On February 21, 2020, the Food and Drug Administration (FDA) approved VYEPTI (eptinezumab-jjmr) for use in the prevention of episodic and chronic Migraine attacks. Vyepti is an anti-CGRP (calcitonin gene-related peptide) monoclonal antibody – the fourth to be approved by the FDA.

Vyepti is the first anti-CGRP drug to be administered in a quarterly intravenous infusion.


Other drugs in this anti-CGRP category – Aimovig, Emgality, and Ajovy – are given monthly via self-injection at home. Vyepti is given in a quarterly infusion at the doctor’s office, which means you don’t have to think about migraine as often.

Clinical studies show treatment with eptinezumab can lead to fewer monthly Migraine days. Even better, studies also show that it begins working quickly and the benefits continue over time. The recommended dose is 100 mg every 3 months, although some may benefit from a dose of 300 mg ( ).

Vyepti is currently approved for adult use in the United States. The manufacturer Lundbeck, who acquired Alder Biopharmaceuticals in 2019, has submitted an application for market authorization in Canada and also plans to file in the European Union during 2020. They then plan to submit applications in other countries around the world, including China and Japan. We’ll keep you updated.

What does the approval of this new drug mean for people with Migraine? It represents a new option and new hope for less pain, fewer Migraine days, and more healthy days doing the things you love. Let’s break down what you need to know.

What is CGRP and How it Works in Migraine

Researchers suspect CGRP plays a key role in Migraine. This neuropeptide is released from trigeminal nerve fibers during a Migraine and causes vasodilation that results in neurogenic inflammation and pain. These pain impulses are transmitted along the trigeminovascular system and eventually to the higher cortical centers ( ).


Serum levels of CGRP have been found to be elevated during episodic and chronic Migraine attacks. In addition, when compared to individuals without Migraine, CGRP blood levels of patients with Migraine are elevated between attacks ( ).

Medications that target CGRP offer a disease-specific therapy that can help treat Migraine attacks in those with episodic or chronic Migraine.

Eptinezumab joins Emgality (galcanezumab), Ajovy (fremanezumab), and Aimovig (erenumab) as the fourth anti-CGRP drug on the market to prevent Migraine attacks.

The first acute medication that works by blocking CGRP, Ubrelvy (ubrogepant) was just approved by the FDA in December 2019. More acute meds in this ‘gepant’ category are expected to come on the market in the coming years.

Clinical Data Supporting Eptinezumab for Migraine Prevention

FDA approval of eptinezumab is based on the results of two global phase 3 clinical trials, PROMISE 1 and PROMISE 2. President and CEO of Alder Biopharmaceuticals, Bob Azelby explained: “We feel really good about the safety and efficacy data seen in the trials with great consistency between the trials ( ).”

Episodic Migraine


PROMISE 1 was a Phase 3 randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of eptinezumab for episodic Migraine prevention.

Patients were randomized and 888 received eptinezumab (300 mg, 100 mg or 30mg) or placebo, administered by infusion once every 12 weeks. The study met both primary and secondary endpoints, including ( ).

Reduction in monthly migraine days.

Patients with a baseline average of 8.6 headache days a month experienced a reduction of 4.3 monthly Migraine days for 300 mg (p=0.0001) and 3.9 days for 100 mg(p=0.0179) compared to an average 3.2 days for placebo.

Rapid Day 1 response

53.6% reduction in the proportion of patients experiencing Migraine on the day following administration at 300mg (p=0.0087, unadjusted)

51.3% reduction at 100mg (p=0.0167, unadjusted), compared to 20.7% for placebo

Significant 75% response rate (aka ‘Super-responders)

About one-third of patients achieved a ≥75% reduction in Migraine days through 4 and 12 weeks

Average of 1 in 5 patients had 100% response: no Migraine attacks in any given month, months 1 through 6

The safety profile was similar to placebo: consistent with previously reported eptinezumab studies.

Chronic Migraine

PROMISE 2 was a Phase 3, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of eptinezumab for chronic Migraine prevention. Patients that participated in the trial had an average of 16.1 Migraine days per month at baseline.

In the study, 1,072 patients were randomized and received either eptinezumab (300 mg or 100 mg) or placebo, administered by infusion once every 12 weeks. The main study findings include ( ).

