It often starts with the aura.

Zig-zagging lines come into view, everyday light becomes searingly bright, and vision starts to slip. These are signals that a debilitating migraine is on its way.

“It’s like you’re possessed,” said Lorie Novak, who has suffered from chronic migraines since childhood. “I almost feel separate from my body, like it’s just this painful shell around me that’s not me.”

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Novak, now in her 60s, is one of the roughly 35 million Americans who suffer from migraines. There are few effective treatments, and no new drugs have been developed since the early 1990s.

But that could soon change. A handful of drug companies are pressing ahead with novel injectable therapies for migraines, chasing a blockbuster market that Wall Street analysts say could reach $8 billion a year in worldwide sales.

The new drugs target a bodily protein called CGRP, which plays a role in the dilation of blood vessels in the brain. Scientists haven’t nailed down just how the protein affects migraines, but they’re sure about two things: CGRP levels rocket up when headaches attack and normalize when they go away.

And thus four drug makers — Amgen, Eli Lilly, Teva Pharmaceuticals, and Alder Biopharmaceuticals — have fashioned antibodies that can bind to CGRP molecules and block their activity. The goal: to relieve the scourge of chronic migraines by stopping CGRP in its tracks.

So far, it seems to be working. In mid-stage clinical trials, each of the four treatments has eased symptoms for about half of study participants, cutting the number of days they’re afflicted by migraines roughly in half. It’s by no means a cure for migraines, but it should be enough to merit Food and Drug Administration approvals if the companies can replicate those results in larger trials, according to Eric Schmidt, a securities analyst at Cowen and Co.

Each treatment is now in late-stage development, targeting the roughly 38 percent of migraine sufferers who, like Novak, have at least four headache days per month. The first therapy could hit the market in 2018, and, if everything works out, all four could available by the end of the decade.

So far, the four drugs have performed similarly in clinical trials, and analysts expect the contenders will have to compete on price to grab market share.

“There will certainly be hypercompetition,” said William Ratner, Lilly’s senior director of global headache marketing. But the companies’ fortunes are intertwined, he said, and “the class only wins if headache care in America improves.”

Aiming to prevent migraines before they start

There’s plenty of room for improvement. Existing therapies are plagued by inconsistent efficacy and troublesome side effects, and patients are often left to rely on a repurposed treatment for epilepsy. That medication, Topamax, has been dubbed dubbed “Sleepomax” by doctors and patients because it’s also a heavy sedative.

“I’m very enthusiastic, as I think everyone in the field is, about having another treatment option for people with migraines,” said Dr. Elizabeth Loder, a professor of neurology at Harvard Medical School and chief of the headache division in the department of neurology at Brigham and Women’s Hospital.

Targeting CGRP is not a particularly new idea. Researchers picked up on the protein’s scent more than 30 years ago, and drug companies spent years trying to craft pills that might block its activity. Merck got all the way into late-stage trials with an anti-CGRP tablet, spending more than $1 billion only to find in 2011 that the drug had toxic effects on the liver and thus no future.

With the “exquisite sensitivity” of an antibody, however, scientists believe they can block CGRP without triggering dangerous side effects, Alder CEO Randy Schatzman said.

Because antibodies stay active in the body for weeks, the drug companies see their new products as preventative therapies, injected monthly or quarterly to keep headaches at bay. (Merck’s failed pill, by contrast, was meant as an on-the-spot treatment after the pain started.)

“So in some senses, it’s a paradigm shift,” Schatzman said.

But there are still hurdles to clear. Only about half of patients seem to respond to CGRP antibodies, and the companies have no way of predicting who they are ahead of time. A genetic test would be “the Holy Grail of personalized medicine,” said Rob Lenz, Amgen’s global development lead for neuroscience, but no one has made one yet.

And long-term safety remains a major question mark. To date, none of the companies has reported serious side effects in clinical trials, but they’ve only reported data from 12-week studies on about 1,500 total patients. It will take years to determine just what the new therapies do to the body over time, Loder said.

‘I felt like my life was being stolen from me’

Any advance, even an incremental one, would be a major leap for the field, said Emily Bates, who studies the genetic causes of headaches at the University of Colorado and is not affiliated with any of the companies working on migraine treatment.

Bates struggled with chronic migraines in high school and college. Like many patients, she didn’t respond to any of the preventative therapies available.

“The pain is more than anything I’ve ever experienced, and I’ve run on broken legs before,” she said. “I felt like my life was being stolen from me.”

Collectively, Americans miss about 113 million workdays each year because of migraine. That lost productivity costs society about $13 billion each year, according to the Migraine Research Foundation.

Yet scientific progress has been slow, in part because migraine was long considered a psychosomatic condition not worthy of serious research funding, Bates said.

