The Cb (breezula [clascoterone]) Community Thread

petersonKj

Banned
My Regimen
You're too focused on what affects you personally. The only medical research that gets adequate funding is cancer and covid-19 research. You think hair loss research is the only avenue that's neglected because that's what you're focused on.
I know that, even within cancer research, brain cancer research is extremely underfunded despite its extremely high mortality and relatively high prevalence
 

byebyehair

Experienced Member
My Regimen
https://www.statista.com/statistics/489025/value-of-the-global-hair-loss-treatment-market/ Hairlossmarket 2010: 2B$ -> 2.8B in 2017
40% increase in 7 years. So with 10^(log(1.4)/7)-1 the anual increase over the 7 years was roughly 5%/year
https://www.usnews.com/news/blogs/data-mine/2015/05/05/global-cancer-spending-reaches-100b Cancermarket 2010 75B$ -> 100B$ in 2014
33% increase in 4 years. corresponding to 7.5%/year.

Cancer is life threatening and hairloss is a cosmetic dissorder that sucks big time...

https://www.statista.com/statistics/509679/value-of-the-global-anti-aging-market/ global anti aging market was 2018 by 50B$ and has an anual growth of 5.7%.

So i would say the demand is there... It is just like @pegasus2 pointed out a hard objectiv.

And I'm not sooo sure about Aderan and Intercytex had a sideless maintain option. Many of the guys involved went to replicel or hairclone (as far as I remember) and replicels phase 2 wasn't encouraging.
 

SomeoneHasToSayIt

Member
My Regimen
I'm in a good mood so I'm going to help you out on the off chance that your DNS has Cassiopea's website blocked. If you're betting your money on Breezula saving you then you're going to go bankrupt. Better to bet your money on a hair system. Breezula is indeed safer than finasteride, not that finasteride is dangerous. Hair loss is caused by DHT binding to androgen receptors in the hair follicle. Finasteride inhibits the systemic production of DHT. Breezula works by binding to the androgen receptors in your scalp, which prevents DHT from binding to them. Within minutes of hitting the bloodstream Breezula is metabolized into an inert substance, which means it only has effects where it is locally applied. Sounds great so far, right? The problem is that Breezula has a weak affinity for the androgen receptor. It is easily outcompeted by DHT. That's why you have to use so much of it(75mg twice a day). You have to flood your scalp with it so that it will attach to enough receptors to make a difference before DHT does. At such a high dose it is very effective over the short-term, but its effects don't last as long as minoxidil's. We need confirmation of this from their next trial, but in their last trial its effectiveness quickly declined after 6 months. This might be due to androgen receptor upregulation caused by blocking the androgen receptors continuously, thus requiring higher doses to block greater numbers of receptors. So it is certainly an effective and safe treatment in the short-term, but in the long-term it may not be very effective.

There is no release date, but it could be released in a few years. The acne version, which contains the same active ingredient, should be released next year. However, the concentration of the active drug in the acne version is only 1%, whereas you need a concentration of 7.5% to effectively combat hair loss. It should be fairly easy to get the acne version prescribed off-label for hair loss, but it will probably be very expensive since the pricing will be based on a marketed concentration of 1%, and you will have to get it compounded at 7.5%. SM04554 is the other new drug on the horizon. I think that one is more promising as a long-term treatment, but don't expect that to outperform minoxidil either.

I've read that the drug is rapidly metabolized, but how is that supported by this finding from the acne trial: "At steady-state, plasma concentrations (of CB) increased ~1.8 to 2.1 fold versus first dose with mean (coefficient of variation [CV] %) maximum plasma concentrations of 4.4 ng/mL (67%) and 4.6 ng/mL (103%) in Cohort 1 and Cohort 2, respectively. Cortexolone plasma concentrations trended below the lower limit of quantitation (0.5 ng/mL) in both cohorts."

If CB is immediately and completely metabolized to cortexolone, why is there so much more of it in the serum than the metabolite?

The study I'm quoting: https://pubmed.ncbi.nlm.nih.gov/31251549/
 

pegasus2

Senior Member
My Regimen
I've read that the drug is rapidly metabolized, but how is that supported by this finding from the acne trial: "At steady-state, plasma concentrations (of CB) increased ~1.8 to 2.1 fold versus first dose with mean (coefficient of variation [CV] %) maximum plasma concentrations of 4.4 ng/mL (67%) and 4.6 ng/mL (103%) in Cohort 1 and Cohort 2, respectively. Cortexolone plasma concentrations trended below the lower limit of quantitation (0.5 ng/mL) in both cohorts."

If CB is immediately and completely metabolized to cortexolone, why is there so much more of it in the serum than the metabolite?

