Category Archives: Dihydrotestosterone (DHT)

Winlevi, Acne, Cassiopea, Clascoterone, Dihydrotestosterone (DHT)

Winlevi: Cassiopea’s Breakthrough Acne Treatment

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I first wrote this post on Winlevi and acne in 2019 and am updating it again. Winlevi clascoterone 1% cream is a first-in-class androgen receptor inhibitor that can be used by both males and females. Also see my related posts on clascoterone based hair loss treatment Breezula.

Update: November 1, 2021 — Sun Pharma announces that Winlevi Clascoterone 1% cream is now available for sale in the US. To be used for the treatment of acne vulgaris.

August 1, 2021

Winlevi, Cassiopea and Sun Pharma

Winlevi (clascoterone cream 1%) will now be released in the US market in the fourth quarter of 2021. Official website here.

On July 26, 2021, Cassiopea announced that it was partnering with Sun Pharma in order to commercialize and market Winlevi in the US and Canada. On July 29, 2021, the company also released its first half 2021 results.

The US FDA approved Winlevi® (clascoterone cream 1%) in August 2020 for the topical treatment of acne vulgaris. This prescription drug is a topical alternative to Accutane and Spironolactone. It is an anti-hormonal treatment for acne that targets the androgen receptor. It works by reducing sebum production and scalp inflammation.

Many people will inevitably try to use Winlevi on their scalps for hair growth (via off-label prescription). This is not recommended by the manufacturer.

August 27, 2020

Winlevi Approved by the FDA to Treat Acne

Winlevi Clascoterone Cream 1% for Acne.
Winlevi Clascoterone Cream 1% Acne Treatment.

Cassiopea’s Winlevi topical androgen receptor inhibitor was just 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 US FDA is also reviewing a new drug application (NDA) for clascoterone cream 1% to treat acne.

More information from Cosmo Pharma (Ireland — COPN:SWX), which owns 45 percent of Cassiopea (Italy — SKIN:SW).

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.”

August 23, 2019

I have covered Italian company Cassiopea numerous times on this blog. Primarily due to its Breezula topical product for male pattern hair loss. Earlier this year, Cassiopea announced very good 12-month Phase 2 clinical trial results for Breezula.

Clascoterone and Acne

Cassiopea is also working on an acne product called Winlevi. Both Breezula and Winlevi are based on the same key ingredient: Clascoterone. However, the dosage in the latter is significantly lower at 1%. This acne product is almost ready to come to market per Cassiopea’s product pipeline.

Winlevi (Clascoterone) Pipeline.
Winlevi clinical trial and NDA filing schedule.

 

Earlier this week, Cassiopea made a major announcement. The company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking marketing approval for clascoterone cream 1% for the treatment of acne.

My Thoughts

Some interesting points in the press release and my thoughts:

  • Clascoterone cream 1% targets androgen receptors at the site of application. This inhibits the local (skin) effects of dihydrotestosterone (DHT). Apparently, DHT is a key driver of acne lesion development. Most people wrongly assume it is solely testosterone.
  •  This acne treatment product will be safe to use in both males and females.
  • If approved, clascoterone cream 1% will represent the first new mechanism of action in the treatment of acne in almost 40 years. Interestingly, if Breezula is approved for hair loss in 2021, it will be the first new topical or oral treatment for hair loss in almost 25 years.
Androgen Receptors, 5α-reductase, Dihydrotestosterone (DHT)

Destroying Androgen Receptors on the Scalp

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Recently, a reader and hair loss sufferer named “James K” sent me a very interesting e-mail pertaining to destroying androgen receptors. I have pasted most of his e-mail content towards the bottom of this post. Note that the androgen receptor is also known as NR3C4. Other options include looking into androgen receptor antagonists or androgen receptor silencing.

Destroying Androgen Receptors to Stop Hair Loss

Scientists know that male pattern hair loss (androgenetic alopecia) is caused by two factors that both need to be true:

  1. The present of high levels of dihydrotestosterone (DHT), a derivative of testosterone, in the bloodstream and scalp. 5-alpha reductase enzyme activity is what converts testosterone to dihydrotestosterone.
  2. The presence of a high level of androgen receptors on the scalp. Balding is a direct result of DHT binding to these receptors and then miniaturizing hair follicles. Many people can have high levels of DHT, but lack the androgen receptor (AR) gene. In those cases, they will not go bald. Finasteride drastically reduces  DHT from binding to 5α-receptors, resulting in increased hair growth for many people.

Follicle sensitivity to the damaging effects of androgens varies by person. The number of androgen receptors on a scalp’s dermal papilla cells also varies from individual to individual. Research seems to suggest that genetic predisposition to AGA is polygenic in nature and there is no individual gene that is responsible for male or female pattern hair loss. Note that some sources seem to term “androgen receptors” as “DHT receptors”.

On a related note, eunuchs who are castrated never suffer from male pattern baldness. Their DHT levels are negligible for their whole lives. Also of interest is the androgen insensitivity syndrome intersex condition. I bet some blog readers wish they had such a problem.

Going back to “James K”, his main question pertained to why scientists have not done more research into destroying the androgen receptors on the scalp?

Or somehow destroying the androgen receptor gene? While we await CRISPR based gene modification, other techniques such as NdAgo have so far been a bust or overhyped.

How to Destroy Androgen Receptors?

I will quote “James K” in this section:

“I think that a cure would be to destroy these androgen receptors on the scalp, thereby making their sensitivity to androgens irrelevant. Androgen receptors are heat-liable and can be destroyed by trypsin.

Trypsin is possibly safe for topical application, but has the side effects of pain and burning. From a study on rats, trypsin causes hair cells to die and regrow slower, as it changed their gene expression.

Perhaps a safer/weaker version of this can be developed for hair loss? What do you think?”

My Thoughts

I am surprised that there is not much more research on this available online. Is it possible to destroy androgen receptors on the scalp without killing the actual hair follicles? Or is this nonsensical, with the only future solution being a genetic one? i.e., deactivating the AR gene responsible for hair loss?

Update: Someone sent me a link to research on silencing the androgen receptor.