It’s a “subjective symptom that predominantly affects women,” said Loder, the Harvard neurologist. “That’s a perfect combination of things that make people feel able to dismiss it.”

Novak, a professor of photography at New York University’s Tisch School of the Arts, spent years trying to hide her migraines because of the stigma attached to the condition. But she decided to change all that in 2009 with a project called Migraine Register. She takes a photo of herself each day she has a migraine. Some years, that’s more than 120 pictures.

The idea, in part, was to humanize chronic migraines. But the project also forced Novak to reckon with the toll of the disease, something she had tried to ignore for years.

“That for me was like a concrete proof of how it really does affect my life,” Novak said, “of how much time I lose.”

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  • Like the quote ” I felt like my life was being stolen from me”. Accurate. Friend told me yesterday, again, to drink water. TBI/epilepsy since 1 night of domestic violence! Cracked skull bones. I used Magnesium prn. Safe- stop if diarrhea occurs. Rx of Tegretol, and Percocet that sometimes helps.

  • First off aura is rare, occurring in less than 15% of patients, so migraines don’t “often” start that way.

    Second, why no mention of Botox? It’s the only FDA-approved treatment for chronic migraine and works great. There are many options aside from topamax (which is called “dopamax” because it makes you dumb, not sleepy –who are your sources?!)

  • I (male/64) started suffering with migraines around the age of eight. Doctors said kids don’t get migraines, so they ran an EEG (etc.) looking for tumors–nothing. (Adult description: IF I could pop an eyeball out and get my fingers about one inch inside my skull, I could grab the SPECIFIC nerve/vessel and rip the thing out = pain gone!) Later, drug therapy included ergots, depressants, and more over-the-counter crap than I would care to admit–nothing worked, save sleep. Many days have been wasted due to debilitating pain.
    Fast forward to age 40. Trying to keep up with full time work and a 12 hour college load, I could not afford down time. Thought to try something new–booked appointment with an anesthesiologist to discuss problem. RADICAL IDEA–“…have you tried a beta-blocker?”
    What?
    Forty plus years of pain and NOW I hear of this heretical drug? “Sign me up for trial. Let’s start with a handful!”
    MIRACLE CURE! Over the course of approximately six weeks we kept diminishing the dose, starting with 120 mg (too much) down to 40 mg per day–I understand this to be almost a threshold dose at my current 200 pounds. BUT IT WORKS! I estimate I averaged between four and six strong headaches a month (pre-beta blocker) down to my current two/three MILD…GENTLE headaches a year–easily staved off with aspirin. Daily meds is 40 mg of stuff called “Propranolol” (brand-name). I’ll be 65 in a couple of months; migraines are a burden I carried a long time ago! (I still don’t think anyone understands why or how it works–at least in people like me.)

    Note: Of all the wonderful substances man has available for various kinds of intoxication, ONLY THE DRUG ALCOHOL produces debilitating effects in me (migraines). My parents could drink–and get up the next day and smile; not me. Ergo, I do not drink. Alcohol is the ONLY food/substance/drug that I avoid. Hope this helps someone–migraines are terrible!

  • Try treximet… get a script from your doctor. I had horrible migraines, tried many different pills and nothing worked. Then I tried treximet and it essentially cured me. 20 minutes after I take it migrane is gone…. I never leave comments, but maybe I will help change one of your lives like the person who told me about treximet changed mine. You will be amazed it actually works…

  • I read an article that the vibrator was developed because back in the 1920s, the doctors recommended an orgasm. The doctor’s fingers would get tired so, the vibrator came about. Maybe it is time to back to simpler times.

  • Instead of drug companies focusing on coming up with more chemicals to put in your body and pocket the profit, they should be researching healthy organic eating. How about changing your diet, No dairy, gluten, artificial sweeteners, meat. Whole real foods and good old exercise and yoga. I was a sufferer of migraines for years, tool Advil, alleve, muscle relaxers, you name it. I tried it. Once I started to change my diet and practice yoga, decreases migraine headaches significantly.

    • Please. Don’t insult us with your nonsense. Do you not think migraine sufferers have tried everything already? Did you read the description of the pain? If it was as simple as following your garbage thinking of “expensive vegetables and meat cure everything” there wouldn’t be a problem. Honestly I could scream when someone spouts this kind of idiocy. Have you tried drinking more water? YES THANKS

    • What difference does it make? They are versions of the same word. I am interested in learning about preventing migraine, and I am not worried about choice of words that mean the same thing.

    • Preventative vs. preventive. Preventive is the original adjective corresponding to prevent, but preventative has gained ground and is now a common variant. The two share all their definitions.

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