What is CB-03-01?
CB-03-01 (cortexolone 17α-propionate, CB-03-01) 1% cream is a topical androgen receptor inhibitor which has mainly been developed for the treatment of acne vulgaris (1). It is also presently being investigated in a large phase II clinical trial for the topical treatment of male-pattern baldness. CB-03-01 has been found to inhibit the androgen receptor regulated pathway (1). Also known as clascoterone, CB-03-01 is being developed by Cassiopea (a spin-off company from Cosmo Pharmaceuticals) and was initially commercialised as Breezula. Data from 2020 reveal that clascoterone is also being marketed as Winlevi for the management of acne vulgaris. CB-03-01 is thought to compete with DHT for its binding to androgen receptors in both the sebaceous gland and dermal papilla cells within hair follicles. The difference between Winlevi and Breezula is that Breezula is a solution that contains a higher concentration of the drug for the treatment of male-pattern baldness(2). In 2019, Cassiopea announced positive phase II 12-month results for their flagship product Breezula in the management of androgenetic alopecia. The phase II clinical trial recruited in excess of 400 participants in Germany and sought to evaluate the efficacy and safety of 4 different dosing regimens of CB-03-01 compared to vehicle agents in male subjects between the ages of 18 and 55 with mild to moderate male-pattern baldness. All participants were randomised to either apply CB-03-01 or a vehicle agent to balding areas of the scalp daily for 12 months. 5 treatment groups were analysed – 2.5% solution twice-daily, 5.0% solution twice-daily, 7.5% solution twice-daily, 7.5% solution once-daily, and vehicle solution twice-daily.
Researchers used target area hair count (TAHC) and hair growth assessment (HGA) score as the primary end-points of interest. For TAHC, statistically significant changes versus the vehicle agent were observed in all of the active treatment groups, with the most significant improvements observed in the 7.5% twice-daily group. These results are reassuring, as they demonstrate that CB-03-01 stops hair loss and accelerates hair grown in patients with male-pattern baldness.
In terms of safety, the publicised 12-month results are reassuring – there was a similar incidence of adverse events and local skin reactions in both the CB-03-01 groups and the vehicle agent group, with no treatment-related serious adverse events. Serum cortisol levels were also checked to verify that CB-03-01 is free from systemic steroid activity.
CB-03-01 versus Finasteride
Finasteride is a commonly utilised 5α-reductase inhibitor that increases hair counts and subjective hair appearance. CB-03-01 has been found to have the same effectiveness as finasteride. One 2019 study found that CB-03-01 inhibited androgen-receptor regulated transcription with a similar efficacy as finasteride (3).However, it bears mention that this was not a human study, but rather, an in-vitro study which looked at the effects of CB-03-01 on dermal papilla cells. Nevertheless, these results could be promising as CB-03-01 is a locally acting anti-androgen therapy which theoretically has a significantly lower likelihood of causing systemic side-effects such as finasteride.
CB-03-01 versus Dutasteride
Dutasteride is a potent 5α-reductase inhibitor which reduces DHT in up to 85% of patients after just 1 year of administration (4). Dutasteride has been shown to be more effective than finasteride in terms of the management of androgenetic alopecia (5). Finasteride and dutasteride work by inhibiting 5α-reductase so reduce the production of DHT. CB-03-01 works differently; it binds to DHT inhibitors so DHT can't bind to them. It works similarly to DHT receptor inhitibor RU58841 and ketoconazole.
CB-03-01 versus RU-58841
RU-58841 is a non-steroidal anti-androgen which was initially developed for the management of facial acne and androgenetic alopecia; also known as male-pattern baldness. RU-58841 works by binding to androgen receptors and directly inhibiting the effects of naturally produced testosterone and dihydrotestosterone (DHT). This leads to an overall anti-androgen effect in the body. American researchers studied the effects of RU-58841 in macaques and found that the topical application of this product resulted in significant increases in density, thickness and even length of hair in macaques with male-pattern baldness (6). RU-58841 has even been shown to outperform finasteride which is a 5α-reductase inhibitor that reduces the conversion of testosterone to DHT in the hair follicles. Indeed, Japanese researchers observed that RU-58841 is more effective than finasteride in the treatment of male-pattern baldness, and has the added advantage of not causing any systemic side effects (7).
