Category Archives: Topical Antiandrogen

Breezula, Androgen Receptors, Cassiopea, Clascoterone, Cosmo Pharmaceuticals, Topical Antiandrogen

Breezula Phase III Trials Begin

99 Comments

Update: September 13, 2023

Breezula Cosmo Pharma
Breezula from Cosmo Pharmaceuticals.

Breezula Phase 3 Trial Enrollment Opportunities

Earlier this week, someone I trust sent me a link in regards to a new androgenetic alopecia related clinical trial that is taking place in New Jersey, US. There are two very interesting keywords in the URL that I was sent:

https://cenexelresearch.com/hri/trials/androgenetic-alopecia/?utm_source=Facebook&utm_medium=Paid&utm_campaign=Cassiopea%20CB-03-01%2F37&utm_content=Dermatology

The shortened version of the link on CenExel clinical research organization (CRO)’s androgenetic alopecia page does not mention the involvement of Cassiopea (or its new owner Cosmo Pharmaceuticals). Neither does it mention any product name.

However, in my last update of this post in June, I mentioned that Cosmo is finally starting its Breezula topical anti-androgen Phase 3 clinical trials in the US and Georgia. A total of 750 males will be enrolled between the two countries. The trials will end in January 2025. I wonder if the above mentioned trials in New Jersey are for Breezula?

Please do not bombard this company with calls and e-mails. It could ultimately even be some entirely new product, or a misread on my part. However, if you are serious and can make it to New Jersey regularly, think about signing up. Perhaps they also have a local residency requirement. Note that you have to be a male of 18 years age or older who has androgenetic alopecia.

I have written about Cassiopea/Cosmo/Breezula in well over a dozen past posts. Feel free to read all of them, going back to the very first one in 2014 when the product was known as CB-03-01. Its key ingredient is known as clascoterone, an androgen receptor (AR) antagonist. Similar to Kintor Pharma’s KX-826 (Pyrilutamide).

Update: June 29, 2023

Cosmo Begins Phase III Trials for Clascoterone (Breezula)

Cosmo Pharmaceuticals just announced the beginning of Phase III trials of clascoterone solution in males for the treatment of androgenetic alopecia (AGA). The name of this product is Breezula®  and it is a novel androgen receptor inhibitor. Trials will involve 750 patients in the US and Georgia.

The company’s acne product with the same clascoterone ingredient (but lower dose) is called Winlevi and is already available in the market. Actual Phase 3 clinical trial details for Breezula can be found here.

Key quote:

“If approved by the FDA, clascoterone solution has the potential to be the only topical androgen receptor inhibitor for AGA and the first drug with a new mechanism of action for the treatment of AGA in nearly three decades.”

Update: February 16, 2023 — Cosmo Pharma’s latest guidance states the following:

“Cosmo expects to have the first patient enrolled in the Breezula® (Clascoterone solution for androgenetic alopecia) phase III trial in males in Q1 2023.”

Also see Cosmo Pharma’s new page on Breezula. The company took over majority ownership of Cassiopea in December 2021 after being a part-owner for years (see bottom of this post).

Update: October 7, 2020 — Cassiopea (Cosmo Pharma) completed enrollment in its Phase II trials for female pattern hair loss. The 6-month study has enrolled 293 patients. The four-arm study will divide volunteers into four treatment groups: clascoterone solution 5% BID (twice daily); clascoterone solution 7.5% BID (twice daily); minoxidil solution 2% BID (twice daily); and vehicle BID (twice daily).

Before Breezula 2023, there is Winlevi 2021

Update: August 27, 2020 — Cassiopea’s Winlevi topical androgen receptor inhibitor has just been approved as an acne treatment by the US FDA. It is the first acne treatment with a new mechanism of action to be approved in 40 years. The key ingredient (clascoterone cream 1%) is the same as in the keenly awaited hair loss product Breezula. The latter will have a higher dosage.

