surprising that all of them could cause constipation. Their mechanism of action is similar but not identical – Aimovig blocks CGRP receptor while Ajovy and Emgality block the CGRP molecule. Our experience suggests that Aimovig indeed causes constipation much more often and we tend to avoid it in patients who are prone to constipation.
I started using Emgality with my first two injections. At first I didn’t relate my constipation to the the shots. However with my next injection a month later I knew Emgality was the cause of my severe constipation. It has totally paralyzed my digestive system. I have been taking fiber drinks, eating so many prunes, taking laxatives, fiber foods and this experience has me afraid my system will not go back to normal. I will not be taking another injection of Emgality. Horrible experience. Horrible drug.
Please report your experience with Aimovig to Amgen, the manufacturer or the FDA – it is very important to collect this information and warn doctors and other patients.
Yes, Botox is the recommendation of my PCP. I don’t dare try Emgality after this. Unfortunately, I cannot get in to see my neurologist until the end of February, so I will be patient until then.
I would definitely avoid galcanezumab (Emgality) as well. Botox is always my first choice for chronic migraines because of its 30-year safety record and high efficacy.
I am a 60 year old female who has suffered with chronic migraines without aura since puberty. The only maintenance drug that worked was Amitriptyline, however, I soon developed a right bundle branch block, so it was stopped. Triptans have been very successful. I recently participated in the Phase Three trial of fremanezumab (the double-blind study as well as the open study) with moderate success. In the open trial, my headaches were reduced by half and my abortive meds seemed to work more rapidly. Last October I chose to start the erenumab injections as I really wanted the auto-injector instead of a pre-filled syringe. I was prescribed two injections per month. About three days after the first set of injections, I had a mild migraine. I had no more headaches until a few days before the next set of injections was due. For the second month, I had zero headaches! I did have constipation but took a daily stool softener to help. I was so thrilled with this result, however, about two weeks into the first month I developed severe Raynaud’s Phenomenon symptoms (never having had them before). My fingers literally turned blue and stayed that way for 12 hours in addition to the tips of my index fingers and thumbs turning white and numb. I suspected that erenumab may be to blame since it was the only thing that had changed in my daily life. I opted to give that second month a try with more blue fingers and an episode of blood pooling at the base of my index finger for three days! Unfortunately I have had to stop the injections. My last set of injections was Thanksgiving Day. Although my finger tips still turn white and numb, they no longer turn blue. I have not tried Botox but that may be next on my list. I am heartbroken that I cannot continue on this drug.
I have had severe migraine for over 50 years, and Botox was marginal at best in controlling severity, if not frequency. I have been status migrainosus with the longest unresolved migraine of 21 days. I started Emgality three weeks ago and the effects are truly remarkable. Within one day I no longer had a migraine, and that has effectively continued for the three weeks. No side effects at all except the flattened wallet from the costs. I have the ability to try Aimovig in the future so will try that should the Emgality fail in continued efficacy. The best Christmas gift ever…no migraines after 50 years.
Thank you, Concerned for this information.
If you click on the link in the Concerned’s comment you can download a detailed review by the CENTER FOR DRUG EVALUATION AND RESEARCH, a division of the FDA. I did not find that the report minimized adverse events, but as the Concerned suggested, read it and decide for yourself. It is a lengthy report, so here is the summary section:
Benefit-Risk Summary and Assessment
Erenumab is a monoclonal antibody that antagonizes the calcitonin gene-related peptide (CGRP) receptor. It is indicated for the for the preventive treatment of migraine in patients with episodic and chronic migraine. Erenumab is given once monthly by subcutaneous injection.
Migraine is a very common, chronic neurological condition with a broad spectrum of frequency and severity. It is characterized by recurrent attacks of headache with accompanying symptoms of nausea, vomiting, photophobia, and phonophobia. These attacks are generally of moderate to severe intensity and can at times be disabling and impact the quality of patients’ lives. There are several FDA approved drugs for the preventive treatment of migraine. They have limitations related to tolerability and to their frequency or route of administration.
The efficacy of erenumab was demonstrated in three randomized clinical trials. Two trials were conducted in episodic migraine and one trial was conducted in chronic migraine. Both erenumab 70mg and 140mg demonstrated reduction in monthly migraine days as compared to placebo. In episodic migraine trials, patients had a baseline of about 8 migraines per month. Erenumab reduced monthly migraine days by about 1 to 2 days compared to placebo. In the chronic migraine trial, patients had a baseline of about 18 migraines per month. Erenumab reduced monthly migraine days by about 2 to 3 days compared to placebo. Reduction of the number of monthly migraine days a patient experiences may lead to decreased disability, fewer days in bed, and a reduction in the use of acute migraine treatments that have their own side effects and risks.
The safety profile of erenumab was characterized in three pivotal trials and one dose-ranging trial. No major, serious toxicities were identified in these trials that were definitively drug related. Adverse events in clinical trials included muscle cramps, constipation, viral infections, injection site reactions, cough, and pruritus. Clinical trials included generally young, healthy patients and excluded patients over age 65. Patients with major pre-existing cardiovascular disease were effectively excluded. A few events suggestive of ischemia were identified in the review including transient ischemic attack (TIA), myocardial ischemia, ischemic colitis, worsening Raynaud’s syndrome, and two cardiac deaths. Due to the mechanism of action of erenumab, these cases were examined carefully and did not appear to be drug related.
