I finally got around to trying CB-03-01.
I had heard varying opinions on its therapeutic promise in the community, but at the end of the day I had to do a CB-03-01 review myself to see if this compound is superior to other alternatives we already have at our disposal.
Breezula (developmental code name CB-03-01) is a synthetic steroidal antiandrogen being developed as a potential treatment for androgenic alopecia (male-pattern baldness).
CB-03-01 is probably going to be the first topical antiandrogen that actually gets approved for human use as a hair loss prevention treatment.
The first thing that should be stressed when it comes to something like this is that regrowth will not be common with its use.
Prevention is the goal with something like this.
The clinical data on CB-03-01 isn't overly impressive in terms of hair loss prevention and reversal.
The main issue with treatment options like this are expectations.
You should lower your expectations when it comes to topical antiandrogens.
Preventing further loss is the goal, and any regrowth is a fringe benefit.
Having something with a high level of tolerability, low side effect profile, and can also effectively compete at the androgen receptor locally with ALL endogenous androgens, can be a critical component of a comprehensive hair loss prevention protocol.
RU58841 Vs. CB-03-01 Results – In My Experience
Having years of experience under my belt with RU58841 and other topical compounds, I felt like I had a good reference point to judge the overall efficacy of CB-03-01.
For me personally, CB-03-01 didn't cause any side effects, and neither has RU58841.
How effective was it as a topical antiandrogen?
Mild in my opinion, but still promising.
RU58841 seems stronger to me, however, that doesn't mean that something with a lower potency milligram for milligram can't just be dosed higher to yield a similar outcome.
The issue with that is that CB-03-01 is extremely cost prohibitive right now.
A minority of individuals have found CB-03-01 to be more tolerable than RU58841 with a formidable antiandrogen effect.
However, the majority of individuals, myself included, have not found it to be on par with RU58841, and it is far more expensive.
CB-03-01 Vs. Other Topical AntiAndrogens
If a very high dose of CB-03-01 was the same price as a moderate dose of RU58841, then I believe that would then potentially justify it as the superior alternative, but as of now it seems that there are more cost effective alternatives to CB-03-01 that are also just as effective, if not more effective.
And that's just comparing CB-03-01 to what is viewed in our community as the most traditional antiandrogen.
I believe there are other topical androgen receptor agonists and antagonists that could also have more therapeutic promise than both.
For example, the molecular weight of certain Selective Androgen Receptor Modulators are low enough to work topically (in theory).
I've elaborated on the therapeutic promise of SARMs in a hair loss prevention context before, and I have already seen this in real life application.
The binding affinity of most SARMs are also significantly better than CB-03-01.
With all that being said CB-03-01 is the only topical antiandrogen that is currently being developed for hair loss prevention and has a growing amount of safety data for us to refer to.
For most people, the obvious choice of which topical treatment to use would be the one with the most safety data on it.
Based on what I've seen, CB-03-01 may be moderately effective for some individuals at holding their ground.
And realistically, you can't really expect a whole lot more than that from a topical antiandrogen that doesn't affect the endogenous hormone profile at all.
This is the kind of thing you would start taking before you notice hair loss to maintain, not something you would implement once you've receded several Norwoods and have severe diffuse thinning.
Deploying CB-03-01 before hair loss gets too severe may be sufficient in maintaining perfect hair with minimal side effects for years, if not decades.
A proactive approach needs to be taken to hair loss prevention, not a reactive approach once you've already experienced significant amounts of miniaturization.
Using this as a reactive approach to make up lost ground will likely yield less than satisfactory results because it is a prevention/maintenance drug.
Facilitating significant regrowth would require more intensive protocols with less favorable side effect profiles.
Price is one CB's of the biggest limitations right now.
There are very few companies selling it, and the ones that are have it priced several times higher than alternatives that are just as effective.
In addition, CB-03-01 requires an even higher daily dosage than the cost-effective alternatives, making it even more cost prohibitive.
The results of the human trials have shown that a minimum of a 7.5% strength solution would be needed, and it may even need to be applied twice per day to achieve sufficient maintenance.
That's 150 – 450 mg of CB-03-01 per day just to potentially achieve maintenance (depending on how much solution you need to use to get full scalp coverage with each application).
You could easily end up spending over $100 – $300 per week just to use the minimum effective dosage of CB-03-01, and still be underwhelmed with your results.
With that being said, once Breezula is available as an FDA approved treatment, perhaps the price will become less of a concern, but as of now it is just too cost prohibitive for most of us at the dosage needed to yield sufficient hair loss prevention.
Preventing loss is what should be expected of an effective antiandrogen.
It seems like in less aggressive cases CB-03-01 is mildly effective in doing that.
For many individuals though, it is not turnkey monotherapy option.
Does that mean its useless?
No, not at all.
It is definitely a better line of defense than nothing, that's for sure.
For individuals with more aggressive loss who have implemented CB-03-01 with subpar results, they would likely need to add other compounds into their protocol.
Complementary compounds to CB-03-01 for a more comprehensive protocol may include things like 5-alpha reductase inhibitors, PGD2 inhibitors, PGE2 agonists, potassium channel openers, Non-Steroidal SARMs, Steroidal SARMs, antiandrogens, other bioidentical sex hormones, etc.
