Previous post on CGRP.
I am personally quite excited about this research. The studies have been large and plentiful and the results significant. I am also a preventative non-responder, so something different, for migraines specifically, gives me hope. And you can’t beat a little hope, can you? I have heard a projected timeline for the release of some of these targeted CGRP medications for the later end of 2018 which is not too far when you thing about it.
CGRP targeted treatment is the first migraine preventative for migraines ever. Ever. The research suggests targeting calcitonin gene-related peptide (CGRP), a protein that helps with triggering, sending, and heightening sensitivity to the migraine pain, can help improve migraine intensity and frequency in migraineurs when blocked. CGRP is released during a migraine. It is a strong vasodilator of cerebral arteries. The serum CGRP levels are elevated in migraine and persistently in chronic migraines. CGRP basically binds to receptors that activate and cause symptoms of migraines like vasodilation, inflammation and pain. If you were to be given an infusion of it, it would trigger a migraine attack. Therefore, the idea is for anti-CGRP and anti-CGRP receptor monoclonal antibodies to help prevent the migraine attacks from happening. It is ‘”the best validated target for migraine, ever,’ says David Dodick, a neurologist at the Mayo Clinic in Phoenix. It may also help finally solve the centuries-old puzzle of what triggers the complex events of a migraine attack, which can cause brain activity to be ‘completely disregulated’ for several days, similar to epilepsy and other recurrent, seizurelike disorders, says Michel Ferrari, a neurologist at Leiden University in the Netherlands.’ (Science mag) They are well tolerated medications without the 801 side effects we tend to see in preventatives now.
- Triptans work partly by increasing the amount of calcium inside cells, which then appears to decrease CGRP. (Migraine.com)
- OnabotulinumtoxinA (BOTOX) is suggested to work by preventing the release of CGRP. (Migraine.com)
“After finding CGRP is plentiful in brain pathways that process pain and in brain regions that regulate blood flow, neurologist Lars Edvinsson, of Lund University in Sweden, wondered whether CGRP is involved in migraines. His group soon found that CGRP can trigger what was then considered a hallmark sign of migraines: When released from the trigeminovascular nerves, it is a powerful vasodilator of cerebral blood vessels. In 1990, he paired up with neurologist Peter Goadsby, now at King’s College London, to further explore CGRP’s role in migraine patients. After getting permission to take blood samples from the jugular veins of people who had come to the emergency room for a severe migraine, the researchers measured the amounts of a range of different peptides, including Substance P, during and after attacks. ‘The amazing thing was that CGRP was the only peptide that was significantly released,’ Edvinsson says.” (Science mag)
Here is some of the research on CGRP going on right now. There is a lot and many of them are in Phase III, so this is but a taste.
Study 1: Phase III
577 patients with episodic migraine were randomized to placebo to erenumab 70 mg. Patients reported a mean 8.3 monthly migraine days at baseline. Those receiving the medication experienced a mean -2.9 days reduction from baseline compared to -1.8 of placebo. Conclusions “Erenumab statistically significantly reduced migraine frequency, acute migraine-specific medication use and a greater proportion of patients achieved ≥50% reduction in MMDs, compared with placebo, in this phase 3 trial in EM.”
Study 2: Phase III
955 episodic migrainuers were involved in this double-blind placebo controlled trial. It involved erenumab 70 mg or 140 mg for 24 weeks. There was an 8.3 monthly migraine at baseline. At 70 mg there was a -3.2 reduction, at 140 mg a -3.7 reductions and placebo was -1.8 reductions. The tolerability was similar to the placebo and subjects reported nasopharyngitis, upper-respiratory-tract infection, and sinusitis. Conclusions “Erenumab 70 mg and 140 mg significantly reduced migraine frequency and use of migraine-specific medications, reducing migraine’s impact on physical impairment and EA compared with placebo in this EM trial. Numerically greater efficacy was observed for the 140 mg dose consistently across all endpoints.”
Study 3: Chronic migraines Phase II
Included her subjects with 15-28 headache days, of which at least 8 were migraine days set to receive intravenous dose of ALD403 300mg, 100mg, 30mg or placebo. 616 received treatment. Baseline migraine days were between 16.2-16.5. Subjects with a 75% reduction in migraine days for the 12 week trial was 33%, 31%, 28%, 27% and 21% for ALD403 300mg, 100mg, 30mg, 10mg and placebo. The percentage of severe migraine decreased relative to baseline -21%, -16%, -18%, -16% and -10% for ALD403 300mg, 100mg, 30mg, 10mg and placebo. It was well tolerated with no serious drug-related adverse effects. Conclusions: “ALD403 100mg and 300mg significantly reduced migraine days in patients with chronic migraine as measured by 75% responder rates. All doses of ALD403 significantly reduced the percentage of migraine attacks that the patients reported as severe.”
Study 4: 3 studies involving Galcanezumab
ELVOLVE-1 & EVOLVE-2 were on episodic migraine over a 6 month period with either 120mg or 240mg. Patients had an average 9.1 baseline. In EVOLVE-1 the average reduction in monthly migraine days was 4.7 for 120mg and 4.6 for 240mg compared to 2.8 for placebo. In EVOLVE-2 average reduction was 4.3 days for 120 mg and 4.2 days for 240 mg rather than 2.3 for placebo.
REGAIN, on the other hand, was for chronic migraines, over a 3 month period for 120 mg and 240mg. the subjects had an average of 19.4 at baseline. There was a significant reduction at 4.8 at the 120mg and 4.6 days for the 240mgs compared to the 2.7 for placebo.
Over half of patients are seeing a 50% reduction in migraine frequency while using the CGRP drugs — some even more. Dr. Peter Goadsby, director of the UCSF Headache Center in San Francisco, called it ‘a truly landmark development’ that will offer many patients ‘freedom from the daily grind of being a migraine sufferer.’ MigraineAgain