March 6, 2012
Pain-Wracked Migraine Patients’ Unmet Needs Targeted by Map’s Inhaled Drug
By Ryan Flinn
When Sara Gibson’s head starts to tingle, she knows she’s in trouble.
The sensation means the 39-year-old mother of two is about to get a migraine, a searing pain that radiates from the base of her skull forward, leaving her incapacitated for days. When it happens, her husband often leaves work to care for her children while she hides in a dark bedroom to avoid the noise, light or movement that can exacerbate her condition.
“The pain is so bad, I can’t function.” Gibson said.
Not much helps. Therapies available at home are too weak or cause rebound headaches later, Gibson said. Others, such as the 65-year-old treatment known as DHE and morphine-like narcotics, must be given by a doctor. That means visiting a bright and noisy emergency room that can ramp up her pain.
Companies led by Map Pharmaceuticals Inc. (MAPP) are pushing to develop better treatments for the 36 million Americans who get migraines. Regulators are set to announce this month if Map’s Levadex, an inhaled form of DHE that can be taken at home, can be marketed. If so, it may be worth $1 billion a year by 2020.
“The migraine market represents a massive unmet need,” said Randall Stanicky, an analyst at Canaccord Genuity Corp. in New York, in a telephone interview. “It’s a very big market and while there are several therapies out there, there’s not that many that have proven effective.”
Gibson, of San Leandro, California, suffers as many as five migraines a month and each can last for three or four days, she said in a telephone interview.
If her husband can’t make it home when a migraine hits, “I spend the day being a bad mom,” she said, describing symptoms that include pain, nausea, vomiting, dizziness and sensitivity to touch, all typical for the migraine sufferer, according to the Migraine Research Foundation. About 9 percent of patients have migraines 15 or more days a month, the New York-based group reports on its website.
For those whose symptoms are severe, treatment options are limited, according to Stephen Silberstein, a neurologist and director of the Jefferson Headache Center in Philadelphia.
While powerful narcotics, such as Sanofi-Aventis SA’s Demerol or Abbott Laboratories’ Dilaudid, can reduce the pain, they carry side effects that can be difficult, particularly for someone with a normal schedule at work or home, Gibson said.
“You’re not super functional,” she said. “The pain is still there, you’re just under a cloud of narcotics.”
Oral drugs called triptans, such as GlaxoSmithKline Plc (GSK)’s Imitrex, can be used at home. They don’t work for everyone, though, shouldn’t be taken by those at risk of stroke or heart attack, and they carry their own set of side effects.
DHE, or dihydroergotamine, works by narrowing blood vessels in the brain that swell during a migraine. The present form of the drug, approved by the Food and Drug Administration in 1946, has been shown to be effective against severe pain. It must be administered intravenously or through injection, though, forcing patients to go to emergency rooms or doctor’s offices at the worst possible time.
With Map’s drug, “you can breathe it in at home, and in 10 to 12 minutes, have your migraine treated,” Chief Executive Officer Tim Nelson said in an interview at his company’s Mountain View, California offices.
For Map, that difference can be lucrative. While the company hasn’t set a price for Levadex, it will probably be similar to current therapies that cost from $20 to $80 a dose, Nelson said. That’s a figure that would put the drug’s sales in the range of $500 million to $1 billion a year by 2020, said Anne-Elise Tobin, an analyst with Burlington, Massachusetts- based Decision Resources.
Rising Global Market
The global market for migraine treatments should increase 38 percent to $4.4 billion from $3.2 billion in 2013, Tobin said in a telephone interview.
Map declined less than 1 percent to $16.66 at 4 p.m. New York time. The shares are up 2.3 percent in the last 12 months.
Map signed a profit-sharing agreement with Botox maker Allergan Inc. (AGN) to help sell Levadex. While Botox, a purified form of the poison botulinum, is best known as a cosmetic therapy for smoothing wrinkles, it was approved in October for patients with chronic migraines. These patients suffer attacks at least 15 days a month, with pain lasting at least four hours.
Map is seeking U.S. approval for Levadex’s sale to acute patients, or those with fewer attacks over a month’s time, according to a company statement.
“We can have the advantage of promoting two products in the same calls with the same sales persons,” said Allergan Chief Executive Officer David Pyott in a telephone interview. “We’re very happy and have a great collaboration behind the scenes.”
Levadex won’t be the first noninjectable form of DHE. Novartis AG, based in Basel, Switzerland, won regulatory approval for a nasal-spray version in 1998, though it didn’t work as well as the injection because most of the medicine ended up being swallowed, said Peter Goadsby, director of the University of California, San Francisco’s Headache Center.
“I exposed some patients to it, got a little bit of experience with it, and concluded it had very little to offer,” he said in a telephone interview.
Levadex may have a much better absorption rate, said Goadsby, who has been a paid consultant for Map in the past.
While Levadex is the next migraine product in line for U.S. approval, at least a dozen active late-stage trials of new therapies are ongoing, testing products including an Ibuprofen- caffeine combination, acupressure and a nerve stimulation device, according to data compiled by Bloomberg.
CoLucid Pharmaceuticals Inc., a closely held drugmaker in Durham, North Carolina, is testing a new class of drug that targets a receptor that some triptans affect, but in a cranial nerve, instead of blood vessels. The drug, lasmiditan, has completed some Phase 2 studies. Three stages of clinical trials generally are required for U.S. regulatory approval.
Other companies are following the Map model, developing new ways to deliver established migraine medicines.
IntelGenx Technologies Corp. (IGXT), of Ville Sainte-Laurent, Canada, and Tel Aviv-based RedHill Biopharma Ltd. (RDHL) are reformulating triptans into a digestible film strip, and are in second-stage trials.
NuPathe Inc. (PATH), based in Conshohocken, Pennsylvania, is seeking approval for the first triptan-based skin patch, called Zelrix. While the U.S. regulators rejected the company’s bid in August, citing “chemistry, manufacturing and safety” questions, NuPathe has said it plans to resubmit this year.
“In some ways, it’s easier to reformulate a treatment that’s already known,” said Decision Resources’ Tobin. “It’s an easier path to development than trying to come up with a new molecular entity.”
Gibson has experimented with a range of therapies since she had her first migraine in her early 20s, she said. Her attacks have grown in frequency as she got older and trying to get help from the medical establishment hasn’t always been easy.
Doctors would sometimes question whether she was really in pain and whether her frequent return trips for pain medication meant she was an addict.
“It was horrible -- they would keep me there for a long time, because they were trying to figure out, ‘Are you drug seeking?’” she said. “Some people react to it like it’s the 1900s and they just think you’re suffering from hysteria.”
While triptans, which can be taken at home, eliminated the pain, they cause rebound headaches for her later, she said, and they carry side effects that make it tough to deal with kids. These can include increased nausea, flushing and muscle weakness. Gibson has also tried to avoid them while nursing her 5-month-old daughter, she said.
Now, Gibson frequently finds herself in a situation where she’s weighing whether to take those drugs, despite the side effects, or seek help at the emergency room.
“Anything that doesn’t create the rebound effect, I’d be all about it,” she said. “I can’t go to an ER every time I have a headache, that’s just not going to work.”
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