CB-03-01 - new antiandrogenic

[baldnotbeautiful]

so its not worth buying from Iron dragon then?

Any word on if this stuff degrades when mixed like RU does? Or is it ok to buy a pre-mixed solution like this?

[Conpecia]

Can everybody posting about fin, propecia or whatever continue your debate on another thread which is labelled fin or prophecia??? Stop infesting these threads with your useless info that doesn't belong here. It becomes impossible to understand and follow these new products when 20 out of 25 pages have become a heated exchange between a few of you about the same old crap.

The moderators need to step in at some point, clean up some of these threads so they're actually relevant.

i mean i agree with this but wtf do you expect us to do? if someone asks why i'm considering cb and i tell them it's because of propecia sides, how am i supposed to get that info across? it's a problem of the forum's format. no pm's, no shoutbox, no way to write on someone's profile. doesn't give us many options.

i do agree that moderators should be able to come in and clean up old conversations that are off-topic. good luck getting that pushed through though.

[simba]

Skin usually has a 500 dalton tolerance, 400 is much lower, some may have issues with it but I think on the scalp where skin is thinning along with the hair, it should make it fairly easy regardless of vehicle. Dermarolling should only increase absorption.

How do I go about dermarolling with the purpose of increasing absorbtion? Do I roll and then apply the CB straight away or do I wait until the day after.

[simba]

Emailed Iron-Dragon to inquire what vehicle they will be using for their CB-01-03 and they responded:

50% propylene glycol / 50% ethanol

Just an FYI for those that are curious on what their vehicle will be. Isn't this the vehicle others have tried here and failed??

I just realized this probably wont be a problem.

Cant we just buy some Oleyl and mix it into ID's solution?

[hellouser]

I just realized this probably wont be a problem.

Cant we just buy some Oleyl and mix it into ID's solution?

Adding Oleyl to their premixed solutions lowers the concentration of the CB dosage. Also, have they even stated how much CB theyre giving away in total at $45?

[simba]

Adding Oleyl to their premixed solutions lowers the concentration of the CB dosage. Also, have they even stated how much CB theyre giving away in total at $45?

But isn't it the absolute amount that matters, so it'll be diluted but we can just apply more (and really, even if adding oleyl makes cb half as effective, that's still better then fin)

[yan]

Just realised that there is a slightly newer presentation on cosmo`s website.

Alopecia trial amendments due to change in formulation...

Next Milestone:

• POC alopecia $ 10 m (expected H1 2015)


http://www.cosmopharmaceuticals.com/..._Road_Show.pdf - page 28

But those points are listed under: CB-03-01 in 2012 and onwards

This could also mean that the change in formulation happened last year.

[yan]

Does anyone of you expect some new informations regarding the vehicle / efficacy from cosmo?

In my opinion, we have to wait until early 2015 to be really sure that there is a vehicle that works and shows similiar results like those from cosmo in 2011 with iontophoresis...
Until then its trial and error... But even in 2015, I don`t think they will publish the vehicle informations. At least we hopefully know by then that it works.

[adam k]

But isn't it the absolute amount that matters, so it'll be diluted but we can just apply more (and really, even if adding oleyl makes cb half as effective, that's still better then fin)

Indeed adding more solvent will reduce the molarity of the solution and as simba said to recieve the same amount of moles of CB more of the solution must be used.

Alternatively if one has some pure CB of the correct form then this dilution problem can be rectified with a simple calculation of how much more CB to add to bring the concentration back up. Of course for this to be viable we must know the exact concentration of the existing CB by Iron Dragon.

[Jazz1]

Iron dragon are legit guys I bought from then the pdg2 stuff my friend who tried fin failed to maintain hair. He recently about 2 months ago started iron dragon pdg2 and all his hairloss has halted, there's couple guys in hairloss help who have had the same. I can't speak for others but I can speak for my work friend as I recommended it and he's using it with success, unfortunatly no regrowth yet.

[yan]

Btw. just a side information:

Cosmo`s share price rose about 200% since 1 year. Why didn`t I buy some shares? Still no new treatment, but at least I would be rich now. :P

[HARIRI]

Btw. just a side information:

Cosmo`s share price rose about 200% since 1 year. Why didn`t I buy some shares? Still no new treatment, but at least I would be rich now. :P

You are Damn right about that yan. I wish I had extra savings to buy some Cosmo shares. CB with the right vehicle will do wonders for sure. Mamma Mia, Forza Cosmo :-)

[burtandernie]

Personally I think CB all panning out is way bigger and more important then anything else in the pipeline. All that other stuff just doesnt have history or results. We know androgens are a major factor maybe even a single way to completely prevent MPB forever but who knows we have never seen a strong enough androgen inhibitor. CB might be it and keeping hair cant be understated because if you keep the hair you dont need all that expensive futuristic stuff like hair multiplication

[HARIRI]

Here is a great explanation about CB from Iron Dragon :-)


Cortexolone 17-alpha propionate (CB-03-01): Peripherally Selective Anti-Androgen

Cortexolone 17-alpha propionate, also called CB-03-01, is a derivative of 11-deoxycortisone[1] with peripheral, selective anti-androgen activity. Published data demonstrate that cortexolone 17α-propionate possesses therapeutic potential as a topical anti-androgen for skin disorders such as acne, as well as androgenic alopecia (male pattern baldness). Cortexolone boasts equal or greater safety and potentially greater efficacy compared to retinoids used to treat acne, as well as a more localized and therefore potentially safer and more effective mechanism as compared to systemic 5-alpha reductase drugs such as finasteride and dutasteride. Though not currently FDA-approved, if FDA approval is granted cortexolone 17-alpha propionate will be the first commercially available topical anti-androgen[1].