CEO Diana Harbort quote:

Dermatologists have said targeting androgen hormonal activity in the skin is ‘the holy grail’ of acne treatment for both males and females.

I expect Breezula will not come to the market till 2023, assuming it gets final approval. However, some people plan to use Winlevi on the scalp, even though this is not recommended by the manufacturer.

Breezula Phase 3 Trials Delay

March 19, 2020

How things can change in just a few weeks. Breezula Phase 3 trials have now been delayed till 4th quarter 2020 or 1st quarter 2021. All due to COVID-19 (Coronavirus), which has hit Italy particularly hard. More information can be found in Cassiopea’s 2019 Annual Report which was released today.

The Clascoterone female pattern hair loss Phase 2 trials are on track to finish enrollment in 2Q 2020. Trials should be completed by year-end 2020. However, delays are still possible depending on progression and recurrence of the current pandemic.

Quote from the accompanying pdf:

“As part of the process in the NDA review, the FDA amongst other, also inspects the facility in which Clascoterone cream 1% is manufactured. Clascoterone cream 1% is planned to be manufactured at Cosmo Pharmaceuticals plant in Lainate in Italy. Given restrictions currently in place because of the COVID-19, the FDA had to postpone the inspection planned for March.”

Nevertheless, Cassiopea is still planning to release its Winlevi acne cream product by the end of this year.

Update November 13, 2019: Cassiopea’s women’s hair loss clascoterone solution Phase II trials starting soon in Germany.

April 16, 2019

Cassiopea (Cosmo Pharmaceuticals)

I have covered Italian company Cassiopea since 2014 (when it was called Cosmo Pharmaceuticals). The company is developing a topical anti-androgen hair loss product named Breezula (originally called CB-03-01). The chemical name for this product is Clascoterone. Note that Cosmo Pharma still owns 45 percent of Cassiopea.

Breezula will be available for both men and women. Several of my well known physician contacts in the hair loss world have told me great things about this product. Their feedback is based on what they saw at conferences or heard from colleagues.

Breezula Phase II Trials Very Successful

In July of last year, Cassiopea stated that the interim Phase II clinical trial results for Breezula were very positive. Today, they released twelve month Phase II trial results with the same conclusion:

Cassiopea announces very positive Phase II Twelve Months Results for Breezula® (Clascoterone) in treating androgenetic alopecia.

The presentation of the results is confusing, detailed, full of acronyms and somewhat open to interpretation. Note that “BID” in there stands for “twice per day” after conversion from Latin. Hopefully they release before and after photos at some point.

Also note that the previous 6-month interim report had 375 subjects, and the 12-month report has 344 subjects. The trial was conducted in Germany.

Breezula Target Area Hair Count Increase

Breezula Hair Count Increase
Breezula Hair Count Increase.

Best case result highlighted in yellow (14.3 new hairs per square centimeter, after 12 months of 7.5% BID clascoterone solution dosage). BID means twice per day.

Breezula Target Area Hair Width Increase

Breezula Hair Width Increase
Breezula Hair Width Increase.

Best case result highlighted in yellow (762.5 um width increase, after 12 months of 7.5% BID dosage).

My gut feeling is that Breezula will be at least as effective as Finasteride and Minoxidil.

Clascoterone Summary

Some key points from the above linked article from Cassiopea:

  • If approved, Breezula (Clascoterone) will be the first FDA-approved topical anti-androgen for the treatment of androgenetic alopecia.
  • Moreover, it would also be the first new drug approved for treating androgenetic alopecia since 1997. That year was when Propecia (aka Finasteride) was first approved to treat hair loss. That year was also when Tiger Woods first won the Master’s golf tournament. His 5th surprise victory in that tournament came this past weekend.
  • Based on these great results, Cassiopea plans to proceed with 6-month Phase III trials in men in the fourth quarter of 2019, after consultation with the FDA. The company is also going to start proof-of-concept trials in women.
  • Breezula works by blocking dihydrotestosterone (DHT) interaction with hair follicle androgen receptors.
  • Clascoterone does not interfere with testosterone and other hormones in male subjects. Libido and sexual behavior changes have so far not been observed in clinical trials. Moreover, due to its rapid metabolism and localized activity, Clascoterone (Breezula) does not produce any systemic side effects.

