Aimovig vs. Ajovy, Aimovig vs. Emgality, Aimovig vs Vyepti, Ajovy vs. Emgality, Emgality vs. Vyepti, Ajovy vs. Vyepti. So many questions. so many answers. Let’s discuss them all. This blog article will discuss and compare the 4 CGRP monoclonal antibody (CGRP mAb) migraine preventive treatments including Aimovig (Erenumab), Ajovy (Fremanezumab), Emgality (Galcanezumab), and Vyepti (Eptinezumab). Hopefully it will help you choose which one may be best for you.
So it finally happened! The 1st migraine specific preventive medications FINALLY became available with the CGRP (calcitonin gene related peptide) monoclonal antibody (CGRP mAb) antagonists which first came to market in Spring of 2018. Prior to 2018, all of the migraine preventive medication options had been “adopted” from other specialties.
For example, the 3 main categories of preventive medicines prior to 2018 were select evidence-based options within the anticonvulsant (anti-seizure), anti-depressant/anti-anxiety, and anti-hypertensive (blood pressure) medicine categories. These conventional migraine preventive treatments are still used, can be very effective, and are discussed in much greater detail here. Unfortunately, there were still many migraine patients that did not respond to these conventional options, or had side effects with them.
The gepants (Nurtec, Qulipta) have also now received FDA approvals for migraine preventive treatment. Other migraine preventive therapies include neuromodulation devices, Botox injections, or alternative treatments such as vitamins and supplements, acupuncture, acupressure and pressure points, or yoga and meditation.
What is Calcitonin Gene Related Peptide (CGRP), and how does CGRP relate to migraine?
CGRP plays a strong role in neurogenic inflammation in the nervous system and is involved in the transmission of pain. It is also a potent vasodilator (dilates blood vessels) which triggers more CGRP release and pain. It increases pain transmission and is a very potent inflammatory protein. In fancy headache specialist circles, you’ll hear this called “sterile neurogenic inflammation”. All of this essentially intensifies migraine pain and plays a role in triggering a migraine.
CGRP has been studied since the early 1980s when it was discovered. It was found throughout the trigeminovascular system and trigeminal cranial nerves which transmit pain, so a role in migraine was suspected. The trigeminal nerves and their associated electrical circuitry throughout the brain, brainstem, and arteries in the brain is called the trigeminovascular system. This system is the basis and “on switch” for migraine.
In the early 1990s it was shown that CGRP was released by the trigeminal nerves and levels increased during an acute migraine attack. In 2004, a CGRP antagonist (blocks the binding of CGRP to its receptor) was shown to abort an acute migraine attack, and decrease CGRP levels.
Subsequent studies including preventive migraine studies done since 2014 with a CGRP antibody to block the effects of CGRP eventually led to 3 FDA approved CGRP mAbs in 2018, and a 4th CGRP mAb FDA approved in 2020.
How are the CGRP mAbs made and what is the science behind them?
The CGRP mAbs are considered biologic drugs because they are made by the cells of living organisms. This is in contrast to conventional medications made by chemical synthesis.
The 4 CGRP mAbs are all classified as “humanized” monoclonal antibodies. Humanized CGRP mAbs are made in a laboratory by combining part of a human antibody with a small part of a non-human (such as hamster or yeast) monoclonal antibody by a process called recombinant DNA technology. The non-human part of the antibody binds to the target antigen (in this case, either the CGRP ligand (protein) or CGRP receptor), and the human part makes it less likely to be seen as a “foreign antigen” destroyed by our immune system.
To explain further, these humanized CGRP mAbs are produced and cloned repeatedly in non-human immune system living cells (hamster ovarian cells or yeast cells), ensuring that they are all of identical genetic material (monoclonal), and their protein structure is modified to increase their similarity to antibody structures produced naturally in humans.
As a review, antibodies are proteins made by living organism cells which bind unique parts of other proteins that are recognized as a “foreign” to that biologic system. For example, when your body is exposed to a virus or bacteria by infection or immunization, your body makes specific antibodies against that microbe to destroy it. If your body encounters that microbe in the future, it remembers it (immune response), and your antibodies attach to it to neutralize and destroy it. Similarly, the CGRP mAbs are made to bind either the CGRP protein itself, or the receptor where the CGRP binds (the migraine “on” switch).
How do the CGRP mAbs work for migraine?
The CGRP mAbs target either the CGRP receptor and block it (antagonist) to prevent the CGRP ligand (protein) from binding, or they target the CGRP ligand itself and prevent it from binding (sticking) to the CGRP receptor. Clinically, some patients tend to respond better to the CGRP receptor blockade, whereas others tend to do better with binding the CGRP ligand itself. There is not really any data on this in terms of who may respond to which type of CGRP mAb target, but I’m sure it will be studied further eventually.