Background and Timeline of Development

According to the manufacturer, Italian company Cosmo Pharmaceuticals, cortexolone “tightly mimics the profile of an ideal anti-androgen for topical use”[1]. The stated objective of the manufacturer is “to create a product for topical application to treat acne, male pattern baldness, and seborrhoea that does not have the side effects of products currently being taken in tablet form”[1] which presumably would include oral isotretinoin (Accutane) and antibiotics for acne, and 5-AR inhibitors such as dutasteride (Avodart) and finasteride (Propecia) for male pattern baldness.

Five clinical trials assessing the safety and efficacy of cortexolone 17-alpha propionate in European markets have been completed with favorable results, and non-clinical early data supporting the IND (investigational new drug) application was also deemed promising[2].

Per US FDA code, each individual disease or disorder claimed to be treated by a drug will require separate applications for the drug approval process. According to Cosmo, an IND application for acne was granted by FDA in the first quarter of 2012, with phase II escalating dose trials in process at the time of this writing[1]. While the future appears bright for cortexolone 17-alpha propionate as an alopecia drug, the IND process has not been initiated at this time; the manufacturer has stated their intent to apply for an IND for androgenic alopecia in 2014[1].

Anti-inflammatory and Anti-Androgenic Mechanism and Safety Profile and Rationale

Due to a common androgenic pathway between inflammatory acne and androgenic alopecia, cortexolone 17-alpha propionate is considered a promising drug for both disorders[3]. What is unique about cortexolone 17-alpha propionate is the peripheral and selective mechanism.

Cortexolone has good penetrative properties, making it suitable for topical use, and while effective locally it is metabolized into a harmless, inactive parent compound prior to circulating systemically:

“CB-03-01’s mechanism of action is based on the competitive activity between testosterone and DHT for androgen-receptors in the skin. CB-03-01 is devoid of systemic anti-androgenic activity, in as far as it does not inhibit gonadotropins hypersecretion, and has a moderate anti-inflammatory effect. In preclinical studies, CB-03-01 was shown to be rapidly metabolized by the skin to the parent compound cortexolone, which is a physiological steroid lacking anti-androgen activity and is completely safe. CB-03-01 has also been shown to have good penetration through the skin, making it the first anti-androgen suitable for topical application.”(emphasis added)[3]

The primary supporting study around which Cosmo bases their claims regarding safety and efficacy of topical anti-androgen therapy for acne was published in the British Journal of Dermatology in 2011.[4]

There are effective anti-androgens currently available, but they are not suitable for topical use and act in a systemic manner which, due to the pervasiveness of androgen activity and androgen receptors in physiological function throughout the body, results in a poor safety profile. As Cosmo CEO Mauro Ajani states, “drugs available for the treatment of acne are either not very effective or have substantial negative side effects”[3].

The recent manufacturer-funded studies and internal data are abundant, but there is also early peer-reviewed data that is illustrative of the comparative potency, and safety rationale, of cortexolone (CB-03-01) compared to other drugs:

“The aim of this study was to investigate the antiandrogenic activity of a new monoester of cortexolone, cortexolone 17alpha-propionate (CAS 19608-29-8, CB-03-01). Although the compound displayed a strong local antiandrogenic activity… it did not exhibit antiandrogenic activity in rats after subcutaneous injection, nor did it affect gonadotropins hypersecretion… As topical antiandrogen, the steroid resulted about 4 times more active than progesterone (CAS 57-83-0) and, when compared to known antiandrogen standards, it was about 3 times more potent than flutamide (CAS 13311-84-7), about 2 times more effective than finasteride …Its pharmacological activity seemed to be primarily related to its ability to antagonistically compete at androgen receptor level.”[5]

Androgen-Receptor-mediated Acne Mechanisms

The pathogenesis of acne vulgaris involves multiple factors, but local mechanisms mediated by androgens are known to play a significant role in the development of lesions:

“Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinisation, inflammation, and bacterial colonisation of hair follicles on the face, neck, chest, and back by Propionibacterium acnes.”[15]

The consensus is that each factor of acne vulgaris pathogenesis is involved in a complex interplay, and the resulting dysfunction often requires a multi-prong treatment approach:

“The multifactorial nature of the pathogenesis of acne includes increased sebum production, alteration of the quality of sebum lipids, inflammatory processes, interaction with neuropeptides and dysregulation of the hormone microenvironment, follicular hyperkeratinization and inflammation maintained by Propionbacterium acnes products within the follicle”[16]

The four primary factors – altered keratinization, bacterial colonization by P. acnes, increased sebum production, and inflammation – are often treated separately using different drugs; for example, oral isotretinoin to reduce sebum production, exogenous hormones (usually in women) to reduce androgen-receptor-mediated effects, topical retinoids or other drugs with anti-inflammatory properties, and systemic antibiotics for reduction of P. acnes colonization.