CB-03-01 (or another formidable topical antiandrogen) used in conjunction with a 5-alpha reductase inhibitor, Minoxidil and a Ketoconazole shampoo will be effective in staving off hair loss for decades for many individuals.
Is it the most effective option?
No, however, it is tried and true and has a fairly predictable side effect profile with lots of human clinical and anecdotal data to refer to.
Keep in mind, treatment options can have a compounding effect in protection, and there can be many pathways to address.
For example, if you are just using Finasteride to inhibit 5-alpha reductase, sure you will knock out a fair chunk of your systemic and scalp DHT, but what are you doing to protect you from the rest of the unaddressed DHT?
And what are you doing to address the massive spike in scalp Testosterone that comes along with inhibiting the 5-alpha reduction of Testosterone into DHT?
Despite many treatment options being marketed as “treatments”, the reality is that most of them just address one pathway in the body, and can even precipitate other issues that then need to be addressed with adjunct treatments.
This is why topical antiandrogens have such therapeutic promise.
Clinical Trial Results
Cassiopea recently published the results of their 12 month clinical trial [R]:
Six Month Interim Analysis Efficacy Results
|Primary Endpoints at 6 months (interim analysis on 375 subjects)||Clascoterone|
|Mean changes from baseline TAHC||13.0134||12.2109||20.7879||11.5182||-0.1114|
|P value (vs. baseline)||< 0.0001||< 0.0001||< 0.0001||< 0.0001||0.9660|
|P value (vs. vehicle)||0.0003||0.0010||< 0.0001||0.0017||—|
|Favorable HGA (+1, +2, +3)||56%||58%||62%||61%||49%|
As you can see, favorable hair growth assessment (HGA) improved in all CB-03-01 treated groups compared to the vehicle treated group.
With a lack of side effects and a high level of tolerability, CB-03-01 looked very promising at the six month mark.
However, the twelve month mark showed less encouraging results.
Twelve Month Analysis Efficacy Results
|TAHC Per Protocol (344 subjects) At 12 months|| Clascoterone|
|Mean changes from vehicle TAHC (n.)||10.2||13.8||14.3||12.7|
|P value (vs. vehicle)||0.0087||0.0006||0.0003||0.0016|
|HGA Per Protocol (344 subjects)|| Clascoterone|
|At 12 months|
|Favorable HGA (+1, +2, +3)||60.8%||60.0%||61.8%||56.1%||50.0%|
Per Protocol (344 subjects)
At 12 months
|Mean changes from vehicle TAHW (µm)||521.1||615.0||762.5||658.8|
|P value (vs. vehicle)||0.0105||0.0034||0.0003||0.0018|
As you can see, the vehicle increased from 49% > 50% favorable HGA at 12 months, whereas 12 months using the highest dosage of CB-03-01 once per day caused a 4.9% drop in favorable HGA.
That means that the group who was not treated with anything were perceived to have better results than the group that was using a high dose of CB-03-01 once per day by the twelve month mark.
Now, keep in mind that favorable HGA only represents the opinion of the patient on hair growth, expressed with a questionnaire.
It is subjective, but at the end of the day, it is not rocket science to look at before and after pictures of your hair and see if you are happy with your progress or not.
Also, this is only one dosage arm, but still, it's not overly promising, unfortunately.
Twice per day dosing of the highest CB-03-01 concentration dropped 0.2% by the twelve month mark, which could be argued to be representative of maintenance, but with how expensive this stuff is (as of now) using a 7.5% strength solution twice per day is not really realistic, let alone once per day.
With all that being said, even if maintenance is achieved with a complete absence of side effects, that would be considered a win for a topical antiandrogen candidate.
Binding Affinity Of CB-03-01 Vs. RU58841
CB-03-01 binds to the androgen receptor with approximately 100-fold lower affinity than DHT [R].
A common feature of pure antiandrogens, such as Hydroxyflutamide and Casodex, is their relatively weak binding affinity for the androgen receptor, 50–100 times less than that of Testosterone.
However, RU58841 binds to the androgen receptor with an equivalent affinity to Testosterone (ka = 1.1 nM) [R].
DHT has a binding affinity of 0.25-0.5 nM for the human AR, which is about 2-3 times higher than that of Testosterone [R].
By extension, we can estimate that CB-03-01 binds to the androgen receptor with approximately 40-fold lower affinity than Testosterone.
Consequently, we can assume that RU58841 has a binding affinity 40 times higher than CB-03-01.
Topical RU58841 also showed no detectable abnormalities in body weight, hematology, and blood chemistry tests, serum levels of testosterone, dihydrotestosterone, and luteinizing hormone during examination [R].
My CB-03-01 Review
At the end of the day, I do believe that CB-03-01 is promising, however, I do not believe that it is going to be a turnkey monotherapy solution that is effective in staving off hair loss in anyone with even moderately aggressive androgenic alopecia.
I also believe that there are more cost-effective alternatives that already exist that are also more effective at preventing hair loss.
With that being said, we still have to see if further research in the future reveals more promising data and if it becomes less cost prohibitive.
As of now though, I do not think that it is better than alternatives that are already available to us.