Experts Say CGRP Drugs Are First-Line Therapies for Migraine Prevention

By Pat Anson, PNN Editor

Migraine medications that block calcitonin gene-related peptides (CGRPs) are “equal to or greater” than other migraine prevention drugs and should be considered first-line therapies, according to a new guideline from the American Headache Society (AHS).

It’s the first time the organization has endorsed CGRP inhibitors for migraine prevention, despite their high cost and limited availability due to insurance requirements. Many insurers have step-therapy policies that require patients to start with cheaper first-line treatments before trying other drugs.

"Moving CGRP-targeting therapies to the first line of treatment could have a transformational impact on the prevention of migraine attacks and their associated burdens," Andrew Charles, MD, AHS president and lead author of the guideline recently published in the journal Headache. 

CGRP inhibitors block a protein that binds to nerve receptors in the brain and trigger migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications for migraine prevention and/or treatment, the biggest innovation in migraine therapy in decades.   

Older drugs that have long been used for migraine prevention were originally developed for other conditions. They include amitriptyline, a tricyclic antidepressant; simvastatin, which is used to control cholesterol; topiramate (Topamax), an antiseizure medication; and beta-blockers commonly used to control blood pressure.  

The AHS says there is growing “real world” experience that CGRP inhibitors work better than the older, repurposed medications.

“The evidence for the efficacy, tolerability, and safety of CGRP-targeting migraine preventive therapies is substantial, and vastly exceeds that for any other preventive treatment approach,” the AHS said. “The data indicates that the efficacy and tolerability of CGRP-targeting therapies are equal to or greater than those of previous first-line therapies and that serious adverse events associated with CGRP-targeting therapies are rare.”

The biggest problem with CGRP inhibitors is their cost, which can reach tens of thousands of dollars a year. Eight doses of Nurtec, a tablet taken daily, cost over $1,000; while the listed price for Emgality is $706 for a self-injectable syringe used monthly. Prices will vary, depending on insurance and whether a patient qualifies for discounts or patient assistance programs.

By comparison, amitriptyline and simvastatin are bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets. A recent study suggests that amitriptyline and simvastatin work just as well as CGRP inhibitors in reducing the need for medications to treat migraine pain, an indication that they are effective at prevention.

Despite the disparity in cost, the AHS maintains the overall benefits of CGRP inhibitors may justify the price. There are substantial hidden costs to migraine attacks, which can result in lost productivity, income, education, and personal relationships.   

“We recognize that the CGRP-targeting preventive therapies are significantly more expensive on a yearly basis than most of the previously established therapies, and some argue that this expense is a primary consideration in clinical decision-making,” the AHS said. “On the other hand, we argue that it is critically important to consider not only the direct cost of the treatment but also the substantial costs to the individual and society if effective treatment is delayed.”

Migraine affects about 39 million people in the United States and 1.1 billion worldwide. In addition to headache pain, migraine can cause nausea, blurriness, and sensitivity to light or sound. Women are three times more likely to suffer from migraines than men.  

Why Women Are More Likely to Suffer Migraines

By Pat Anson, PNN Editor

German scientists may have finally proven a link between hormones and migraines, and why women suffer migraines at triple the rate that men do. In studies on animals and humans, researchers found that calcitonin gene-related peptides (CGRPs) increase in females during menstruation.

CGRP is a protein that binds to nerve receptors and dilates blood vessels in the brain, causing migraine pain. Several medications are now on the market that inhibit CGRP, one of the biggest innovations in migraine treatment in decades.

“This elevated level of CGRP following hormonal fluctuations could help to explain why migraine attacks are more likely during menstruation and why migraine attacks gradually decline after menopause,” says Bianca Raffaelli, MD, of Charité – Universitätsmedizin Berlin in Germany. “These results need to be confirmed with larger studies, but we’re hopeful that they will help us better understand the migraine process.”

Raffaelli and her colleagues measured CGRP levels in the blood and tear fluid of 180 women during their menstrual cycles, and found that those who suffer from episodic migraines had significantly higher concentrations of CGRP during menstruation, when estrogen levels are low.

