Head-to-Head Migraine Study Ends in Tie

By Pat Anson, PNN Editor

An unusual head-to-head competition between two migraine prevention drugs has ended in a virtual tie. There were no substantial differences in effectiveness between Emgality and Nurtec, according to preliminary results from a clinical trial released by Eli Lilly, the maker of Emgality.

Emgality and Nurtec both inhibit calcitonin gene-related peptides (CGRP), a protein that causes migraine pain, but their delivery systems are different. Emgality is injected once a month, while Nurtec is an oral medication taken every other day made by Biohaven Pharamceuticals, a subsidiary of Pfizer.

Eli Lilly launched the trial in late 2021, enrolling 575 participants in a Phase 4, double-blind, placebo-controlled study evaluating the efficacy and safety of Emgality (galcanezumab) and Nurtec (rimegepant) for 3 months in adults with episodic migraine.

The so-called CHALLENGE-MIG trial was a bold and somewhat risky move by Lilly, as it seeks to gain more market share in the highly competitive $2 billion U.S. migraine market.

In a statement, Lilly said Emgality did not meet the study's primary goal, which was statistical superiority to Nurtec in achieving at least a 50% reduction in monthly migraine headache days. The response rates of patients and safety profiles of both drugs were similar.

Lilly said Emgality was superior to Nurtec in some secondary outcomes, but didn’t disclose what they were. The company would only say that Emgality helped prevent migraines, as it has in previous studies.  

"These results bolster our knowledge of Emgality's ability to work quickly and help patients improve their quality of life with less frequent dosing," Anne White, executive vice president of Eli Lilly, said in a press release. "Reducing the frequency of migraine headache days can help people experience more freedom from the burden of this debilitating neurological disease and get back to participating in the daily activities that matter most to them."

Final result from the CHALLENGE-MIG trial won’t be posted until later this year.

“Nurtec ODT is the first and only medication approved as both an acute treatment for migraine and a preventive treatment for episodic migraine in adults. It offers flexibility to patients in treating their migraines and is the leading prescribed oral CGRP receptor antagonist,” Pfizer said in a statement. “We are confident in the efficacy and tolerability profile of Nurtec ODT as demonstrated in the clinical trials and the well-established patient preference for oral agents over injectables.

First approved by the FDA in 2018, CGRP inhibitors are the biggest innovation in migraine treatment in decades. They are also expensive, whether taken by pill or injection.

The listed cash price for Emgality is $679 for a single injection or $8,148 annually; while 8 tablets of Nurtec cost $1,011 or about $23,000 a year. Costs to patients will vary, depending on insurance coverage, copay assistance programs and rebates.

Unusual Head-to-Head Migraine Study Pits Emgality vs. Nurtec

By Pat Anson, PNN Editor

Competition has grown intense between pharmaceutical companies in the $2 billion U.S. migraine market.

You’ve probably seen their TV commercials. Eli Lilly hired Olympic athletes to pitch Emgality, an injectable migraine preventative, while reality star Khloé Kardashian is appearing in commercials for Nurtec, an oral medication made by Biohaven Pharamceuticals

Lilly is now taking the competition a step further, with an unusual head-to-head clinical study – rare in the pharmaceutical industry – that pits Emgality against Nurtec. The company is enrolling 700 adults with episodic migraine in a randomized, double-blind, placebo-controlled trial. The so-called CHALLENGE-MIG study will directly compare the efficacy and safety of the two drugs.

“Lilly’s CHALLENGE-MIG study will help us understand how different types of preventive medications may help people achieve the goals that matter most to them. It’s exciting that insights generated in this first-of-its-kind head-to-head trial will be able to spark treatment plan discussions between people with migraine and their health care providers,” Shivang Joshi, MD, a trial investigator at Dent Neurologic Institute, said in a Lilly press release.

Emgality and Nurtec both inhibit calcitonin gene-related peptides (CGRP), a protein that causes migraine pain, but their delivery systems are very different. Emgality is injected once a month, while Nurtec is taken in a pill every other day.

Emgality was one of the first CGRP inhibitors to be approved by the FDA in 2018, while Nurtec is a relative newcomer, first approved in 2020. Nurtec’s label was recently expanded to include both migraine prevention and treatment.