CB -03-01 versus Minoxidil
It bears mention that currently, only minoxidil, finasteride and dutasteride are Food and Drug Administration (FDA) approved therapeutics indicated for androgenetic alopecia presently. From a regulatory standpoint, it must be emphasised that CB-03-01 has not been approved by the FDA for the treatment of androgenetic alopecia. Although Cassiopea’s clascoterone 1% cream has been FDA approved for the management of acne vulgaris (i.e., Winlevi), its higher-strength formulation of clascoterone that is indicated for androgenetic alopecia (i.e., Breezula) has not gained FDA approval. Hence, even though the preliminary results appear promising, and the safety data appear reassuring, it would be premature to draw conclusions about CB-03-01 as regards its performance. In fact, a review of the up-to-date scientific literature reveals that there is not a single clinical trial which compares CB-03-01 to the alternative agents discussed above – finasteride, dutasteride, RU-58841 and minoxidil. Hence, it is difficult to infer the cost-effectiveness of CB-03-01 in order to better inform consumers such as yourself about which product has the best ‘bang for buck’.
The main similarity that CB-03-01 could have with minoxidil, is that it could be used by women. In a 2021 announcement by Cassiopea, it was revealed that women less than 30 years of age who received a twice-daily application of 5% clascoterone solution demonstrated statistically significant improvements in TAHC at the 6-month interval.
Despite this similarity, Minoxidil probably outperforms CB-03-01. How do we know this? Data from the literature supports the fact that minoxidil results in 15-20+ hairs per cm2(8). Data published by Cassiopea in 2019 revealed that the highest dose of CB-03-01 (7.5% twice-daily) resulted in only 14.3 hairs per cm2. When we look at the subjective assessments by participants in the form of the HGA scores, the 7.5% twice-daily group had the best results, with about 62% of participants verbalizing that they experienced hair growth. While this may seem modest, it bears mention that 50% of the participants in the placebo group (i.e., vehicle agent) also expressed that they experienced hair growth.
Even though it has been 2 decades since the hair growth market has seen a new pharmacotherapeutic agent, it remains to be seen if CB-03-01 will outperform traditional and reliable agents such as Minoxidil. Phase III clinical trials are expected to be underway for Cassiopea in 2022 and the drug is expected to enter markets in 2023-2024. Nevertheless, preliminary data reveal that CB-03-01 may not be as effective as Minoxidil, and no cost data has been published by Cassiopea. Readers are advised to await randomised controlled trials which pit CB-03-01 against existing agents to better evaluate efficacy and cost-effectiveness.
1. Mazzetti A, Moro L, Gerloni M, Cartwright M. Pharmacokinetic Profile, Safety, and Tolerability of Clascoterone (Cortexolone 17-alpha propionate, CB-03-01) Topical Cream, 1% in Subjects With Acne Vulgaris: An Open-Label Phase 2a Study. Journal of drugs in dermatology : JDD. 2019;18(6):563.
2. Dhillon S. Clascoterone: First Approval. Drugs. 2020;80(16):1745-50.
3. Rosette C, Rosette N, Mazzetti A, Moro L, Gerloni M. Cortexolone 17α-Propionate (Clascoterone) is an Androgen Receptor Antagonist in Dermal Papilla Cells In Vitro. Journal of drugs in dermatology : JDD. 2019;18(2):197-201.
4. Evans HC, Goa KL. Dutasteride. Drugs & aging. 2003;20(12):905-16; discussion 17-8.
5. Arif T, Dorjay K, Adil M, Sami M. Dutasteride in Androgenetic Alopecia: An Update. Current clinical pharmacology. 2017;12(1):31-5.
6. Pan HJ, Wilding G, Uno H, Inui S, Goldsmith L, Messing E, et al. Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques. Endocrine. 1998;9(1):39-43.
7. Obana N, Chang C, Uno H. Inhibition of hair growth by testosterone in the presence of dermal papilla cells from the frontal bald scalp of the postpubertal stumptailed macaque. Endocrinology. 1997;138(1):356-61.
8. Blume-Peytavi U, Issiakhem Z, Gautier S, Kottner J, Wigger-Alberti W, Fischer T, et al. Efficacy and safety of a new 5% minoxidil formulation in male androgenetic alopecia: A randomized, placebo-controlled, double-blind, noninferiority study. Journal of cosmetic dermatology. 2019;18(1):215-20.
10% minoxidil with 0.1% finateride
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