The study I'm quoting: https://pubmed.ncbi.nlm.nih.gov/31251549/

How long after application did they take the readings? I'm not the expert on CB, but I think it's metabolized in minutes. If the readings were taken an hour after application then they should show higher levels of cortexolone. I'm not worried about it personally, as this drug is too weak for me. My hair loss is more severe, and requires much stronger anti-androgens than this weak sauce.
 

SomeoneHasToSayIt

Member
My Regimen
How long after application did they take the readings? I'm not the expert on CB, but I think it's metabolized in minutes. If the readings were taken an hour after application then they should show higher levels of cortexolone. I'm not worried about it personally, as this drug is too weak for me. My hair loss is more severe, and requires much stronger anti-androgens than this weak sauce.

I'll have to find the full text at some point, but it sounds like there was some degree of systemic accumulation. I wonder if the drug's weakness as an AA could explain why that doesn't cause noticeable side effects for most users.

And yeah, with a regimen like yours, it doesn't sound like CB would add much. Unfortunately, I was burned by finasteride, so my options are a bit more limited.

Edit: full study is freely available. I'll read it after work.
 

SomeoneHasToSayIt

Member
My Regimen
Ok, so I had a quick look at the study (turns out it wasn't free lol), and found that the PK tests were performed every two hours following the first and last applications of the cream. I've attached the plot of CB serum concentrations for anyone interested. Subjects were applying quite a lot of CB not just to their faces, but also shoulders, upper back, and upper chest.

There definitely is systemic accumulation of the active ingredient (looks like ~3 ng/ml average), so I can't help but wonder why this drug is considered so safe (especially for developing adolescents). To put these numbers in context, healthy testosterone levels for young men are around 6 ng/ml and healthy DHT levels around 1 ng/ml.

My knowledge of anti-androgens in general is pretty weak, and I plan to do a bit of reading on the subject in the near future, but maybe more knowledgable members can weigh in on this?
 

Attachments

  • Screen Shot 2020-06-24 at 11.05.40 AM.png
    Screen Shot 2020-06-24 at 11.05.40 AM.png
    376.3 KB · Views: 117

pegasus2

Senior Member
My Regimen
Ok, so I had a quick look at the study (turns out it wasn't free lol), and found that the PK tests were performed every two hours following the first and last applications of the cream. I've attached the plot of CB serum concentrations for anyone interested. Subjects were applying quite a lot of CB not just to their faces, but also shoulders, upper back, and upper chest.

There definitely is systemic accumulation of the active ingredient (looks like ~3 ng/ml average), so I can't help but wonder why this drug is considered so safe (especially for developing adolescents). To put these numbers in context, healthy testosterone levels for young men are around 6 ng/ml and healthy DHT levels around 1 ng/ml.

My knowledge of anti-androgens in general is pretty weak, and I plan to do a bit of reading on the subject in the near future, but maybe more knowledgable members can weigh in on this?

That's almost 100x the dose of Breezula. Probably whatever enzyme metabolizes CB is overwhelmed at that dosage. Does anyone know how it's metabolized?
 

pegasus2

Senior Member
My Regimen
That was my first thought, but I think they're describing the mass of the cream and not the active ingredient. I'll confirm in a bit.

Yeah, you're right. It says 1%. Hmm.. I don't know. That's quite a bit of accumulation for that amount.
 

Mr White

Established Member
[...] I couldn't take finasteride due to sides (peyronies), [...]

If you don't mind me asking, what does finasteride have to do with Peyronie's disease?

My penis bens a bit to the left and that always bothered me but it's not related to finasteride and I have no idea if it's PD or not.
 

Mr White

Established Member
wow I didn't realize just how bad this product is, an absolute joke.

https://www.cassiopea.com/2019/04/1...coterone-in-treating-androgenetic-alopecia-3/

they even did a shady numbers trick, with the 12 month data they published, they compared hair count with placebo hair count(because that was below baseline) thus giving the impression that hair counts actually stable in some groups. but when compared to baseline, consistent with 6 month data, it really shows what a massive failure their product really is. minoxidil actually remains above baseline for more than 5 years in one study I have read, finatsried hair count increases after 24 months still. Breezula will be an utter failure just like anything we have seen thus far. its sad, its pathetic and most and foremost, it is over

It hasn't even begun, let's at least give a try first.
 

Dimitri001

Established Member
My Regimen
Yeah, you're right. It says 1%. Hmm.. I don't know. That's quite a bit of accumulation for that amount.