The primary goal of the Lilly study is to see which drug gives patients a greater reduction in monthly headache days, with a secondary goal of measuring quality of life improvements.

“We believe patients should expect more and get more from medications that can help prevent migraine. Therefore, we look forward to sharing the findings from our Emgality versus Nurtec ODT head-to-head trial,” said Anne White, senior vice president of Eli Lilly and president of Lilly Neuroscience.

Biohaven’s CEO welcomes the study and sees it as an affirmation of Nurtec’s growing share of the market. Since it was introduced last year, Nurtec has generated about $200 million in revenue for Biohaven, with over 750,000 prescriptions filled. 

"This new head-to-head trial affirms that Nurtec ODT is perceived as the new standard of care.  The dual-therapy action of Nurtec ODT is unique and provides clear advantages to both treat and prevent migraine attacks.  Since the launch of oral acute CGRP agents, the performance of injectable CGRP (inhibitors) is now negligible to flat,” Vlad Coric, MD, CEO of Biohaven Pharmaceuticals, said in a statement to PNN. 

“Regardless of this Emgality study outcome, the Nurtec ODT value proposition will not be matched. And Nurtec ODT will have an impressive and entrenched market penetration by the completion of the proposed head-to-head study.  We continue to hear from patients, who want oral over needle-based therapies.” 

Regardless of whether it’s a pill or injection, both drugs are expensive. A supply of eight Nurtec tablets costs about $941, depending on insurance coverage. The listed price for Emgality is $627 for a single injection or about $7,524 annually.

If you’d like to know more about the study or possibly enroll in it, call the Lilly Answers Center at 1-800-545-5979.

Survey Finds Patients Wary of Trying CGRP Migraine Drugs

By Pat Anson, PNN Editor

Khloe Kardashian and Serena Williams have their work cut out for them. Despite their endorsement of a new type of migraine medication, many patients remain wary of the drugs and few have tried them, according to a large new survey.

The annual survey of nearly 4,700 migraine patients by Health Union found that about one in four (26%) are currently using a preventive CGRP medication, down from 29% in last year’s survey. And only 11 percent of patients said they were using a CGRP to treat migraine pain.

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 four injectable CGRP inhibitors (Aimovig, Ajovy, Emgality, Vyepti) to prevent migraine and two CGRP tablets for acute migraine (Ubrelvy, Nurtec). The latter two were recently endorsed by reality star Kardashian and tennis star Williams.   

Although Eli Lilly, Teva, Amgen, and other drug companies have aggressively marketed CGRP medications and even given the drugs away for free to get people to try them, sales growth has been slow. Only Aimovig and Emgality are used by at least 10 percent of migraine patients.

PERCENTAGE OF PATIENTS CURRENTLY USING CGRP INHIBITORS

SOURCE: HEALTH UNION 'MIGRAINE IN AMERICA 2020'

Most migraine patients continue to rely on older and cheaper medications such as triptans, anti-depressants, anti-convulsants, over-the-counter drugs, and Botox injections.

The Health Union survey helps explain why. While most patients are aware of CGRP inhibitors and nearly half (43%) had tried a preventive CGRP, most stopped taking them after trying just one brand. That’s not uncommon for migraine sufferers, who often have try multiple treatments before finding one that works.   

“Everybody’s experience with treatment is different. And the fact that there are multiple brands available is actually a really good thing. Because some of them just happen to work better for some people than others,” says Brian Green, Health Union’s vice-president of community business solutions.

CGRP’s do work for some patients. The Health Union survey found that 58% of patients currently using a preventive CGRP reported having less head pain. And nearly half said they didn’t react as strongly to migraine triggers such as loud noises and bright light.  

Those who had heard of preventive CGRP medications but had not tried them cited a number of reasons:

• 44% Doctor has not recommended it

• 27% Concerned about side effects

• 21% Concerned about long-term safety

• 19% Can’t afford them

• 14% Insurance won’t cover

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

Nearly half the patients surveyed said they were still using triptans or over-the-counter pain medication for migraine relief. Antidepressants and Topamax were the most commonly used medications for migraine prevention. 

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. 

New Migraine Prevention Drugs Making Inroads

By Pat Anson, PNN Editor

Over half the patients taking a new class of medication designed to prevent migraines say the benefits of treatment outweigh the drugs’ side effects, according to a new survey.