According to Lee et al, new data that shows that cultured sebum cells product inflammatory cytokines through an androgen-mediated pathway, suggesting that “DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne” [17].

Comparative Efficacy

In Treatment of Acne

In order to quantify the efficacy of cortexolone in treatment of acne, it was compared directly with tretinoin (Retin-A) 0.05% w/v in a randomized three-arm double-blinded controlled study with parallel treatment groups[3].

The trial entailed application of either compound (or control) to the facial region of sufferers of acne vulgaris, and lasted for ten weeks and compared total counts of two types of lesions, as well as overall severity of the acne using a standardized index[3]. Evaluations of each outcome were performed every other week[3].

According to the manufacturer’s website, “preliminary data of the trial showed that CB-03-01 met all clinical end points and was clinically superior to placebo and to Retin-A® in the treatment of facial acne vulgaris after 8 weeks of drug application” (emphasis added) [3]. The fact that cortexolone 17-alpha propionate not only took effect faster, but was more clinically effective than Retin-A in a large controlled trial demonstrates that its safety and efficacy profiles, taken together, are unprecedented.

The mechanism of action of cortexolone 17α-propionate is unique and suggests an exceptional safety profile compared to systemically dosed 5-AR inhibitory drugs currently used to treat androgenic alopecia.

Cortexolone 17-alpha propionate, Androgen Receptors, and AR-Targeted Treatment of Alopecia

Compared to the recently-demonstrated PGD2 mechanism, knowledge of the effects of androgen receptor agonism is not cutting-edge; the mechanism was first mentioned in published literature in the late 1980s [7], and early off-label use of 5-alpha reductase (5AR) inhibitor drugs finasteride (then Proscar, now also Propecia) and Dutasteride (Avodart) existed in the 1990s [8] prior to the approval of finasteride labeled for treatment of alopecia in 1997[9]. 5AR inhibitors prevent the local enzymatic conversion of testosterone into dihydrotestosterone, which is 2.4-10 times more potent in its action at the androgen receptor than testosterone depending on tissue and action examined [10]. However, they also reduce serum DHT levels, sometimes drastically, resulting in potentially undesirable effects[11].

5AR inhibitors are effective to prevent hair shedding when taken long-term by men with androgenic alopecia (AGA). However, lately there have been increasing concerns as to the short-term and long-term safety profiles of these drugs, both in civil courts and in the published literature:

“Men who suffered ongoing erectile dysfunction after taking prescription drugs to treat prostate problems and male pattern baldness will be able to pursue a class-action lawsuit against the drug maker, a B.C. judge has ruled.”[12]

“The significant reduction in DFI within 3 months of finasteride cessation and continued improvement suggests a causal link between finasteride and sperm DNA damage. We hypothesize that low-dose finasteride may exert a negative influence on sperm DNA integrity, resulting in increased pregnancy losses. We suggest that in infertile men using finasteride, sperm DFI should be measured in addition to semen parameters, and a trial of discontinuation of finasteride may be warranted.”[13]

The likely primary mechanism of most or all reported side-effects not due to nocebo-type effect is systemic action of 5-alpha reductase. When taken orally, 5AR drugs have systemic action and are in no way confined in their action to the peripheral (local) area of effect, namely the scalps of balding men. Topical applications of finasteride preparations may reduce systemic circulation, but will not prevent this issue, since, unlike cortexolone, the finasteride gel that absorbs into the dermal layer can still be circulated systemically in its active form[14].

The androgen-receptor-mediated mechanism is upstream of PGD2, meaning that it is hypothetically possible to reduce PGD2 levels to treat baldness without interfering with androgen levels. On the other hand, since PGD2 is likely associated in a general sense with inflammation, modulation of the androgen pathway may be an insufficient way to address baldness in some men if PGD2 elevation is caused by a pathway other than androgen receptor binding by DHT. Without more published PGD2 data, though, it is impossible to predict how future PGD2 inhibitor drugs may change the treatment landscape for AGA patients.

It is reasonable to state that the androgen receptor pathway of baldness is well-demonstrated, well-studied, and is an effective target for drug development in the interest of treating androgenic alopecia. Cortexolone, with a distinct yet similar mechanism (competitive inhibition/receptor inactivation, preventing DHT-binding) is a major step forward in addressing the major downside to 5AR inhibition as a baldness treatment because, if approved, it may be as effective as systemic, orally-dosed 5AR inhibitors, and would almost certainly be safer."

[HARIRI]

Check out this link:-

8 documents about Cortexolone 17-alpha propionate (CB-03-01)

http://www.biocentury.com/products/cb-03-01