In general, the CGRP mAbs tend to all be quite effective. However, the point is if one type of CGRP mAb doesn’t work, it doesn’t mean the others won’t work either. I have seen many patients who did not respond to one type of CGRP mAb, but responded dramatically well to another. So, if you do not respond to one type of CGRP mAb target (such as the CGRP receptor), it may be worth trying another type of CGRP mAb target (such as the CGRP ligand). The bottom-line is don’t lose hope if one type doesn’t work well for you!
The CGRP mAbs are administered by injection or infusion because oral absorption is poor and degradation in the gastrointestinal system would inactivate the antibodies before they would even be able to enter the circulatory system. They are systemically absorbed by transport through the lymphatic system and into the blood. Metabolism occurs in the reticuloendothelial system, not the liver or kidneys.
How effective are the CGRP mAbs?
All 4 of the CGRP mAbs have shown excellent tolerability, safety, and superior effectiveness in migraine prevention when compared to placebo. Compared to oral preventive therapies which have been the mainstay for decades (discussed here), the CGRP mAbs work much faster and do not require a slow dose titration, as is done with most oral preventives.
They are sometimes seen to be effective in just a few days, often within a month, and the data suggests that the longer a patient is on a CGRP mAb, the more effective it is. I typically recommend a minimum of at least 3 months, and if receiving some benefit at that point, at least 6 months is suggested.
The majority of CGRP mAb studies had at least 50% (half) of patients who were 50% responders (migraine days cut in half), which is great! In general, the CGRP mAbs provide an overall average net reduction of around 2 migraine days per month for episodic migraine and 4-6 days for chronic migraine. With that said, this number can be much higher depending on the patient and migraine characteristics being studied, such as baseline migraine frequency.
There are a group of patients that we see called “super responders” because they improve dramatically to having greater than 75% decrease in migraine days, and sometimes even no migraines. In the CGRP mAb studies, about 1/3rd of patients were “super responders”, with many them obtaining 100% reduction in migraine days. Although this is wonderful to see when it happens, it should not be the expectation or goal (nor should this be the goal with any preventive migraine treatment).
What are the CGRP mAb side effects and are CGRP mAbs safe in pregnancy and breastfeeding?
Side effects are minimal, and very similar to placebo in most of the studies, which is great compared to the frequent side effects seen with most of the oral preventive pills we often use. The most common side effects are listed in the table below, but mild injection site reactions tend to be the most common reported side effect among the 3 subcutaneous self-injection CGRP mAbs.
Cumulative data show no immunological (they do not suppress or alter the immune system because they do not have a target within the immune system), cardiovascular, or neurological safety concerns of significance. CGRP is suspected to play a possible role in regulating uteroplacental blood flow, myometrial and uterine relaxation, and in maintaining normal gestational blood pressure. Since the mAbs have a long half-life and can last in the system for 5 months, it is recommended to stop it about 6 months prior to pregnancy planning. The CGRP mAbs are also not recommended to use during breast-feeding since we do not have enough safety data at this time.
Can I still use my CGRP monoclonal antibody treatment (Aimovig, Ajovy, Emgality, Vyepti) with the Covid-19 vaccine?
The short answer is that we need to gather more data on this, so check back periodically for updates. However, this hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and CGRP mAbs, the same as any other vaccine. This has also been stated by the American Migraine Foundation.
Patients receiving CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti) were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that these treatments cannot be used along with receiving Covid-19 vaccination, nor do they need to be delayed or timed any differently in relation to receiving Covid-19 vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to Covid-19 vaccination because they are entirely different proteins with different mechanisms of action.
The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it. The CGRP mAbs do not have any significant influence on the immune system (they do not cause immunosuppression, etc.).
Rarely, the immune system of some patients can form neutralizing antibodies against the CGRP mAbs, and this can weaken the effectiveness of these treatments in their ability to decrease migraine frequency and severity. However, this rarity really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of these treatments, nor will these treatments lessen the effectiveness of the Covid-19 vaccine.
Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination, but not with Botox or the CGRP mAbs. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines. The topic of Covid-19 headache, Covid-19 vaccination, and the use of Botox is discussed further here.
Can I use a CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with Botox injections?
Insurance companies often present various hurdles to using preferred treatment options (the bane of my existence). One common issue for patients with chronic migraine who are receiving Botox injections is that most insurance companies will now make the patient choose between Botox or the CGRP mAb. There is of course no good scientific basis for this, other than the company doesn’t want to pay for both.
