FDA approval...new migraine preventive drug...

[jon019]

Yeah...I know...the "M" word...but clusterheads have had to tag along behind treatments for that FOREVER anyway....

Best

Jon

PS I tried to post in a more friendly form with active links...unable...try FDA.gov (Ajovy)

                       
     The Division of Drug Information (DDI) - serving the public by providing information on human drug products and drug product regulation by FDA
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     Today, the US Food and Drug Administration (FDA) approved Ajovy (fremanezumab-vfrm) for the preventive treatment of migraine in adults. Ajovy is the second FDA-approved preventive migraine treatment in a new class of drugs that work by blocking the activity of calcitonin gene-related peptide (CGRP), a molecule that is involved in migraine attacks. Aimovig (erenumab-aooe), the first in this class, was approved on May 17, 2018.

Patients often describe migraine headache pain as an intense pulsing or throbbing pain in one area of the head. Additional symptoms include nausea and/or vomiting and sensitivity to light and sound. Migraine attacks can cause significant pain or hours to days and can be so severe that the pain is disabling. Warning symptoms known as aura may occur before or with the headache. These can include flashes of light, blind spots, or tingling on one side of your face or in your arm or leg.

Ajovy is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients. Hypersensitivity reactions, including rash, pruritis (itching), drug hypersensitivity, and urticaria (hives) were reported with Ajovy in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. The most common adverse reactions were injection site reactions and infections.

For more information, please visit: Ajovy (fremanezumab-vfrm) .

                 
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Edited September 14, 2018 by jon019
spelling

[CHfather]

Thanks, jon'.  I posted some info a while back on the Research board that suggested that this type of drug ought to work well for people with CH, too.  No long-term studies yet of any kind of use, so l-t side effects undetermined.

[CH1234]

Edit

[CHfather]

59 minutes ago, AJOVY said:

One thing I want to mention about Ajovy and is that is IS approved for patients with cluster migraines, both chronic and episodic.

I know you're trying to be helpful (and promote a product, which is generally against the rules of the board but I suppose could be waived in this case(?)), but Ajovy is not, to the best of my knowledge and with reference to the Ajovy website, approved for cluster headache -- and there's really no such thing as "cluster migraine." 

So unless you can clarify, this might be creating false expectations among people with cluster headache, which is not a form of migraine. I'd be happy to be shown that I'm wrong, since I think this treatment is important.

[ThatHurtsMyHead]

I just did a quick read up on ajovy.  Not impressed.  For migraine studies, the placebo had a 75% reduction of headache days as compared to this drug.  Basically for migraine it was only 25% better than a placebo.  Zero information for CH.  Given it has such a poor impact on migraine, I wouldn't expect it to have any positive effect on CH.  Just my opinion.  

J

[CHfather]

Thanks, THMH.  Here's more unsatisfying news: "A pre-specified futility analysis of the chronic cluster headache study revealed that the primary endpoint of mean change from baseline in the monthly average number of cluster headache attacks during the 12-week treatment period is unlikely to be met."

https://www.tevapharm.com/news/teva_provides_update_on_clinical_trial_of_fremanezumab_for_use_in_chronic_cluster_headache_06_18.aspx

[ThatHurtsMyHead]

It's always good to bring new information though   Otherwise we'd all be sticking ourselves with imitrex till our hearts exploded by now.

J

[xxx]

Here's some good news on preventing migraines...

Curr Med Res Opin. 2018 Sep 5:1-22. doi: 10.1080/03007995.2018.1519503. [Epub ahead of print]

A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D3 supplementation in adult patients with migraine.
Gazerani P1, Fuglsang R1, Pedersen JG1, Sørensen J1, Kjeldsen JL1, Yassin H1, Nedergaard BS2.

Abstract
BACKGROUND:
Vitamin D levels have been linked to certain pain states, including migraine. We investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460).

METHODS:
A randomized, double-blind, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18-65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin® (n = 24, 18 women and 6 men, 100 μg/day D3-Vitamin®) or placebo (n = 24, 18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e., experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25(OH)D and 1,25(OH)2D were assessed from baseline to week 24.

RESULTS:
The number of headache days changed from 6.14±3.60 in the treatment group and 5.72±4.52 in the placebo group at baseline to 3.28±3.24 and 4.93±3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin® demonstrated a significant decrease (p < 0.001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin® group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)2D. No side effects were reported or noted.

CONCLUSIONS:
D3-Vitamin® was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D3 might be one of the prophylactic options for adult patients with migraine.