“This means that when estrogen levels drop immediately before the start of a menstrual period, migraine patients release more CGRP,” said Raffaelli, lead author of a study published in the journal Neurology. “This could explain why these patients suffer more migraine attacks just before and during their monthly period.”

In women who take oral contraceptives, there were hardly any fluctuations in their estrogen or CGRP levels. The same was true for postmenopausal women.

“Taking birth control pills and the end of menopause do in fact bring relief for some female migraine patients. But as our study also shows, there are women who suffer from migraine even without any hormonal fluctuations. We suspect that other processes in the body play a role in triggering attacks in those patients. After all, CGRP isn’t the only inflammatory peptide that can cause a migraine attack,” said Raffaelli.

The study also suggests that measuring CGRP levels in tear fluid is feasible and warrants further investigation, because accurately measuring CGRP in the blood is challenging due to its short half-life.

The research team now plans to study how other physical processes are influenced by the menstrual cycle, such as blood vessels and brain function. They also plan to take a closer look at CGRP levels in men of varying age groups.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound.

New Test Predicts Effectiveness of CGRP Drugs for Migraine

By Pat Anson, PNN Editor

CGRP inhibitors have been one of the biggest innovations in migraine treatment in decades. CGRP stands for calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP inhibitors for migraine prevention and treatment.

The problem with anti-CGRP therapies – besides their high cost – is that they only work for about half the people who take them.

A new test may take some of the guesswork out of CGRP therapy, by predicting with about 80% accuracy which patients will respond to CGRP inhibitors before treatment begins.  In a small study published in the journal Cephalalgia, Harvard Medical School researchers found that most migraine patients with non-ictal cephalic allodynia -- pain sensitivity experienced in-between migraine attacks – did not respond to CGRP treatment. Conversely, most patients without non-ictal cephalic allodynia did respond to CGRP therapy.  

Determining which patients have or don’t have cephalic allodynia is relatively easy, through a novel Quantitative Sensory Testing (QST) algorithm that measures how sensitive patients are to heat, cold and being poked in the skin with a sharp object. The test identified CGRP responders with nearly 80% accuracy and non-responders with nearly 85% accuracy.

“Detection of non-ictal cutaneous allodynia with a simplified paradigm of QST may provide a quick, affordable, non-invasive, and patient-friendly way to prospectively distinguish between responders and non-responders to the prophylactic treatment of migraine with drugs that reduce CGRP signaling,” wrote lead author Rami Burstein, MD, Professor of Anesthesia, Harvard Medical School.

Burstein helped develop the QST test in collaboration with CGRP Diagnostics. The test can be done in about five minutes in a doctor’s office.

“This is all about improving outcomes for people suffering from migraines and so we strongly recommend that all potential anti-CGRP recipients have the test done prior to prescription,” said Mark Hasleton, PhD, CEO of CGRP Diagnostics. 

“This will help provide migraine sufferers with either the best chance for treatment success for likely responders, or to enable rapid transition for likely non-responders to other treatment strategies, thus avoiding the misery of treatment failure. CGRP Diagnostics is currently in discussions with multiple key pharma and payor players in this area, with the expectation that such a test will become a prerequisite prior to anti-CGRP prescription.”

A surprise finding from the study is that cutaneous allodynia may be related to genetic factors that cause pain sensitivity, rather than the frequency or severity of migraines.

“This study unveils the mechanism of physiological response to anti-CGRP therapy and could fundamentally change the anti-CGRP therapy field,” said Iris Grossman, PhD, Founding Scientific Advisor at CGRP Diagnostics. “We now have an objective tool to tailor early and effective therapy to migraine sufferers. This novel test holds the potential for earlier access to anti-CGRP therapy, reduced need for prior treatment failures with generics, and enhanced formulary access. It also enables non-responders to rapidly transition to other treatment strategies, preventing a great deal of suffering and frustration for all.”

A 2020 survey of migraine patients by Health Union found that 52% of those who tried a CGRP therapy switched brands because the treatment didn’t work or because they didn’t like the side effects, such as constipation and weight gain.