In fact, there is evidence that using Botox with the CGRP mAbs works better together than with either individually. An abstract presented at the American Headache Society Annual Scientific meeting in June 2020 showed that in patients with chronic migraine and a baseline frequency of 25.7 days per month, the frequency dropped to 14.8 days with Botox, and 9.1 days with Botox plus a CGRP mAb.
Can I use a CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with the gepants (Nurtec, Ubrelvy, Qulipta, Zavspret)?
A similar insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy, Zavegepant), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, but again, no good scientific basis.
Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and they had added erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec.
So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Theoretically, it would make sense that benefit would be greater with both classes of medicines combined because they are different types of medications targeting aspects of the same migraine pathway simultaneously (either targeting the CGRP receptor or the CGRP ligand protein). Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.
There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.
On 5/27/21, the oral pill Nurtec (Rimegepant) ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and remains the only option with this flexibility. It also became the first oral CGRP preventive gepant medication with this approval. It is used as a migraine abortive once per 24 hours as needed for migraine, or as a migraine preventive by using it every other day. Both doses are a simple 75 mg dissolvable tablet.
On 9/28/21, Qulipta (Atogepant) became the second oral CGRP preventive gepant medication to become FDA approved for migraine prevention. It is taken once daily. It is the first and the only gepant medication created and studied purely for migraine preventive use only.
So these 2 options have become the first oral CGRP preventive medication options. They are both of the gepant medication family, which is different than the CGRP mAb family, but none the less now offer an oral alternative to once monthly injections.
The gepants (Nurtec, Qulipta) and the CGRP mAbs (Aimovig, Ajovy, Emgality, Vyepti) are all compared to each other in more detail here.
Clinical comparisons of the CGRP mAbs
There are currently 4 CGRP mAbs available, and each is detailed and compared below in order of FDA approval and becoming available for use. There are some characteristics for each one which can be used to fine tune selection based on specific patient clinical perspectives. The bottom line is that the CGRP mAbs as a class are all very effective for the majority of patients. Ultimately, the one prescribed will often depend on insurance formulary preferences, but there are no “bad options” among them!
Aimovig (Erenumab)
Aimovig was the first of the CGRP mAbs to come on the scene. It is made by Amgen and was FDA approved for migraine prevention 5/17/18. The antibody is produced by recombinant DNA technology in Chinese hamster ovary cells. It is the only one thus far which targets the CGRP receptor rather that the CGRP ligand (protein) itself. Therefore, it binds to the receptor, blocking the ability of the CGRP ligand to bind to the receptor and activate the migraine.
How is Aimovig Dosed?
It is dosed by either a 70 mg or 140 mg once monthly subcutaneous autoinjector. Since Aimovig came out first, we have longer term data available for it. At close to 5 years on the 140 mg dose, 77% of patients had a 50% reduction in monthly migraine days, 56% of patients had a 75% reduction in monthly migraine days, and 33% of patients had a 100% reduction in monthly migraine days. The dose can be administered to the abdomen, arm, buttocks, or thigh areas.
What are the side effects of Aimovig?
In post-marketing observations, there have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) in which most were not serious and occurred within hours of administration, and up to 1 week after. Nasopharyngitis was also a reported side effect in some patients.
Constipation was noted in the studies to occur in a very small percentage (1% for 70 mg, 3% for 140 mg). In post-marketing observations, there have been further reports of constipation with serious complications as well. Constipation occurs after the first dose in the majority of patients who will have this side effect (keep in mind the vast majority do not). Regardless, if you already have problems with constipation, I typically suggest trying one of the other CGRP mAbs (although it doesn’t mean it still can’t be tried). Vyepti and Ajovy have the least risk of constipation, and it is also rare with Emgality.
Post-marketing observations have also shown some worsening of pre-existing hypertension or development of hypertension. This observation was most frequently reported within 7 days of administration. Most of these patients already had pre-existing hypertension, or risk factors for developing it.
There is an Aimovig copay card on the company’s website in which most commercial insurance plans can get the medication for $5 per month.
Ajovy (Fremanezumab)
Ajovy was the 2nd of the CGRP mAbs to come along. It is made by Teva and was FDA approved for migraine prevention 9/14/18. It is produced by recombinant DNA technology in Chinese hamster ovary cells. It targets the CGRP ligand, rather than the CGRP receptor. It binds to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine.
How is Ajovy dosed?
Ajovy is dosed by either a 225 mg once monthly or 675 mg once quarterly autoinjector or syringe. The dose can be administered to the abdomen, arm, buttocks, or thigh areas.
What are the side effects of Ajovy?
There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as well, typically mild to moderate and occurred hours to 1 month after administration. Nasopharyngitis was also a reported side effect in some patients.