Maybe it's because of the amount they applied, even if at a low concentration. If they're rubbing it all over their upper body, as SomeoneHasToSayIt mentioned, maybe the dose they take in ends up being much larger than if you applied 7% (or whatever Breezula is) to just your scalp, in which case maybe your metabolization explanation could stand.
 

-G-

Established Member
My Regimen
a pipe dream? as if it is too much to ask for to have a maintenance drug for male pattern baldness 30 years after finasteride has hit the market, as if it is too much to ask for to have a drug that does not have potential wide ranging systemic side effects and does not reduce dht in every tissue of the body? is that too much to ask for? for other diseases new drugs are coming out constantly, every f*****g year and for this crap its always just talk, big mouth talk but never anything to back it up, all the crap from 2008 and nothing worked. and why exactly is it a pipe dream? you may not understand this but they actually did have a regrowth and maintenance stem cells therapy back in 2008 but it failed due to underfunding and not meeting the goal of cloning hair. that's it. it was f*****g there. so dont tell me how maintenance without finasteride is a dream when there are literally multiple potential approaches to how one could do that and many have been explored


Do think we have been put on the back burner because our industry is based on these snake oils? That's our industry. It doesn't make sense to put more effort when we line up like horn dogs.

If this happened to girls more often maybe we would have actual change.

But hey it's men, they are used to it, they don't matter.
 

SomeoneHasToSayIt

Member
My Regimen
Maybe it's because of the amount they applied, even if at a low concentration. If they're rubbing it all over their upper body, as SomeoneHasToSayIt mentioned, maybe the dose they take in ends up being much larger than if you applied 7% (or whatever Breezula is) to just your scalp, in which case maybe your metabolization explanation could stand.

I haven't mathed it out, but I'm quite certain that the protocol used in the study leads to significantly more systemic exposure than would 1 ml of even a far higher concentration solution to the scalp (the scalp is much less permeable than the face, and the surface area of the application would be much lower ofc).

Even so, I'm confused by the study's conclusion. This is essentially the therapy that passed phase III trials. It's not some outlandish protocol; it's the approved 1% cream on a few acne-prone areas of the body. Here are some excerpts from the discussion section:

In this phase 2a, open-label study, twice daily treatment with clascoterone topical cream, 1% for 14 days demonstrated limited systemic exposure to clascoterone and favorable safety and tolerability in subjects with acne vulgaris. Clascoterone is quickly hydrolyzed by the skin and plasma esterases into the inactive parent cortexolone, the primary metabolite.

PK steady-state was achieved by day 5; systemic exposure was similar between cohorts. Cortexolone plasma concentrations trended below the lower limit of quantitation (0.5 ng/mL) in both adult and adolescent subjects indicating that clascoterone plasma concentrations were at PK steady state during the assessment of adrenal suppression potential at day 14.

The PK data demonstrate the rapid and substantial conversion of the parent molecule to a known inactive metabolite. Oral anti-androgens are associated with significant side effects demonstrating the clear benefits of topical clascoterone; it acts at the site of application only, reaching androgen receptors in the pilosebaceous units to limit androgen-mediated sebum production and inflammation,9 with minimal systemic exposure and a favorable safety profile.

It's as if I have this backwards. How do these conclusions follow from what we saw?
 

pegasus2

Senior Member
My Regimen
How is that shady? That's literally how they figure out if a drug works or not.

The shady part is that right together they used the TAHC compared to baseline for one time period, and then the TAHC compared to placebo for the other time period instead of using the same metric for both time periods. Whatever makes the drug's effect look bigger.
 

tomJ

Senior Member
My Regimen
Anyone on here try or are currently using CB? If so, where did you buy and what has been your experience this far?
Thanks!
 

NotInmywatch

Experienced Member
My Regimen
Anyone on here try or are currently using CB? If so, where did you buy and what has been your experience this far?
Thanks!
I was on CB 18 months, I bought in on wuhan pharm
I dont know if they still exist
It slows down the fall but it does not stabilize it
then I mixed it with finasteride. Still was losing hair.
horrible side effects started as usual BUT this time
I counter attacked with everything I could
iron supplements, vit D, zinc, b12 , 5g garlic, 80g broccoli
I also noticed something.
Very thin long long hairs. that is NOT androgenetic alopecia.
that is malnutrition. pure and simple.
with all that supplementation the hair recovered full thickness
there seems to be a very strong relationship between
iron pills and erection quality. Its not very well documented
but the regimen was able to reverse the finasteride side effects.
penis girth is also recovering to normal. body hair is growing too.
pubic hair was very thin. that is recovering as well.
constant shedding has stopped as well. 2, 3, 4 hairs when I wash my head.
I ditched the cb forever.
 
Top