People with migraine may have a new option for treatment soon, and these new medications aren’t just about treating the pain after it’s begun – they prevent migraines from getting started. While there are other medications used to prevent migraines, the currently available medications were all originally developed for other uses, and some have significant side effects.
The new potential treatment option targets CGRP – calcitonin-gene-related peptide. CGRP is a small protein that acts as a neurotransmitter (chemical messenger) in the brain. Researchers noticed that CGRP levels are high during a migraine and subside after the migraine is over, so they created monoclonal antibodies that target and block either CGRP or the receptors it binds to. All of the CGRP treatments are given by injection: some are injected subcutaneously (under the skin) and others are injected intravenously (into a vein).1,2
Four pharmaceutical products are in a race to see which will get to market first. While the process to get a drug through clinical trials and approved by the U.S. Food and Drug Administration (FDA) is long and arduous, all four are nearing the end with, to date, promising results. Before a pharmaceutical company can submit their data to the FDA for consideration, they must complete Phase III clinical trials, which study a treatment in large numbers of patients to determine its effectiveness and safety.
Teva announced positive results for chronic migraine
Pharmaceutical company Teva recently reported positive results from the Phase III trials for its CGRP treatment, which is currently known as fremanezumab. (Drugs get a brand name if they get approval from the FDA.) The study evaluated 1,130 patients with chronic migraine and randomly assigned them to one of three groups, and each group received treatment for a three-month (12-week) period. The first group received an injection of 675 mg fremanezumab at the beginning of the treatment period, followed by monthly 225 mg fremanezumab for the next two months. The second treatment group received an injection of 675 mg fremanezumab at the beginning of the treatment period, followed by placebo injections for the next two months, and the third treatment group received three monthly injections of placebo.
The patients who received fremanezumab experienced statistically significantly fewer migraine days per month compared to placebo: those who received fremanezumab monthly had 4.6 fewer migraine days, those who received fremanezumab quarterly had 4.3 fewer migraine days, and those who received placebo had 2.5 fewer migraine days. The most commonly reported side effect in the study was pain at the injection site.
Teva is still awaiting results from their Phase III trial of fremanezumab in people with episodic migraine, and they hope to submit their data from both trials to the FDA later this year.3
Lilly announced positive results for chronic and episodic migraine
Eli Lilly has also released results from three Phase III trials of its CGRP treatment, galcanezumab. Two of the trials studied people with episodic migraines for a six-month treatment period, where patients were randomly assigned to receive once monthly injections of 120 mg galcanezumab, 240 mg galcanezumab, or placebo. The first trial showed that those receiving the 120 mg dose had 4.7 fewer migraine days, and those receiving the 240 mg dose had 4.6 fewer migraine days, compared to 2.8 fewer migraine days for those receiving placebo. The second trial also showed a benefit: those receiving the 120 mg dose had 4.3 fewer migraine days, and those with the 240 mg dose had 4.2 fewer migraine days, compared to 2.3 fewer migraine days for those receiving placebo. Lilly’s third study evaluated galcanezumab in chronic migraine over a three-month period, and patients receiving 120 mg had 4.8 fewer days, and those receiving the 240 mg had 4.6 fewer days, compared to 2.7 fewer days for placebo. The most common side effects were reactions at the injection site, including pain.
Lilly plans to submit the data from these trials to the FDA for approval later this year.4
Alder has promising data from early trials
Alder BioPharmaceuticals has released results from its Phase II trials of their CGRP treatment, eptinezumab, but their Phase III trials are still ongoing. The early trials showed a significant benefit compared to placebo, and they hope to have Phase III trial data to submit to the FDA next year.5
Amgen has submitted its positive results to the FDA for approval
Amgen has submitted its data to the FDA for approval of its CGRP treatment, erenumab. While they are the first to submit, it doesn’t necessarily mean their product will be the first to be approved. Amgen recently presented data from their Phase III clinical trials at the 59th Annual Scientific Meeting of the American Headache Society. Like the other CGRP products under investigation, erenumab showed statistically significant benefit compared to placebo in episodic migraine. Compared to a 3.5 day reduction with placebo, patients receiving erenumab had 6.6 fewer days of migraine per month.6,7
Promising, yet still unknowns
The option of a new treatment for migraines is promising, and the data from these trials show that all the CGRP treatments do have benefits. And while the side effects seem minimal, long-term safety data is still unknown. The price and insurance coverage of these products is also yet-to-be-determined.
CGRP drugs do seem to reduce the number of migraine days, but they don’t completely eliminate migraines or the need for other treatments, such as analgesics. Still, the promise of a new potential treatment, and one that is targeted specifically for migraines, provides hope to those who suffer with the debilitating pain, sensitivity to light and sound, vision changes, and other impactful symptoms from migraines.
Pharmaceutical Journal. Accessed online on 7/6/17 at http://www.pharmaceutical-journal.com/news-and-analysis/features/targeting-the-cgrp-protein-could-lead-to-a-preventative-treatment-for-migraine/20201917.article.
Goadsby PJ, Edvinsson L & Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990;28:183–187. doi: 10.1002/ana.410280213
Teva. Accessed online on 7/6/17 at http://www.tevapharm.com/news/teva_announces_positive_results_for_phase_iii_study_of_fremanezumab_for_the_prevention_of_chronic_migraine_05_17.aspx
Eli Lilly. Accessed online on 7/6/17 at https://investor.lilly.com/releasedetail.cfm?ReleaseID=1026201
Alder BioPharmaceuticals. Accessed online on 7/6/17 at http://investor.alderbio.com/releasedetail.cfm?releaseid=1023586
Amgen. Accessed online on 7/6/17 at http://wwwext.amgen.com/media/news-releases/2017/05/amgen-submits-biologics-license-application-to-the-fda-for-erenumab/
PR Newswire. Accessed online on 7/6/17 at http://www.prnewswire.com/news-releases/amgen-presents-erenumab-data-at-the-59th-annual-scientific-meeting-of-the-american-headache-society-300471243.html