Ajovy has the least potential for constipation (along with Vyepti), so if that is an ongoing significant issue for a patient, then I typically suggest trying Ajovy first.
Ajovy also has the longest half-life, so if the patient tends to wear off early towards the end of the month, it may help to extend relief closer to the next monthly injection.
Of note, in the Ajovy chronic migraine studies, all patients receiving medication were given a loading dose of 675 mg for dose 1 followed by the standard 225 mg each subsequent month. However, this is not how it is normally dosed clinically for patients doing monthly treatments of 225 mg (no loading dose). Therefore, this initial loading dose could have potentially influenced some of the subsequent data.
There is an Ajovy copay card available on the company’s website in which most commercial insurance plans can get the medication for $5 per month.
Emgality (Galcanezumab)
Emgality was the 3rd of the CGRP mAbs to come along. It is made by Eli Lilly and was FDA approved for migraine prevention 9/26/18. Notably, it is the only one which also has FDA approval for prevention of episodic cluster headache, which was received on 6/4/19. It is produced by recombinant DNA technology in Chinese hamster ovary cells. It targets the CGRP ligand, rather than the CGRP receptor. Thus, it binds to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine.
How is Emgality dosed?
It is dosed by a 240 mg subcutaneous autoinjector for the 1st month only, followed by a 120 mg once monthly injection thereafter. The higher initial loading dose allows for obtaining a rapid steady state concentration level in the blood compared to Aimovig and Ajovy. The dose can be administered to the abdomen, arm, buttocks, or thigh areas.
What are the side effects of Emgality?
There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as with all of the self-injection CGRP mAbs. Nasopharyngitis was also a reported side effect in some patients, similar to the other CGRP mAbs as well.
There is an Emgality copay card available on the company’s website in which most commercial insurance plans can get the medication for $0 per month.
Vyepti (Eptinezumab)
Vyepti was the 4th and most recent of the CGRP mAbs to become available. It is made by Lundbeck and was FDA approved for migraine prevention 2/21/20. The antibody is produced in Pichia pastoris yeast cells by recombinant DNA technology. It targets the CGRP ligand, rather than the CGRP receptor. It binds very strongly to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine.
How is Vyepti dosed?
Vyepti comes in 100 mg and 300 mg doses and is dosed once quarterly (every 3 months) by a quick 30-minute infusion. The 100 mg dose is the recommended starting dose which can be titrated as needed to the higher dose as needed.
Vyepti is the only intravenous (IV) option available. Since it is administered IV, it is 100% bioavailable compared to the bioavailability of the other subcutaneous injections of 50-82%. It also reaches Cmax (maximum concentration) in about 30 minutes compared to 5-7 days of the other subcutaneous injections. Therefore, not surprisingly Vyepti showed treatment benefit in the first 7 days, often as early as 1 day post treatment, and showed continued effect through week 4, which is great since many patients on the once monthly self-injection CGRP mAbs often report a wearing off effect as they are approaching their next due injection.
This is certainly a good first line consideration, but also a good option for patients who do not like the thought of giving themselves a once monthly shot, have injection site reactions, or have failed the other CGRP mAbs options. Studies have shown some impressive highlights compared to other mAbs. In both the chronic and episodic migraine studies, almost 31% of patients had 75% or more reduction in migraine days in the 1st month alone. In the chronic migraine studies, about 27% of patients had a 75% or more reduction in migraine days over the first 3 months with 100 mg. After the 2nd dose (months 4-6), this increased to over 39% of patients! In the episodic migraine studies, over 22% of patients had a 75% or more reduction in migraine days over the first 3 months with 100 mg. After the 2nd dose (months 4-6), this increased to over 33.5% of patients.
What are the side effects of Vyepti?
There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching). Nasopharyngitis was also a reported side effect in some patients, similar to the other CGRP mAbs as well.
There is a Vyepti coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per infusion every 3 months.
Data comparisons of the CGRP mAbs
The comprehensive table which follows compares all available data between the 4 CGRP mAbs, as I have compiled from a combination of published studies, scientific posters, and supplemental data provided from medical science liaisons from each company. I have highlighted some of the data throughout the table when it is a unique aspect or superior response in that category.
All 4 CGRP mAbs have variable highlights that makes them stand out from the others in various categories, but overall they are all very effective options as a medication class. It is important to realize that the data compiled in the table should not be considered as a direct head to head comparison between the medications, and not all data points were looked at for each drug.
For each CGRP mAb, there were variations and differences in many trial aspects such as the study designs, how responder rates were calculated, statistical analysis used, trial endpoints, some responses were based on open label portions of trials (in which patients typically report a higher response rate when they know they are receiving the drug and not placebo), varying definitions such as “headache of at least moderate severity”, what defined a “headache” or “migraine day”, preventive medications being used simultaneously, and baseline migraine frequencies included in the studies.