I recommend a postmarketing requirement (PMR) to study safety in patients over age 65. I recommend a PMR for a pregnancy registry study. These PMRs combined with enhanced pharmacovigilance, and product labeling will address the risks associated with erenumab in the postmarket setting.
I recommend approval of both the 70mg and 140mg dose of erenumab. Erenumab represents an additional therapeutic option for patients with migraine headache. The efficacy of the product is similar to other products approved for the preventive of migraine. The tolerability of the product appears to be an improvement over other approved products. The product is given once monthly which may improve compliance over drugs that need to be taken daily.
Dr. Mauskop says: “This lack of any serious side effects, contraindications or drug interactions (as far as we know so far) is unlike any other group of drugs known to medicine.”
Read the report on Aimovig from the FDA and note for yourself. They minimized nearly ALL of the adverse events. There are CGRP receptors in all major body systems and this drug would have the ability to affect all of them. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761077Orig1s000MedR.pdf
Yes, erenumab (Aimovig) blocks the receptor, while fremanezumab (Ajovy) and galcanezumab (Emgality) block the CGRP molecule, but their efficacy appears to be very similar. It is conceivable that if erenumab does not help, one of the other two drugs might because of the difference in the mechanism of action. I have only a couple of patients who switched and it is too early to tell. I would not give erenumab and one of the other drugs at the same time since it would block too much of the CGRP effect in the body and could lead to more side effects.
Thanks for your great info on this blog.
Given the two different CGRP approaches ie, targeting the molecule vs. targeting the receptor, do you think there would be benefit of taking both types?
Fortunately, you do not have to pick between Aimovig and Bootx. If your insurance agrees to pay for only one of these two treatments, pick Botox because Aimovig’s manufacturer offers various discounts and even free drug, if you qualify.
Thank you for the ongoing updates on the CGRP medications. As a daily headache sufferer, I am anxiously awaiting my first injection of Aimovig. I will keep using Botox too, even if I have to pay for the treatments out of pocket. Please continue to keep us updated on your patients’ experiences.
It is not very surprising that the side effects would be similar in all 3 CGRP monoclonal antibodies, even though fremanezumab (Ajovy) and galcanezumab (Emgality) do not list constipation as a side effect. The exact mechanism is not clear, but CGRP is a ubiquitous molecule which is present throughout the body with a wide variety of effects. Actually, it is very surprising that these drugs don’t have more side effects. This lack of any serious side effects, contraindications or drug interactions (as far as we know so far) is unlike any other group of drugs known to medicine.
I took a dose of Ajovy and within a week started to have constipation. Disappointing!
How do these drugs cause constipation?
Yes, we have seen patients who take triptans daily respond well to erenumab (Aimovig) and chances are that the other two CGRP drugs, fremanezumab (Ajovy) and galcanezumab (Emgality) will work equally well. Triptans rarely cause rebound, or medication overuse headaches. Daily use of triptans is the topic of my most popular blog post – it has over 250 comments.
Genomind panel does not include anything that is related to CGRP drugs and we don’t even know if such a genetic test will ever be discovered. We do know that patients who have elevated CGRP levels during a migraine attack are more likely to respond, but such a blood test is not available outside experimental laboratories.
Hi Dr. Mauskop. Question, if my son does well on Triptans but hasn’t done well on preventative meds (other preventative meds made Headaches worse) would you think that the CGRP shot would be a possible good fit? He is actually taking Triptans almost daily which really help but lately his headaches are coming back and/or lingering throughout the day (just a little bit) – the minute I think it’s due to medication over use headaches than it will by almost 2 days before he needs another Triptan. We are so frightened to try the CGRP drug because of the bad side effects he has gone through with preventatives – Topomax caused dizziness and rashes, Amitriptyline caused him some pretty bad anxiousness, Gabapentin caused bad stomach issues. Our migraine specialist would like us to try it when we are ready but we are waiting and watching for a bit. The good thing is my sons headaches aren’t really migraines anymore they are lower in level thank goodness. So my other question is, will these injections (CGRP drug) work if someone is in a possible medication over use with Triptans? Thank you in advance for your opinion 🙂 We have recently tested him through Genomind, I wonder if any of these results would show how he would do on CGRP drug?
Yes, we’ve seen a few patients who felt that erenumab (Aimovig) made their headaches worse and a couple felt that the frequency of attacks went down while the severity increased. This should not be too surprising since almost every drug we use to treat headaches make headaches worse in a small number of patients. This applies to triptans, beta blockers, antidepressants, Botox, and other medications. The effect of Aimovig, a single shot of fremanezumab (Ajovy), and galcanezumab (Emgality) lasts about a month, at which point the blood level is at half of the peak level. So, because some of the medicine is still in circulation the effect and the side effects could last longer.
I injected Aimovig for four months (two months at 70 mg and two months at 140 mg). As far as I can tell, it worsened my headache pattern significantly! My daily headaches are worse, my migraines more frequent and my rescue medications are less effective. Have you had that experience with any of your patients? Since injections are monthly, I assume the effects are prolonged. How long does Aimovig take to clear the body completely? I’m (impatiently) waiting for its effects to wear off. Thanks!