CGRP medications are not cheap. Eight doses of Nurtec, the migraine treatment endorsed by Khloe Kardashian, can cost over $1,000 without insurance.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

FDA Approves Another Expensive Migraine Drug

By Pat Anson, PNN Editor

The highly competitive and lucrative market for migraine drugs will grow more crowded this month when AbbVie introduces Qulipta (atogepant), an oral CGRP medication developed for the prevention of episodic migraines.

The Food and Drug Administration approved Qulipta after seeing the results of a Phase 3 clinical trial that found the drug was 50 to 100% effective in preventing migraines.

"During the trial while taking Qulipta, I had many fewer migraine days. For the first time ever, I don't have difficulty doing my daily activities and I don't have to worry as much that a migraine attack will cause me to miss important events with family and friends," said Kelsi Owens, a trial participant who has lived with migraine for nearly three decades.

Like other CGRP inhibitors, Qulipta blocks proteins called calcitonin gene-related peptides from binding to nerve receptors in the brain and causing migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications, most of which are injected monthly.

Qulipta is a pill meant to be taken daily that comes in three different doses. Like other CGRP inhibitors, Qulipta is expensive. The wholesale price for a patient without insurance is $991 for 30 pills, according to Abbvie. Insured patients or those enrolled in an AbbVie patient support program will pay less.     

"Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients," said study investigator Peter Goadsby, MD, a neurologist and professor at University of California, Los Angeles. “I'm particularly encouraged by the convenience of the oral daily use of Qulipta, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates.”   

Qulipta is expected to compete directly with Nurtec, an oral CGRP inhibitor made by Biohaven Pharmaceuticals that is approved for both migraine prevention and treatment. A supply of eight Nurtec tablets costs about $941, depending on insurance coverage. Since it was introduced in 2020, Nurtec has generated about $200 million in revenue for Biohaven, with over 750,000 prescriptions filled.

AbbVie says Qulipta will be available in early October. Wall Street analysts project Qulipta sales will reach $1 billion by 2030.

Side effects from Qulipta include nausea, constipation, fatigue and loss of appetite. AbbVie is currently conducting a clinical trial to seek if Qulipta should also be approved for the prevention of chronic migraine – patients who have 15 or more headaches per month.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

UK Migraine Sufferers Face ‘Broken Healthcare System’

By Pat Anson, PNN Editor

The United Kingdom has a “broken healthcare system” that leaves millions of migraine sufferers without treatment or a proper diagnosis, according to a new study.

The report by The Migraine Trust estimates that one in every seven people in the UK – about ten million -- suffer from migraine attacks. Most say they haven’t been officially diagnosed by a doctor and have never seen a headache specialist.

Those who have been diagnosed often have trouble getting a new class of drugs to prevent migraine -- calcitonin gene-related peptide (CGRP) inhibitors – even though the medications have been approved for use by the UK’s National Health Service (NHS).

“My migraine has never been managed properly by the NHS. I’ve suffered for 13 years and they’ve increasingly become worse each year. I’m bed bound at least once a week,” a migraine sufferer told the charity. “I visit my GP regularly and they send me away with a different drug to try for another year before I can be considered for another. I asked for a referral to the migraine clinic and was refused by my doctor.”

The Migraine Trust filed Freedom of Information requests with nearly a hundred NHS healthcare systems in England, Northern Ireland, Scotland and Wales and found that only a few were giving eligible patients access to CGRP treatment.

“There is clearly a postcode lottery of care where only the lucky few can access a treatment which has proven transformational for many migraine patients,” Rob Music, CEO of The Migraine Trust, said in a statement. “This should be such an exciting and positive time for those needing migraine care, but right now this lack of access is leading to continued poor health and deep frustration.” 

CGRP inhibitors have been available in the United States since 2018, including a drug recently approved for both migraine prevention and treatment. The medications – which block a protein released during migraine attacks from binding to nerve receptors in the brain – are not cheap. Eight tablets of Nurtec, for example, cost nearly $1,000. 