My Comments:

Putting the results of this RCT in perspective, migraineurs taking 4,000 IU/day vitamin D3 experienced an average reduction of 2.86 migraine days/month while migraineurs taking the placebo experienced a reduction of 0.79 migraine days/month.  Doing the math, migraineurs taking 4000 IU/day vitamin D3 experienced 2.07 fewer monthly migraine days/month than migraineurs taking the placebo.

Doing a similar analysis of Aimovig (Erenumab), one of the two approved monoclonal antibody (mAb) migraine preventatives, using the same placebo-controlled study design with the same 3-month end point found it achieved a reduction in migraine days/month between 1.4 and 1.9 migraine days/month better than the placebo depending on the dose.

Three months worth of vitamin D3 at 4,000 IU/day (5 cents/day) costs roughly $4.50 while three months of Aimovig at ~$600/month costs $1,800...  You can do your own math on relative cost benefits...

BTW... It was posts like this I made on Facebook that likely caused Facebook management to block my access...

Take care,

V/R, Batch

 

 

[jon019]

Batch...there's this curve....and you are so far ahead of it that they can't even see your dust...….

….thanks for posting this...a piece of science we can wave in front of the droids we encounter in the medical community...who sadly sometimes don't even believe it then....see O2 deniers for CH...………………

Best

Jon

[xxx]

Jon,

Thank you for the kind words.  I've been in touch with the Principal Investigator for the vitamin D3 migraine prophylaxis RCT.  He and his team are working the final manuscript for publication.  Once that's out of the way and they can find the funding, a follow-on RCT using a vitamin D3 physiological dose of 10,000 IU/day is on their list of things to do.

There's a good reason why the mAb RCTs can't achieve better efficacy.  When you consider the site of action are neurons within the brain that produce calcitonin gene-related peptide (CGRP) and mechanism of action they espouse is neutralization of CGRP, the first step in these two processes is getting the mAb into the brain.  That's a very real problem Big Pharma has yet to solve.   The maximum opening size through the tightly packed endothelial cells forming the blood brain barrier (BBB) is a molecular mass of 400 Da (Daltons).  The mAbs have a molecular mass of 150 kDa (150,000 Da)... 375 times larger than openings through the BBB.  If the mAbs cannot pass through the BBB to enter neurons throughout the brain, neutralizing CGRP within these neurons is a non-starter.  My guess is the reduction in migraine days made possible with mAbs is due to reducing serum CGRP.

For reference, vitamin D3 has a molecular mass of 385 Da so passes readily through the BBB and into neurons where it's hydroxylated by enzymes to 1,25(OH)2D3, the genetically active vitamin D3 metabolite.  It in turn attaches to Vitamin D Receptors (VDR) at the genetic layer initiating the genetic expression that down-regulates CGRP expression... and in the process, prevents our CH and MH.  Better living through chemistry...  and molecular biology...  That's my SWAG... and I'll stick with it until a better mechanism of action is found.

Take care,

V/R, Batch

[tuesnxt]

As I've yet to be able to convince my doctor that my headaches are cluster headaches and not migraines (he continues to insist they are the SAME THING), I left his office the proud owner of a tiny band-aid where I was pricked with a needle from a dose of Ajovy. I'll be the resident test case.

[ThatHurtsMyHead]

tuesnxt,

It baffles me almost daily how some doctors are allowed to practice medicine.  Him saying CH and a Migraine are the same is like saying heartburn and a heart attack are the same..   geesh....  Sorry you have to deal with such incompetence.

J

[tuesnxt]

Well, after less than 10 days from the initial injection of Anjovy, the cluster headaches are back. October is my worst month anyway. So, I am treating them as I always have with standard abortive techniques but so far, Anjovy (or anchovies, as I call it) is no miracle cure.

[ThatHurtsMyHead]

tuesnxt,

Thanks for the info!  The best we can do is share what works and doesn't, to help the next person.  I'm guessing you already have O2?

Cheers,

J

[jon019]

6 hours ago, ThatHurtsMyHead said:

 

Thanks for the info!  The best we can do is share what works and doesn't, to help the next person.  I'm guessing you already have O2?

SO TRUE....sometimes all we got is clusterville and our supporters....PLUS an o2 mention!!!

...I like my anchovies on pizza.....it's the umami!

[CHMom]

Out of complete desperation, I tried Ajovy for my cluster headaches this past January (2020), upon the recommendation of my neurologist. For me, it was a godsend. It immediately ended my cluster cycle.