Injectable migraine treatment being developed by Alder, Eli Lilly, Amgen and others

By Steve Brachmann
April 2, 2016

migrane-womanThere are 36 million Americans, or about 12 percent of the nation’s population, who suffer periodically from migraine headaches, according to the American Migraine Foundation. A 2013 study published by the American Headache Society found that 16.6 percent of adults aged 18 or older had experienced migraines or severe headaches over a three month period. It’s no secret that the painful health condition has a clear relationship to a person’s gender. Statistics reported by the Centers for Disease Control and Prevention (CDC) shows that females were more than twice as likely as males to experience a migraine or severe headache.

Migraines are the result of a hereditary neurological disorder which causes certain areas of the brain to become over-excited, creating the throbbing pain and increased sensitivity to lights, smells or sounds which characterize a migraine attack. Not much is known about the brain chemistry that directly causes a migraine, although it’s generally understood that hormonal fluctuations or environmental stimuli can act as triggers. Migraines themselves are not life-threatening, but they can greatly affect a person’s quality of life and ability to function normally. A 2004 Global Burden of Disease study cited by the World Health Organization (WHO) found that migraines alone accounted for about 1.3 percent of all years lost to disability.

There are two major types of treatments which are designed to help those who suffer from migraines cope with the painful effects of the condition. Prophylactic treatments which are taken before attacks to reduce their prevalence can include avoiding known triggers and taking medications such as timolol or sodium valproate. Migraines can also be treated as they’re being experienced by applying abortive treatments such as analgesics, ergot derivatives and nonsteroidal anti-inflammatory drugs (NSAIDs). Unfortunately, there is no cure that exists for migraines and many pharmaceutical treatments come with side effects.

That’s one reason why news of successful mid-stage trials for migraine treatment developed by Alder Biopharmaceuticals Inc. (NASDAQ:ALDR) has been greeted with a warm welcome from news media. The results of the trial show that an injectable treatment known as ALD403 administered four times over the course of a year reduced patient suffering from chronic migraines. These patients were suffering 15 headache days each month, eight of which were classified as migraine days. The two highest dosage levels of the drug, 300 milligrams (mg) and 100 mg, reduced migraine days by 75 percent in 41 percent of patients who were administered ALD403.

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ALD403 is a monoclonal antibody designed to target calcitonin gene-related peptide (CGRP), a small protein which is thought to be related to the increased pain sensitivity as well as the transmission of pain during migraines. CGRP and other peptides can cause the release of proinflammatory mediators, further increasing the synthesis of such peptides, and inhibiting the activity of these peptides is one method which has been tried to alleviate migraines. The pharmaceutical drug is perhaps the most advanced in Alder’s clinical pipeline and it could be approved by the U.S. Food and Drug Administration as early as 2019 if it succeeds in Phase 3 trials.

The recent Alder news shakes up a migraine drug development market which is seeing involvement from many of the major players in the biopharma industry. Eli Lilly and Company (NYSE:LLY), a multinational pharmaceutical firm headquartered in Indianapolis, IN, is working on developing a migraine treatment from a drug in its pipeline known as LY2951742, a migraine medication originally created by Eli Lilly which then repurchased its rights in January 2014 after a mid-stage trial. LY2951742 is another CGRP-targeting monoclonal antibody which is also subcutaneously injected into a patient, although it’s administered monthly instead of every few months.

Last June, Eli Lilly announced a successful Phase 2b study of the drug in patients with episodic migraine. The drug exhibited statistically significant reductions in migraine occurrence along with a good safety and tolerability profile. One-third of the patients receiving this drug twice per month achieved a 100 percent reduction in migraine headache days. The company has launched two Phase 3 trials which will look at the effect of LY2951742 in those suffering from cluster headaches.

American biopharmaceutical firm Amgen Inc. (NASDAQ:AMGN) of Thousand Oaks, CA, is another player in this large pool of drug developers targeting CGRP pathways for treating migraines. A Phase 2 study which also completed last June found that the company’s experimental drug AMG334 was able to cut migraine days by 3.4 per month in patients who were receiving the highest dosage, using a patient baseline of 8.7 migraine days per month. In its trial, AMG334 was subcutaneously injected into patients on a monthly basis at three different dosage levels: 7 mg, 21 mg and 70 mg. The greatest response was seen in those patients who were being administered the 70 mg dose. Amgen is currently recruiting participants for Phase III trials of AMG334.

The value of the migraine drug market has not gone unnoticed by the world’s largest developer of generic drugs, Teva Pharmaceuticals (NYSE:TEVA) of Petah Tikva, Israel. The company, which had increased its migraine treatment pipeline in June 2014 when it purchased San Mateo’s Labrys Biologics, a company also researching neuropeptides and their relation to migraines, for a total of $825 million. Teva’s main pharmaceutical in this sector is TEV-48125, yet another monoclonal antibody targeting CGRP which is administered by injection. Last February, Teva announced successful Phase 2b trials of TEV-48125, which found significant reductions in cumulative headache hours and the number of headache days per month when the drug was administered at two different dosage levels. Participating patients received the drug once each month for three months and although patients receiving the drug experienced higher rates of redness and injection site discomfort than those receiving a placebo, no serious adverse side effects developed. Data from the study caused Teva’s stock to pop 1.5 percent after released the chronic migraine drug trial data.

Even with all of this focus on regulating CGRP-related pathways within the human brain and the potential it has for alleviating headaches, we’re still a ways off from understanding how to stop migraines in their tracks. Recent studies released by academic institutions show how the issue could be tied into a wide scope of emotional and physiological functions of the human body. Researchers from the University of Mississippi recently concluded that brief sleep therapy sessions with a professional therapist to address issues of insomnia, which affect a high rate of migraine sufferers, had a greater ability to reduce migraines when compared to patients receiving control treatments for issues other than insomnia from professional therapists. Childhood emotional abuse could also have a strong link to those who suffer migraines as adults, according to a study coming out of the University of Toledo. The study involved 14,484 people aged 24 to 32, 14 percent of whom suffered from migraines. Among the migraine sufferers, almost half had remarked that they had been emotionally abused as a child. Correlation rates among physical and sexual abuse causing migraines, however, were much lower.

As with migraine treatment, and just about everything else in this world, there’s an app for that. One such migraine treatment app is Migraine Buddy, an app which reportedly claims to be able to predict up to 90 percent of migraines before they happen. The app asks users to record migraine frequency and intensity, symptoms, medications and other factors which it analyzes to try and determine a person’s triggers. It also provides an automatic sleep tracker, further suggesting a link between proper sleeping habits and migraine frequency. The app markets its cloud data storage as being compliant with HIPAA to keep private medical data secure.

The Author

Steve Brachmann

Steve Brachmann is a freelance journalist located in Buffalo, New York. He has worked professionally as a freelancer for more than a decade. He writes about technology and innovation. His work has been published by The Buffalo News, The Hamburg Sun, USAToday.com, Chron.com, Motley Fool and OpenLettersMonthly.com. Steve also provides website copy and documents for various business clients and is available for research projects and freelance work.

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