Not treating migraines can be costly as well. The Migraine Trust estimates that lack of adequate migraine treatment in the UK results in 16,500 emergency admissions and 43 million lost workdays every year.  

The charity says migraine attacks also have a negative impact on the lives of migraine sufferers. In surveys, nearly a third said migraines negatively affect their mental and physical health. About one in four said migraines disrupt their family and social life. 

The pandemic has also taken a toll on migraine patients, with 68% saying their symptoms have worsened. Some reported it was because of stress, some because their lifestyle was harder to manage, and others because they couldn’t access the treatment they had been receiving. An increase in computer screen time during the pandemic also contributed to worsening migraine attacks.    

The Migraine Trust recommends that everyone seeing a doctor for head pain should be assessed for migraine and receive an individualized care plan. More headache specialists and neurologists should also be recruited to bring the UK in line with other European nations. The Trust called for public awareness campaigns to improve understanding of migraine symptoms and reduce the stigma associated with migraine. 

About a billion people worldwide suffer from migraine headaches, which affect three times as many women as men. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound.

FDA Approves First Drug for Both Migraine Treatment and Prevention

By Pat Anson, PNN Editor

Migraine sufferers have a new medication that not only treats migraines, but can also be used to help prevent them. Biohaven Pharmaceuticals announced this week that Nurtec (rimegepant) -- a drug already being used to treat migraine pain – has been approved by the FDA as a migraine preventative, making it the first migraine medication that can be used for both treatment and prevention.

Nurtec is a calcitonin gene-related peptide (CGRP) inhibitor, a relatively new class of medication that blocks a protein released during migraine attacks from binding to nerve receptors in the brain. Since 2018, the FDA has approved a handful of CGRP medications, most which are taken by injection.

Nurtec is a quick-dissolving tablet that is taken orally. A single dose can treat migraine pain for up to 48 hours. The expanded FDA approval means Nurtec can now also be taken daily or every other day to help reduce the frequency of migraines. 

“The FDA approval of Nurtec ODT for the preventive treatment of migraine -- along with its acute treatment indication -- is one of the most groundbreaking things to happen to migraine treatment in my 40 years of practicing headache medicine. To have one medication patients can use to treat and prevent migraine will likely change the treatment paradigm for many of the millions of people who live with migraine," said Peter Goadsby, MD, a Professor of Neurology at the University of California, Los Angeles.

Goadsby was one of the investigators in a Phase 3 study that helped prove Nurtec can be used as a migraine preventive. In findings recently published in The Lancet, Nurtec reduced the number of migraine days per month by 30% after one week of treatment. After three months of treatment, about half of the patients taking Nurtec had at least a 50% reduction in the number of moderate-to-severe migraine days per month.

Nurtec was well-tolerated by most patients during the clinical trial. Some reported nausea, stomach pain and indigestion.

"This FDA approval marks the beginning of a new era for migraine treatments, allowing the potential for healthcare professionals to prescribe, and patients to have, a single medication to treat and prevent migraine attacks,” Biohaven CEO Vlad Coric, MD, said in a statement. “This groundbreaking approach to treating the full spectrum of migraine disease, from acute therapy to prevention, can have a significant impact in a patient's life by helping to decrease treatment plan complexity and reduce challenges with adherence and polypharmacy.”

One obstacle to using Nurtec is its cost. Currently, a single 75mg tablet is priced at about $117. A supply of eight tablets is around $941, depending on your insurance coverage and pharmacy.  Biohaven has a patient assistance program that can help some patients who lack insurance or can’t afford the drug.

A recent survey of nearly 4,700 migraine patients by Health Union found that about one in four (26%) are currently using a preventive CGRP medication. About 11 percent said they were using a CGRP to treat migraine pain. Patients who did not try the drugs said they were concerned about side effects, long-term safety and their cost.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

Nearly 80% of People Taking New Migraine Prevention Drugs Report Improvement

By Pat Anson, PNN Editor

Nearly 80% of people taking a new class of medication to prevent migraine say their migraine headaches are “better” since they started taking the drugs, according to a survey conducted by Eli Lilly.