In the past, I used to often state that perhaps an initial cure for hair loss would entail the usage of a cocktail of products. Each working via different mechanisms and chemical or biological reactions.

It is looking likely that Breezula will be one of the main products in this cocktail.

Note that Clascoterone 1% cream to treat acne will be released by Cassiopea before Breezula. The acne product is called Winlevi.

Breezula, Cassiopea, CB-03-01, Topical Antiandrogen

Update on Breezula (aka CB-03-01)

81 Comments

In 2014, I wrote about a new yet to be released topical antiandrogen product called CB-03-01. Historically, antiandrogen products have usually been ingested orally and often led to adverse side effects. Early reports suggest that topical CB-03-01 has no significant side effects.

In 2015, the Italian company (Cosmo Pharmaceuticals) that was compounding CB-03-01 changed the product’s name to the unusual Breezula. Moreover, Cosmo itself was renamed as Cassiopea. I wrote about those developments here.

Breezula Phase 2 Results

Yesterday, Cassiopea released an interesting PowerPoint presentation summarizing 2015 and projecting the outlook for 2016. Edit: Link no longer working.

For us hair loss sufferers, pages 18-22 summarizing Breezula’s Phase 2 Proof of Concept (PoC) results is the most important section.

To summarize in brief:

  • 95 patients were enrolled in a double blind study that lasted for 6 months and ended in December 2015.
  • 31 patients were on Breezula 5%, 31 patients were on Minoxidil 5% and 33 patients were given nothing except a vehicle (i.e., placebo).
  • Of the 95 patients, 78 lasted till the end of the 6-month treatment period, and 73 of those were deemed to have completed the protocol without any violations. Of those 73 patients, 23 were on Breezula, 25 were on Minoxidil and 25 were on a placebo. A fairly even distribution.
  • 39 percent of patients on Breezula had at least some improvement in hair growth, compared to 36 percent of those on Minoxidil. 26 percent of patients on Breezula had at least some worsening in hair growth, compared to 16 percent of those on Minoxidil. Status quo was maintained in 35 percent of Breezula patients versus 48 percent of Minoxidil patients.
  • Later in 2016, Cassiopea will commence further dosing related trials for Breezula. I wonder if they will compare the effectiveness of higher doses to the effectiveness of the much more rarely used Minoxidil 15%?

I was pleased to see the results. Overall, Breezula seems as good as Minoxidil, and since the latter is not an anti-androgen, we can use both products topically on our scalp for two separate positive effects. Perhaps we can also add topical Bimatoprost and topical Finasteride to that combo later this year, and then we would have a quartet of topical products, each tackling a different mechanism of balding.

Future Release Date

Of course Breezula is still years from release (even if we assume they can speed up phase 3 trials like is the case in Japan, with newer regulations), but some people on hair loss forums are purchasing it illegally or even making it at home. An even more optimistic scenario is the addition of Samumed’s topical SM04554 to the mix whenever that comes out. It would be funny if in 2020, I started applying a quintet of topical products to my scalp and then suddenly a simple cure for hair loss came out that made all those topical products obsolete.

For younger people who have only been balding for a few years or less, such incremental developments are probably not too exciting. For those of us who have been following the hair loss industry for many more years, it is very pleasing to finally see new products arriving. It is ridiculous that there have only ever been two products officially FDA approved to tackle hair loss — 1) Finasteride and 2) Minoxidil.

***Note that on page 8 of the PowerPoint presentation they have labeled CB-03-01 as “Winlevi” and CB-03-11 as “Breezula”. Winlevi (for acne) and Breezula (for hair loss) contain the same key antiandrogen ingredient (a steroid belonging to the family of cortexolone derivatives), but in different formulations.