SAN FRANCISCO — Chili peppers and migraines have traits in common, a fact scientists are exploiting to develop drugs capable of preventing the debilitating headache’s painful symptoms before they attack.
The link between how skin reacts when rubbed with chili oil and what happens in the brain during a migraine has attracted the world’s largest biotechnology company, Amgen Inc., and other companies seeking to create medicines for the more than 36 million Americans who suffer from migraines.
Symptoms include nausea, vomiting, dizziness and sensitivity to touch, yet treatment options are limited. Some pharmaceutical companies that have tried recently to develop migraine therapies, such as Bristol-Myers Squibb Co. and Merck & Co., have abandoned their efforts while the few drugs on the market are ineffective for many people and carry the danger of serious side-effects for those at risk of heart attack or stroke.
“Migraines are an extremely common disorder, and it effects people really in the prime of their lives,” Rob Lenz, who is leading Amgen’s migraine drug development, said in an interview. Still, no drugs have been “developed specifically for the treatment of migraines,” he said. “They were developed as anti-epileptics, or blood pressure lowering agents.”
That may soon change. Amgen, based in Thousand Oaks, Calif., and other biotechnology companies such as Alder Biopharmaceuticals Inc., Arteaus Therapeutics, and Labrys Biologics Inc., are targeting a chemical released during a migraine that carries a “pain” signal from nerve to nerve. By blocking a receptor from receiving the message, these companies aim to create drugs that cut off developing migraines before symptoms start.
Similar pain-signal transmission occurs when chili oil touches the skin. In that situation, the capsaicin in the pepper causes the body to release calcitonin gene-related peptides, or CGRP, leading to an increase in blood flow to the affected area. To show the Amgen drug works, researchers injected it under the skin of patients who had chili oil on their skin. The therapy blocked the CGRP that causes increased blood flow.
“It sounds simple, but it’s important — it tells us that our drug is getting into the body in relative concentrations that are generally well tolerated and that block CGRP,” Lenz said.
The new class of drugs under development are biologics, often delivered by injection, and are more complex, targeted and longer lasting in the body than the earlier failed attempts, Lenz said.
Amgen’s AMG 334 and Alder’s ALD 403 are being tested in the second of three clinical trials typically required for U.S. regulatory approval.
“We’ll have data on this before the year is out,” Randall Schatzman, chief executive officer of closely held Alder, based in Bothell, Wash., said in an interview.
If those trials yield results, the sales potential for these drugs will be significant. Michael Yee, an analyst with RBC Capital Markets in San Francisco, said Amgen’s new migraine treatment may reach $1 billion in sales should it gain approval.
Allergan Inc.’s Botox, used primarily for cosmetic treatments, is also approved as a preventative therapy for migraines, though only for severe sufferers who have attacks lasting four hours or more at least 15 days a month. That means only about 10 percent of migraine patients qualify for that option. Sales for Botox as a migraine treatment alone could reach $1 billion during the next decade, Anne-Elise Tobin, an analyst with Burlington, Mass.-based Decision Resources, said in an interview. The new class of drugs would be for a bigger patient population with less frequent migraines.
“Botox demonstrates the market potential for a new emerging prophylaxis therapy,” said Tobin, who estimates the global market for all migraine treatments should increase 87 percent to $5.8 billion in 2021 from $3.1 billion in 2011.
Currently, the most popular migraine treatments are oral drugs called triptans, first introduced in the 1990s, such as GlaxoSmithKline’s Imitrex, which constrict blood vessels in the brain to relieve swelling and pain.
Those medicines attempt to halt migraines once they begin. The new therapies aim to eliminate the need to wait for attacks to occur, said John Latham, chief scientific officer at Alder.
“Once the migraine symptoms flair, it’s very hard to resolve them, and most of the people at that stage of the game let it run its course,” Latham said in a phone interview. “You can go into a dark room, turn the lights off, put ear plugs on, use an ice pack, but there’s not much you can do pharmaceutically to kick the migraine back in its place.”
That’s why the new pain blocker approach holds so much promise. By blocking a receptor in the brain from receiving the message, migraines could be avoided completely, said Peter Goadsby, director of the University of California, San Francisco’s Headache Center. Goadsby helped discover CGRP’s connection to migraines and has consulted with drug companies working on developing his findings into medicines.
“What these antibody approaches hope to do is to either block the receptor or mop up the CGRP itself,” he said.
This isn’t the first time drugmakers have targeted CGRP to stop migraines. Bristol-Myers and Merck were working a few years ago on so-called small molecule therapies, taken orally, to prevent headaches. While Merck’s drug, telcagepant, worked better than a placebo in a study, the company shelved development on concerns about liver damage. Bristol-Myers also said it wouldn’t continue development of its drug.
“The whole migraine world was thrown into a tizzy because this was supposed to be the next big thing,” Cathy Glaser, president and co-founder of the Migraine Research Foundation, said in an interview. “We’re all looking for the next magic pill.”