A breakthrough year indeed! With CGRP antibodies leading the charge.
It has been over a year since we reported on the great promise of CGRP antibodies and the immense promise they hold for a true, scientifically validated, migraine prevention medication. Our Twitter postings, for those that follow us, have kept pace with the developments, but it seems an opportune time to pull the story together. As you recall, calcitonin gene- related peptides (CGRP), a group of small proteins, have been implicated in the initiation of migraine attacks. Studies are showing we can effectively interrupt this process in one of two ways. The first is by injecting marvelous little monoclonal antibodies that target CGRP and prevent the attack. The second is by using a small molecule orally that aborts the attack. Both approaches are currently in clinical trials.
Five main companies are actively studying the drugs that impact CGRP and migraines(there are others). Namely Teva Pharmaceuticals, Eli Lilly, Alder Pharmaceuticals , Amgen, and Merck. These are big players in the Pharma world and no expense is being spared to break open a market that easily tops 50 million sufferers worldwide.
All of these medications have completed Phase 2 trials with some pretty amazing results.
According to Dr. Peter Goadsby:
“What we typically look at are 50% responder rate. About half of the patients will have 50% of their attacks go away. About 30% of people will have 75% of their attacks will go away. And a little under 20% will have all their attacks go away. If you’re sitting here (reading) this and you’ve got 20 days of migraine a month, then the idea that 15 [attack days] would go away, that’s a pretty good deal. And even if 10 [days] would go away, that’s a substantial improvement in terms of disability. It’s not only the migraine day, of course, it’s the day before when you don’t quite feel right, and the day after when you’re recovering from it. Migraine not just about the attacks, particularly for chronic migraine patients, it’s about living in a fog of abnormality which never really allows them to do all the things they want to do and reach full potential that they’re entitled to.”
Now these medications move into Phase 3 trials, which, if successful, means they may come to market in about three years. Phase 3 needs to establish a few things to round things off for the regulators. One needs to study a much larger sample of subjects to make sure the medication really works. Also, looking at a larger sample insures there are no overriding safety concerns. Anecdotally, most experts agree that these medications have a very low side effect profile. Phase 3 will hopefully confirm that critical point.
Not surprisingly, when large studies of this nature are undertaken, other, unexpected outcomes are revealed. We’ll share several here. Keep in mind they will need to be validated by the more expansive Phase 3 trials, if not more.
In one study, the monoclonal antibody that targets the CGRP receptor has enhanced subject-reported “wellness” on headache-free days. Subjects report a reduction of fatigue along with enhanced focus, concentration, and improved interaction in daily life , as reported in an abstract presented at the annual meeting of the American Headache Society. So not only migraine prevention/reduction, but better days generally in between doses.
Also on the watch list, Lilly awaits results of a galcanezumab study focusing on chronic cluster headaches before the end of 2016. This should be followed by numbers on episodic headaches by year end 2017. The cluster project is also being tested in the highly charged migraine arena, but could become the first anti-CGRP antibody marketed for cluster headaches. As you know cluster headaches, also known as “suicide headaches” have been stubbornly resistant to medical intervention.
Finally, the study of the action of CGRP monoclonal antibodies and new (2016) genetic findings are still in their infancy, but hold much promise. We still do not understand how the genetic findings are linked to responses to CGRP-blocking antibodies The recent genome wide association (GWA) study results have supplemented the debate concerning site of action of these drugs because the new CGRP antibodies have a molecular size too large to get across the blood brain barrier. The genetic findings therefore call for new study designs, suggesting a focus on vascular control, that may suggest individualized treatment outcomes and new treatment choices. The goal is, naturally more personalized care. However, elegant studies with larger sample sizes and a comprehensive understanding of how infrequent and rare variants influence the disease characteristics, will be required.
So there is your update, and a promising one it is for both migraineurs and cluster sufferers alike. Also, if you are inclined to check out ongoing clinical trials in your area please go to ClinicalTrials.gov and search for “Migraine CGRP” You would be helping the research on CGRP in general, along with possible personal migraine benefits.
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