The extent of reduction in migraine days can be influenced by the patient’s baseline migraine frequency in both the episodic and chronic migraine studies (high frequency vs lower frequency). For example, some studies included patients with a much higher baseline migraine frequency, and thus the extent of their migraine day reduction may not be as great as a group studied with a lower baseline frequency to start with.
| Aimovig (Erenumab) | Ajovy (Fremanezumab) | Emgality (Galcanezumab) | Vyepti (Eptinezumab) | |
|---|---|---|---|---|
| Dosing | 70 mg or 140 mg once monthly by subcutaneous autoinjector | 225 mg once monthly or 675 mg once quarterly by autoinjector or syringe | 240 mg subcutaneous autoinjector for 1st month followed by 120 mg monthly | 100 mg or 300 mg quarterly by 30-minute intravenous (IV) infusion |
| Target | CGRP receptor | CGRP ligand | CGRP ligand | CGRP ligand |
| Half-life | 28 days | 31 days | 27 days | 27 days |
| Median Peak Serum Concentration | 6 days | 5-7 days | 5 days | 30 minutes (after infusion) |
| Steady State | 3 months | 168 days (6 months) | After the 240 mg loading dose | After 1st dose |
| Bioavailability | 82% | 54-57% | N/A | 100% |
| Episodic migraine: Reduction in mean monthly migraine days in month 1 | 70 mg: -2.32 days 140 mg: -2.72 days Placebo: -0.9 days | 675 mg quarterly: -3.3 days 225 mg monthly: -3.5 days Placebo: -1.7 days | N/A | N/A |
| Episodic migraine: Reduction in mean monthly migraine days in months 1-3 | N/A | 675 mg quarterly: -3.7 days 225 mg monthly: -3.4 days Placebo: -2.2 days *Months 1-3 in long term extension study (open label): 675 mg quarterly: -4.7 days 225 mg monthly: -4.8 days | 120 mg monthly: -4.1 days Placebo: -2.1 days | 100 mg: -3.9 days 300 mg: -4.3 days Placebo: -3.2 days |
| Episodic migraine: Reduction in mean monthly migraine days in months 4-6 | 70 mg: -3.2 +/- 0.2 days 140 mg: -3.7 +/- 0.2 days Placebo: -1.8 +/- 0.2 days | N/A | 120 mg monthly: -5 days Placebo: -3 days | 100 mg: -4.5 days 300 mg: -4.8 days Placebo: -3.8 days |
| Episodic migraine: Reduction in mean monthly migraine days in months 1-6 | N/A | 675 mg quarterly: -5 days 225 mg monthly: -4.9 days *months 1-3 placebo, months 4-6 open label | 120 mg: -4.3-4.7 days Placebo: -2.3-2.8 days | N/A |
| Episodic migraine: Reduction in mean monthly migraine days in months 1-12 | 70 mg: -4.22 +/- 0.22 days 140 mg: -4.64 +/- 0.19 days Placebo: -1.8 days | 675 mg quarterly: -5.2 days 225 mg monthly: -5.1 days *months 1-3 placebo, months 4-12 open label | 120 mg: -5.13 days *12 month safety study with no placebo | 100 mg: -4.6 days 300 mg: -5.2 days Placebo: -4 days *Reported as months 7-12 |
Episodic migraine: 50% or more reduction in migraine days in month 1 | 70 mg: 32.7% 140 mg: 35.5% Placebo: 15.5% | 675 mg quarterly: 44% 225 mg monthly: 47% Placebo: 25% | 120 mg: 50.8% Placebo: 23.7% | 100 mg: 59.3% 300 mg: 56.3% Placebo: 40.5% |
Episodic migraine: 50% or more reduction in migraine days in months 1-3 | 70 mg: 41.3% 140 mg: 48.1% Placebo: 26.3% | 675 mg quarterly: 44.4% 225 mg monthly: 47.7% Placebo: 27.9% *At month 3 alone (not averaged over months 1-3): 675 mg quarterly: 49% 225 mg monthly: 51% Placebo: 37% *At month 3 in long term extension study (open label): 675 mg quarterly: 59% 225 mg monthly: 61% | 120 mg: 55% Placebo: 32% *At month 2 alone: 120 mg: 54.1% Placebo: 34.5% *At month 3 alone: 120 mg: 57.7% Placebo: 37.9% | 100 mg: 49.8% 300 mg: 56.3% Placebo: 37.4% |
