The first medicine designed to prevent migraines was approved by the Food and Drug Administration on Thursday, ushering in what many experts believe will be a new era in treatment for people who suffer the most severe form of these headaches.
The drug, Aimovig, made by Amgen and Novartis, is a monthly injection with a device similar to an insulin pen. The list price will be $6,900 a year, and Amgen said the drug will be available to patients within a week.
Aimovig blocks a protein fragment, CGRP, that instigates and perpetuates migraines. Three other companies – Lilly, Teva and Alder – have similar medicines in the final stages of study or awaiting FDA approval.
“The drugs will have a huge impact,” said Dr. Amaal Starling, a neurologist and migraine specialist at the Mayo Clinic in Phoenix. “This is really an amazing time for my patient population and for general neurologists treating patients with migraine.”
Millions of people experience severe migraines so often that they are disabled and in despair. These drugs do not prevent all migraine attacks, but can make them less severe and can reduce their frequency by 50 per cent or more.
As a recent editorial in the journal JAMA put it, they are “progress, but not a panacea.”
Until now, drugs used to prevent migraines were designed to treat other diseases, like high blood pressure. They are not very effective, may work only temporarily, and often are laden with intolerable side effects.
In clinical trials, people taking the new drugs reported no more side effects than those taking a placebo. The side effects over the long term and among people with chronic diseases remain to be determined.
“For now, they look fantastic,” Dr. Stewart J. Tepper, a professor of neurology at Dartmouth College, said of the new drugs. “They shake the ground under our feet. They will change the way we treat migraine.”
Tepper and Starling, like most leading migraine specialists, have consulted with the drug companies and enrolled patients in their clinical trials.
One in 7 people worldwide experience migraines, among them 37 million Americans – as many as 20 per cent of women, and 10 per cent of men.
About 2 per cent of the global population copes with chronic migraines. By some estimates, migraine is the third most common disease in the world, and it ranks among the top 10 causes of disability.
It is not just a headache: A migraine often is accompanied by disabling symptoms like nausea and vomiting, difficulty speaking, and an aversion to light and noise. The headache can be throbbing and last for hours or days.
The new medicines are intended for the estimated 2.8 million Americans who have a migraine many times each month. Treating these people has been challenging, doctors say.
Patients often try the currently available treatments one after another, in varying combinations. Drug side effects are frequent and include mental fogginess, sedation, weight gain, sexual dysfunction and dry mouth leading to cavities.
Some patients find the side effects worse than the migraines. Eighty-five per cent of migraine patients stop taking the drugs within a year.
For a draft review of migraine drugs, the nonprofit Institute for Clinical and Economic Review surveyed patients with frequent migraines. Many said they did not make plans or commitments – even staying out of the workforce – because they never knew when they would get a migraine that could disable them for hours or days.
They were “frustrated, depressed, defeated, isolated,” the report said, or felt they were a burden to society. They complained of being stigmatized – their migraines were not taken seriously. They often tried a long list of treatments to little of no avail.
“It’s a pretty miserable situation,” Tepper said.
Even small children get migraines, said Dr. Andrew D. Hershey, chairman of neurology and director of the headache center at Cincinnati Children’s Hospital Medical Center. Recently, he saw a 2-year-old with migraines.
Hershey is involved in a clinical trial testing one of the new drugs in 12– to 17-year-olds and plans eventually to enroll children as young as 6.
But monoclonal antibodies like the new drugs are grown in living cells and expensive to produce. The high price of the Amgen drug raises questions about whether insurers will pay and whether patients with high copayments can afford the medicine.
In a preliminary analysis of cost-effectiveness, ICER concluded that if the Amgen drug cost $8,500 a year, the price would be reasonable for the expected improvement in quality of life for patients with a migraine at least 15 times a month and no other options, said Dr. David Rind, the institute’s chief medical officer.
The group will publish a final analysis in two weeks, incorporating public input and the actual price of Amgen’s drug.
The idea behind the new drugs dates to the 1980s, when researchers noticed that the protein fragment CGRP seemed to play a role in migraines. It transmits signals between nerves and also dilates blood vessels.
Over the years, researchers continued to gather evidence. “Information came in dribs and drabs over time,” said Dr. Sean E. Harper, executive vice president for research and development at Amgen.
Eventually, a fuller picture emerged: People who get migraines seem to make too much CGRP.
When investigators infused CGRP into people prone to migraines, they got headaches. When they gave the molecule to people who do not get migraines, it usually did not instigate one.
That was a pivotal finding, said Dr. Robert Conley, global development leader for migraine therapeutics at Lilly. It meant that blocking some but not all CGRP might prevent headaches without interfering with its normal functions in the body.
Companies began developing small molecules to block CGRP, but they turned out to be too toxic to use as drugs. So researchers turned to antibodies, which work differently. Aimovig, the newly approved drug, blocks the molecule on the cell surface that CGRP must attach to in order to work.
Antibodies persist in the body, Harper noted, which is why patients can be treated just once a month. (Unlike the other companies, Alder is developing a medicine to be infused intravenously in a doctor’s office every three months.)
Dr. Laura Greer, 38, a pediatrician in Etna, New Hampshire, has about eight migraine days a month despite using eight treatments, including a device that transmits a magnetic pulse to her head. Without them, her monthly migraine days numbered 14.
She tried over 40 treatments over a period of years to find a handful that helped. And she puts up with side effects like a dry mouth and forgetting words.
“I am just so hopeful about this new medication,” said Greer, who is one of Tepper’s patients. But she worries about its price and whether her insurer will pay.
Robin Overlock, 32, participated in a clinical trial of Teva’s CGRP inhibitor. She had been having 27 migraine days a month, with episodes that could last five days.
She did not know if she was getting the drug or a placebo, but once she began getting injections she felt she had many fewer migraine days.
When the study ended, she and the other participants received the active drug. Her last injection was in January.
Since then, she has had only two headaches. Both were so mild she did not need medication, and just one migraine lasted five hours.
“It’s definitely life-changing,” Overlock said.