The drugs prevent migraines by blocking a 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.

Although the drugs are still relatively new, a recent survey of over 4,700 migraine patients by Health Union found that about a third (29%) are currently using a CGRP medication, while 12% had used one in the past.

Most said the drugs were effective at migraine prevention and worth the side effects, which include constipation, fatigue and weight gain. Only 9 percent said the drugs were not worth the side effects.

“CGRPs are in many ways a treatment revolution,” says Brian Green, vice-president of community development for Health Union. “There has not been a new class of medication specifically designed for treatment of migraine for decades. So this really is groundbreaking.” 

Green said patients with chronic severe migraine are more likely to be early adopters of CGRP therapy, as opposed to people who have episodic migraines and fewer attacks.   

Patients on CGRP therapy were more likely to say their migraine attacks increased over time and that they experience a wide array of symptoms, including head pain, brain fog, difficulty concentrating, fatigue, loss of words, memory loss and sensitivity to touch. 

“Their symptoms are so severe they want the first available new treatment,” Green told PNN. 

But the early adopters were also more impatient. Health Union’s survey found that patients who were not satisfied with a CGRP inhibitor wasted little time switching to a new brand. About 40% waited less than a month and 43% waited up to 3 months. Most of those who switched said the drugs did not work or stopped working after an initial period of efficacy. 

The three CGRP inhibitors currently on the market are Aimovig, Ajovy, and Emgality, which are taken by injection about once a month. The first oral CGRP for migraine treatment, Ubrelvy, was approved by the FDA last month and is expected to be available in the next few weeks.  

Most patients surveyed by Health Union said they would prefer taking a daily CGRP pill as opposed to a monthly injection.  

Constipation was the leading side effect reported by patients getting CGRP injections. Nearly a third said the drugs made them constipated, while others complained of reaction at the injection site (16%), fatigue (15%), weight gain (12%) and dry mouth (11%). 

About half the patients surveyed said they were still using a triptan or over-the-counter pain medication for migraine relief. Antidepressants and Topamax were the most commonly used medications for migraine prevention. 

Regardless of the drugs used, only 12% of patients said their migraines were well controlled under their current treatment plan.  

FDA Approves Third Injectable Migraine Drug

By Pat Anson, PNN Editor

Migraine sufferers will soon have another treatment option. Eli Lilly has announced that the U.S. Food and Drug Administration has approved Emgality (galcanezumab), a monthly self-injected drug for the prevention of migraine in adults.

Emgality is the third injectable migraine drug the FDA has approved this year. In May, the agency gave approval to Amgen’s Aimovig (erenumab), the first migraine drug that uses fully human monoclonal antibodies to target receptors in the brain where migraines are thought to originate.  Last week, the FDA approved Teva’s Ajovy, a migraine prevention drug that can be injected monthly or quarterly.

Lilly said the efficacy and safety of Emgality was demonstrated in three Phase 3 clinical trials in patients with episodic or chronic migraine.

Emgality reduced the number of monthly migraine headache days by an average of 4.7 days in patients with episodic migraine and by 4.8 days in patients with chronic migraine.  

Migraine affects a billion people worldwide and about 36 million adults in the United States, according to the American Migraine Foundation. In addition to headache pain and nausea, migraine can cause vomiting, blurriness or visual disturbances, as well as sensitivity to light and sound. Women are three times more likely to suffer from migraine than men.

“Despite the devastating impact of migraine, only about 10 percent of people living with the disease are currently taking a preventive treatment,” Christi Shaw, president of Lilly Bio-Medicines, said in a statement. “With this approval, we are thrilled to offer a preventive treatment option to adults living with this disease.”

Lilly said Emgality would be available “shortly” at a listed price of $575 for a single injection or $6,900 annually. That introductory price is identical to that of Aimovig and Ajovy, although various discounts or rebates could make the cost lower. Lilly said it would offer Emgality for up to 12 months free to patients with commercial insurance under its patient assistance program.   

“We know the impact high deductible and rising out-of-pocket costs have on families, and Lilly takes seriously our role in ensuring affordable access to Emgality for as many patients as possible,” said Shaw.

Earlier this month, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use issued a positive opinion of Emgality for the prevention of migraine in adults who have at least four migraine days per month. That positive opinion was referred for final action to the European Commission, which grants drug approval in the European Union.