Episodic migraine: 50% or more reduction in migraine days in months 4-6 | 70 mg: 43% 140 mg: 50% Placebo: 26.6% | N/A | 120 mg: 67% Placebo: 43% *At month 4 alone: 120 mg: 65.2% Placebo: 41.9% *At month 5 alone: 120 mg: 68.6% Placebo: 43.7% *At month 6 alone: 120 mg: 66% Placebo: 44.8% | 100 mg: 62% 300 mg: 65.3% Placebo: 51.4% |
Episodic migraine: 50% or more reduction in migraine days in months 1-6 | N/A | 675 mg quarterly: 65% 225 mg monthly: 60% *months 1-3 placebo, months 4-6 open label, data is at month 6 | 120 mg: 59.3-62.3% days Placebo: 36-38.6% | N/A |
Episodic migraine: 50% or more reduction in migraine days in months 1-12 | 70 mg: 61% 140 mg: 64.9% Placebo: N/A | 675 mg quarterly: 66% 225 mg monthly: 68% *months 1-3 placebo, months 4-12 open label, data is at month 12 | N/A | 100 mg: 64.7% 300 mg: 69.4% Placebo: 55.9% *Reported as months 7-12 |
Episodic migraine: 75% or more reduction in migraine days in month 1 | N/A | 675 mg quarterly: 20% 225 mg monthly: 22% Placebo: 10% | 120 mg: 25.7% Placebo: 6.5% | 100 mg: 30.8% 300 mg: 31.5% Placebo: 20.3% |
Episodic migraine: 75% or more reduction in migraine days in months 1-3 | N/A | 675 mg quarterly: 18.4% 225 mg monthly: 18.5% Placebo: 9.7% *At month 3 alone (not averaged over months 1-3): 675 mg quarterly: 30% 225 mg monthly: 29% Placebo: 10% | 120 mg: 30% Placebo: 14% *At month 2 alone: 120 mg: 31.2% Placebo: 11% *At month 3 alone: 120 mg: 34.2% Placebo: 12.8% | 100 mg: 22.2% 300 mg: 29.7% Placebo: 16.2% |
Episodic migraine: 75% or more reduction in migraine days in months 4-6 | 70 mg: 20.8% 140 mg: 22% Placebo: 7.9% | N/A | 120 mg: 42% Placebo: 24% *At month 4 alone: 120 mg: 41.6% Placebo: 15.2% *At month 5 alone: 120 mg: 41.4% Placebo: 15.5% *At month 6 alone: 120 mg: 43.9% Placebo: 15.8% | 100 mg: 33.5% 300 mg: 40.1% Placebo: 24.8% |
Episodic migraine: 75% or more reduction in migraine days in months 1-6 | N/A | 675 mg quarterly: 39% 225 mg monthly: 37% *months 1-3 placebo, months 4-6 open label, data is at month 6 | 120 mg: 33.5-38.8% Placebo: 17.8%-19.3% | N/A |
Episodic migraine: 75% or more reduction in migraine days in months 1-12 | 70 mg: 38.5% 140 mg: 40.8% Placebo: N/A | 675 mg quarterly: 42% 225 mg monthly: 45% *months 1-3 placebo, months 4-12 open label, data is at month 12 | N/A | 100 mg: 41.2% 300 mg: 47.7% Placebo: 32% *Reported as months 7-12 |
Episodic migraine: 100% reduction in migraine days in month 1 | N/A | 675 mg quarterly: 5% 225 mg monthly: 8% Placebo: 2% | 120 mg: 8.8% Placebo: 2.2% | 100 mg: 8.6% 300 mg: 14.9% Placebo: 5.9% |
Episodic migraine: 100% reduction in migraine days in months 1-3 | N/A | 675 mg quarterly: 0.7% 225 mg monthly: 2.4% Placebo: 0% | 120 mg: 11% Placebo: 4% *At month 2 alone: 120 mg: 11.8% Placebo: 3.7% *At month 3 alone: 120 mg: 12.2% Placebo: 7.3% | 100 mg: 11.4% 300 mg: 16.8% Placebo: 9.1% |
Episodic migraine: 100% reduction in migraine days in months 4-6 | 70 mg: 3.2% 140 mg: 5% Placebo: 2.8% | N/A | 120 mg: 17% Placebo: 9% *At month 4 alone: 120 mg: 16.3% Placebo: 8.5% *At month 5 alone: 120 mg: 17.6% Placebo: 8.7% *At month 6 alone: 120 mg: 16.5% Placebo: 9.5% | 100 mg: 19.8% 300 mg: 24.5% Placebo: 14.3% |
Episodic migraine: 100% reduction in migraine days in months 1-6 | N/A | 675 mg quarterly: 18% 225 mg monthly: 20% *months 1-3 placebo, months 4-6 open label, data is at month 6 | 120 mg: 11.5-15.6% Placebo: 5.7-6.2% | N/A |