Reductions in monthly Migraine days

a highly statistically significant reduction of 8.2 monthly Migraine days from baseline compared to 5.6 days for placebo (p<0.0001)

Rapid Day 1 response

52% reduction in Migraine risk beginning Day One post-infusion compared to 27% for placebo (p<0.0001)

Responder rates for months 1-3

61% achieved 50 percent or greater reduction in Migraine days from baseline compared to 39% for placebo (p<0.0001)

33% achieved a 75% or greater reduction in Migraine days from baseline, compared to 15 % for placebo, (p<0.0001)

15% had no Migraine attacks (i.e., 100 percent response) for a full three months, compared to 5 percent for placebo, p<0.0001 (post hoc, unadjusted)

Eptinezumab Shows Rapid Onset and Sustained Benefit

The number of participants who experienced an immediate benefit from eptinezumab in clinical trials was enough to impress neurologist and headache specialist Dr. Peter Goadsby who said,


“The new data demonstrate that eptinezumab administered via infusion delivers rapid onset and sustained benefit following one administration. Rapid onset of effect is a true paradigm shift in Migraine preventive treatment. I’m excited about the potential for my patients to experience early and meaningful periods of Migraine freedom.”

How is Eptinezumab Given?

Eptinezumab is the first CGRP therapy for Migraine to be administered intravenously.

Eptinezumab offers the convenience of an every 12-week intravenous infusion, which, according to Alder, allows for 100% of the dose to be available for selectively inhibiting CGRP ( ). The infusion takes about 30 minutes, according to the patient information provided by Lundbeck.

This is a great option for those who do not want to self -administer the drug with an autoinjector like with Emgality (galcanezumab), Ajovy (fremanezumab), and Aimovig (erenumab). However, Epintinezumab will require administration in an infusion center instead of at home.

Does Eptinezumab have side effects?

The most commonly reported side effects for eptinezumab in clinical trials, occurring at an incidence of 2.0% or greater, were nasopharyngitis (swelling of the nasal passages and the back of the throat) and hypersensitivity reactions (like flushing) ( )

When Will Eptinezumab Be Available?

Eptinezumab will be available for use in the United States this April ( ).

How much will Eptinezumab cost and will my insurance cover it?

We still don’t know how much it will cost and what kind of copay programs will be available. If the launch of similar new Migraine drugs has taught us anything, it’s that the new treatment will likely be costly and not covered in major insurance formularies.


We can expect Vyepti to cost around $6900 per year or $575 per month, which is the list price for competing CGRP treatments ( ). Those with government-funded insurance like Medicare, Medicaid, and TriCare will have the most difficulty accessing the drug, because they are excluded from discount co-pay programs offered by the manufacturer. We will keep you updated as soon as we know more.

Those with Chronic Migraine who receive quarterly Botox injections may also have a difficult time getting coverage. Although there is no medical reason that says you can’t use Botox and a CGRP mono-clonal antibody, insurance companies have been making people choose between the two treatments. Equal and affordable access to new treatments remains a huge advocacy issue for patient and physician groups.

More Migraine Drugs in the Pipeline

Thankfully, there are other options in the works for people with Migraine to find relief! CGRP has been making a lot of noise, but it’s not the only target for Migraine therapies in development. Lundbeck is investigating new monoclonal antibody therapy options, including ALD1910 which targets the protein pituitary adenylate cyclase-activating peptide or PACAP.

Alder (Lundbeck) explains that those who experience Migraines related to the release of PACAP, typically experience a slower onset of the attack with more symptoms of aura. Their investigational drug is said to target the ligand which will then bind to all 3 PACAP receptors, which in animal models reduced photophobia ( ).

Other trials are also currently underway evaluating drugs targeting PACAP so stay tuned. We will keep you posted!

The Take-Away

If you haven’t gotten the success you want in preventing Migraine attacks, do not lose hope! This exciting new development in Migraine prevention and the current FDA approval offer hope to many people with both episodic and chronic Migraine attacks.


Even if another monoclonal antibody – Aimovig, Ajovy, or Emgality – didn’t work as you wanted, Vyepti offers another chance for success. Headache specialist and Professor of Neurology at the Mayo Clinic Dr. David Dodick remains “cautiously optimistic” that patients who don’t respond to one monoclonal antibody may respond to another.

“Researchers still don’t know about the comparative effectiveness of the drugs, or if patients who don’t respond to one would respond to the other. If history tells us anything, it’s that different drugs within the same class can have a different effect in an individual patient,” said Dr. Dodick ( ).

Speak to your healthcare provider to see if eptinezumab is the right choice to prevent your Migraine attacks. Stay hopeful – a new, safe, and effective option will be available very soon!

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