Calcitonin gene-related peptide (CGRP) inhibitors prevent migraines by blocking a key protein released during migraine attacks from binding to nerve receptors in the brain. Since 2018, the FDA has approved three injectable CGRP inhibitors and one oral CGRP medication for migraine prevention. Eli Lilly makes Emgality (galcanezumab), one of the monthly self-injected drugs.

Nearly 600 migraine patients who use CGRP inhibitors participated in the survey, which is part of Lilly’s OVERCOME study, a large web-based survey of migraine sufferers.

While 79.2% said their migraine was better, nearly 10% said it was worse and about 11% said there was no change. The findings were relatively consistent between patients who suffer a handful of migraines each month and those who have them more frequently.

"It is very encouraging that nearly 4 out of 5 people in the survey taking a CGRP monoclonal antibody felt better and reported their migraine had improved," Sait Ashina, MD, a neurologist and scientific advisor to the OVERCOME study, said in a statement.

"It is also notable that the OVERCOME survey reported the clinically meaningful distinction between individuals who reported no change in their migraine with those who said their migraine worsened. This distinction can enhance conversations between the healthcare provider and the patient regarding treatment expectations when considering the use of these novel migraine preventive medications."

Nearly two-thirds (62.6%) of those who used a CGRP inhibitor said they also took another migraine prevention drug, such as topiramate and duloxetine. Use of an additional medication was generally higher among patients who reported frequent migraines.

Lilly presented the survey results this week at the 18th Migraine Trust International Symposium.

The findings are similar to those in a 2019 survey of migraine patients conducted by Health Union. Over half of those using CGRP inhibitors said the benefits of taking the drugs outweighed their side effects. About 9 percent said the medications were not worth the side effects, which include constipation, fatigue and weight gain.

The Health Union survey also found that patients who were not satisfied with a CGRP medication wasted little time switching to a new brand. Most of those who switched said the drugs did not work or stopped working after an initial period of efficacy. 

FDA Approves First Intravenous Preventive Treatment for Migraine

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved the first intravenous treatment for the prevention of migraine in adults, adding to an increasingly crowded field in new migraine drugs.

Lundbeck, a Danish pharmaceutical company, said Vyepti (eptinezumab-jjmr) would be available in April 2020. The recommended dose is 100 mg every 3 months; although some patients may benefit from a dose of 300 mg. Price details were not released.

Vyepti is a humanized monoclonal antibody that prevents migraines by blocking a key protein — calcitonin gene-related peptides (CGRP) -- from binding to nerve receptors in the brain.

Since 2018, the FDA has approved three injectable CGRP inhibitors for migraine prevention and recently approved the first oral tablet for migraine treatment. Vypeti is the first CGRP blocker to be administered intravenously.

“With the approval of Vyepti, I am pleased that we are now able to offer a new IV therapy that achieves the key treatment goal of preventing migraine over time while also delivering on the need for earlier onset of efficacy,” Dr. Deborah Dunsire, President and CEO of Lundbeck, said in a statement.

The efficacy and safety of Vyepti was demonstrated in two phase III clinical trials (PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine) involving over 1,700 patients. Treatment benefit was observed for both doses of Vyepti as early as one day after infusion, and there was a sustained reduction of migraines through the second dose.

“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75 percent and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Dr. Peter Goadsby, a professor of neurology at King’s College, London and the University of California, San Francisco. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”

Patients were allowed to continue using other migraine or headache medications during the trials. About 2 percent of patients treated with Vyepti discontinued treatment due to adverse reactions, such as an upper respiratory infection and hypersensitivity that causes facial flushing and rash.

Lundbeck has submitted an application for market authorization of Vyepti in Canada and plans to file in the European Union during 2020, followed by the submission of drug applications in other countries around the world, including China and Japan.

Migraine affects about a billion people worldwide and 36 million adults in the United States, according to the American Migraine Foundation. It affects three times as many women as men. In addition to headache pain, migraine can also cause nausea, vomiting, blurriness or visual disturbances, and sensitivity to light and sound.