Episodic migraine: 100% reduction in migraine days in months 1-12 | 70 mg: 19.8% 140 mg: 21.2% Placebo: N/A | 675 mg quarterly: 17% 225 mg monthly: 21% *months 1-3 placebo, months 4-12 open label, data is at month 12 | N/A | 100 mg: 26.8% 300 mg: 30.6% Placebo: 20.5% *Reported as months 7-12 |
| Chronic migraine: Reduction in mean monthly migraine days in month 1 | 70 mg: -5 +/- 0.42 days 140 mg: -5.1 +/- 0.42 days Placebo: -2.7 +/- 0.34 days | 675 mg quarterly: -4.8 days 225 mg monthly: -4.7 days Placebo: -2.7 days | 120 mg: -4.06 Placebo: -1.78 | N/A |
| Chronic migraine: Reduction in mean monthly migraine days in months 1-3 | 70 mg: -6.6 +/- 0.4 days 140 mg: -6.6 +/- 0.4 days Placebo: -4.2 +/- 0.4 days | 675 mg quarterly: -5 days 225 mg monthly: -4.9 days Placebo: -3.2 days *Months 1-3 in long term extension study (open label): 675 mg quarterly: -6 days 225 mg monthly: -6.7 days | 120 mg: -4.8 days Placebo -2.7 days *At month 2 alone: 120 mg: -5.01 Placebo: -3.04 *At month 3 alone: 120 mg: -5.41 Placebo: -3.39 | 100 mg: -7.7 days 300 mg: -8.2 days Placebo: -5.6 days |
| Chronic migraine: Reduction in mean monthly migraine days in months 4-6 | N/A | N/A | N/A | 100 mg: -8.2 days 300 mg: -8.8 days Placebo: -6.2 days |
| Chronic migraine: Reduction in mean monthly migraine days in months 1-6 | N/A | 675 mg quarterly: -6.5 days 225 mg monthly: -7.6 days *months 1-3 placebo, months 4-6 open label | N/A | N/A |
| Chronic migraine: Reduction in mean monthly migraine days in months 1-12 | 70 mg: -8.5 days 140 mg: -10.5 days Combined 70 mg and 140 mg: -9.3 days Placebo: N/A | 675 mg quarterly: -7.2 days 225 mg monthly: -8 days *months 1-3 placebo, months 4-12 open label | 120 mg: -7.21 *12 month safety study with no placebo | N/A |
Chronic migraine: 50% or more reduction in migraine days in month 1 | 70 mg: 23.9% 140 mg: 28.3% Placebo: 11.4% | 675 mg quarterly: 33% 225 mg monthly: 36% Placebo: 19% | 120 mg: 26.4% Placebo 11% | 100 mg: 54.5% 300 mg: 60.6% Placebo: 36.1% |
Chronic migraine: 50% or more reduction in migraine days in months 1-3 | 70 mg: 40% 140 mg: 41% Placebo: 23% | 675 mg quarterly: 30.7% 225 mg monthly: 33.3% Placebo: 19.9% *At month 3 alone (not averaged over months 1-3): 675 mg quarterly: 37% 225 mg monthly: 39% Placebo: 25% *At month 3 in long term extension study (open label): 675 mg quarterly: 42% 225 mg monthly: 48% | 120 mg: 27.6% Placebo 15.4% *At month 2 alone: 120 mg: 30.7% Placebo: 17.7% *At month 3 alone: 120 mg: 35.2% Placebo: 24.7% | 100 mg: 57.6% 300 mg: 61.4% Placebo: 39.3% |
Chronic migraine: 50% or more reduction in migraine days in months 4-6 | N/A | N/A | N/A | 100 mg: 61% 300 mg: 64% Placebo: 44% |
Chronic migraine: 50% or more reduction in migraine days in months 1-6 | N/A | 675 mg quarterly: 44% 225 mg monthly: 54% *months 1-3 placebo, months 4-6 open label, data is at month 6 | N/A, however: *At month 6 in open label extension trial: 120 mg: 44.5% | N/A |
Chronic migraine: 50% or more reduction in migraine days in months 1-12 | 70 mg: 53.3% 140 mg: 67.3% Combined 70 mg and 140 mg: 59% Placebo: N/A | 675 mg quarterly: 53% 225 mg monthly: 57% *months 1-3 placebo, months 4-12 open label, data is at month 12 | N/A, however: *At month 9 in open label extension trial: 120 mg: 53.9% *At month 12 in open label extension trial: 120 mg: 56.9% | N/A |
Chronic migraine: 75% or more reduction in migraine days in month 1 | N/A | Month 1 in long term extension study (open label): 675 mg quarterly: 21% 225 mg monthly: 21% | N/A | 100 mg: 30.9% 300 mg: 36.9% Placebo: 15.6% |
Chronic migraine: 75% or more reduction in migraine days in months 1-3 | 70 mg: 17% 140 mg: 20.9% Placebo: 7.8% | 675 mg quarterly: 9.6% 225 mg monthly: 12.3% Placebo: 5.4% *At month 3 in long term extension study (open label): 675 mg quarterly: 20% 225 mg monthly: 24% | 120 mg: 7% Placebo 4.5% | 100 mg: 26.7% 300 mg: 33.1% Placebo: 15% |
Chronic migraine: 75% or more reduction in migraine days in months 4-6 | N/A | N/A | N/A | 100 mg: 39.3% 300 mg: 43.1% Placebo: 23.8% |
Chronic migraine: 75% or more reduction in migraine days in months 1-6 | N/A | 675 mg quarterly: 28% 225 mg monthly: 24% *months 1-3 placebo, months 4-6 open label, data is at month 6 | N/A, however: *At month 6 in open label extension trial: 120 mg: 21.7% | N/A |
Chronic migraine: 75% or more reduction in migraine days in months 1-12 | 70 mg: 27.1% 140 mg: 41.8% Combined 70 mg and 140 mg: 33.2% Placebo: N/A | 675 mg quarterly: 28% 225 mg monthly: 31% *months 1-3 placebo, months 4-12 open label, data is at month 12 | N/A, however: *At month 9 in open label extension trial: 120 mg: 27.9% *At month 12 in open label extension trial: 120 mg: 31.1% | N/A |
Chronic migraine: 100% reduction in migraine days in month 1 | N/A | Month 1 in long term extension study (open label): 675 mg quarterly: 6% 225 mg monthly: 5% | N/A | 100 mg: 7.9% 300 mg: 13.4% Placebo: 2.7% |
Chronic migraine: 100% reduction in migraine days in months 1-3 | 70 mg: 4.3% 140 mg: 2.7% Placebo: 0.4% | 675 mg quarterly: 5.3% 225 mg monthly: 4.5% Placebo: 4% *At month 3 in long term extension study (open label): 675 mg quarterly: 5% 225 mg monthly: 6% | 120 mg: 0.7% Placebo 0.5% | 100 mg: 10.8% 300 mg: 15.1% Placebo: 5.1% |
Chronic migraine: 100% reduction in migraine days in months 4-6 | N/A | N/A | N/A | 100 mg: 17.8% 300 mg: 20.8% Placebo: 9.3% |
Chronic migraine: 100% reduction in migraine days in months 1-6 | N/A | 675 mg quarterly: 8% 225 mg monthly: 8% *months 1-3 placebo, months 4-6 open label, data is at month 6 | N/A | N/A |
Chronic migraine: 100% reduction in migraine days in months 1-12 | 70 mg: 6.1% 140 mg: 12.7% Combined 70 mg and 140 mg: 8.9% Placebo: N/A | 675 mg quarterly: 9% 225 mg monthly: 10% *months 1-3 placebo, months 4-12 open label, data is at month 12 | N/A | N/A |
Side effects: Nasopharyngitis | 70 mg: 3-9.9% 140 mg: 2-11% Placebo 6-10% | 675 mg quarterly: 5-8% 225 mg monthly: <1-8% Placebo: 4-9% | 120 mg: 7.4% Placebo: 6.5% | 100 mg: 6% 300 mg: 8% Placebo: 6% |
Side effects: Hypersensitivity reactions | 70 mg: <1% 140 mg: <1% Placebo : <1% | 675 mg quarterly: <1% 225 mg monthly: <1% Placebo: <1% | 120 mg: 1% Placebo: 1% | 100 mg: 1% 300 mg: 2% Placebo: 0% |
Side effects: Constipation | 70 mg: 1% 140 mg: 3% Placebo 1% | 675 mg quarterly: <1% 225 mg monthly: <1% Placebo: <1% | 120 mg: 1% Placebo: <1% | 100 mg: <1% 300 mg: <1% Placebo: <1% |
Side effects: Cramps, muscle spasms | 70 mg: <1% 140 mg: 2% Placebo <1% | 675 mg quarterly: <1% 225 mg monthly: <1% Placebo: <1% | 120 mg: <1% Placebo: <1% | 100 mg: <1% 300 mg: <1% Placebo: <1% |
Side effects: Injection site reactions | 70 mg: 6% 140 mg: 5% Placebo 3% | 675 mg quarterly: 18-19% 225 mg monthly: 23% Placebo: 4% | 120 mg: 18% Placebo: 13% | N/A |
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