Breezula Phase III Trials Begin

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:

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.

Can you Reverse Grey Hair? New Updates.

My original post on a grey hair cure has gotten out of hand due to the constant new updates. I am therefore moving all the most recent grey hair reversal related developments into this post.

Grey Hair Reversal: Latest Updates

Update: September 6, 2023

A new South Korean company named YJ Lab is raising funds to start a large-scale clinical trial for its unique melanin restoration technology. The company recently developed a regenerative material that restores the pigment of grey hair. It re-activates damaged melanocytes and removes active oxygen in order to restore hair color. It has already conducted successful internal trials.

Grey Hair Reversal Research
New grey hair reversal technology. Source: YJ Lab.

Interestingly, YJ Lab is developing a specially made comb equipped with its refillable solution. Consumers can then conveniently apply this melanocyte regeneration material into the scalp.

Update: June 3, 2023

A very detailed new study from China in regards to the genetics of hair greying with age. One of the past sources they mention is the important hair genes study from Adhikari that I covered in 2016.

Update: May 22, 2023

Per a new study from Takahiro Suzuki et al, topically applied Rapamycin could reverse grey hair via mTORC1 inhibition. Rapamycin elevates the production of melanin and pigmentation. I covered rapamycin in my post on autophagy.

Update: April 19, 2023

Cause of Grey Hair may be Stuck Cells

The has been yet another breakthrough on finding the reason behind hair going grey. Scientists from New York University (NYU) found that melanocyte stem cells (McSCs) stop roaming around the follicle and become fixed or “stuck” in limbo as we age. As a result, they fail to mature into fully-fledged melanocytes that give hair its pigment.

The scientists conclude that modulating McSC mobility may represent a new approach for the prevention and even partial reversal of hair greying. The study lead investigator was Dr. Qi Sun and the senior investigator was Dr. Mayumi Ito, who I have mentioned before in this post. I like her quote in Guardian:

“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for greying and loss of hair colour.”

Update: March 31, 2023

An interesting one-off case of a male patient from Oman who got cyclosporine A induced hair repigmentation in his scalp, moustache and beard hair. Make sure to also read my past post on cyclosporine and hair growth.

Update: December 29, 2022

The Thymus Gland and Reversing Grey Hair

A new article on anti-aging has several items of interest in relation to grey hair reversal. A 72-year-old scientist named Gregory Fahy injects patients (as well as himself) with recombinant human growth hormone in order to rejuvenate the thymus gland. This could help reverse aging to some extent. Dr. Fahy is described as “having thick dark brown hair and being in enviable shape for a guy of pension age.”

Hair Darkening
Dr. Fahy’s patient with hair darkening and repigmentation.

One 70-year old patient named Hank Pellissier claims that “his hair, previously white, began growing in brown”. Note that Dr. Fahy’s prescribed regimen also includes dehydroepiandrosterone (DHEA) and Metformin. More details can be found on his company website and via their clinical trials page. Also of interest, Dr. Fahy showed several of his before and after patient hair repigmentation photos at a Ted Talk in 2020. See after 13:20 mins in this video.

Update: June 22, 2022

Gene Therapy

A new gene therapy treatment for a rare genetic disease (cystinosis) resulted in major hair darkening as a side effect. Four of the five patients have gotten significantly darker hair, and the fifth just started re-growing his hair post treatment. Of note, this gene therapy entails modifying blood cells, and only changes the DNA of a small fraction of the patient’s cells.

Update: May 2022

 Nicotinamide Mononucleotide (NMN)

An interesting new video on NMN potentially reversing hair greying and skin aging. Do note that both the interviewer and interviewee are involved in the sale of NMN products. The viewer comments in there are very interesting. Make sure to also read my popular post on NAD and NMN supplements.

Update: May 2022

Minoxidil and Reversing Grey Hair

Well known dermatologist Dr. Rodney Sinclair (a big proponent of oral Minoxidil) said the following in a new Reddit AMA:

“I have seen hair darkening with minoxidil in my patients.”

Moreover, on Reddit, I have read a few posts from people stating that oral Minoxidil caused their grey hair to become dark again. In November 2022, one person even posted that after just one month of 2.5 mg/day oral Minoxidil use, his chest and beard hair become dark again. In my other grey hair cure post, I also discuss topical Minoxidil causing grey hair reversal in some cases.

Update: February 2022

Hair Graying Regulators Beyond the Hair Follicle

A really interesting study from China analyzes hair graying regulators both within and outside the hair follicle in causing the depletion and dysfunction of melanocyte stem cells (MeSCs). Emerging evidences shows that nerves, adipocytes and immune cells outside of the immediate hair follicle environment (bulge, bulb and dermal papilla) also play important roles in the regulation of MeSCs.

Update: June 2021

Stress and Premature Greying

A new experiment mapped human hair greying in relation to recent life stress events. I am very skeptical about stress causing premature hair greying in most people. I have devoted a whole section to this popular subject in the second half of this post.

Note that in 2020, scientists from the US and Brazil also found that excess stress can turn pigmented hair white. Moreover, when cyclin-dependent kinase (CDK) protein was suppressed in mice, their fur did not change color.

Update: April 2021 — Harvard University scientists and a team from South Korea are developing a treatment for grey hair using pigment stem cells in hair follicles.

Grey Hair Reversal
50 percent of grey hair is re-pigmented after dupilumab treatment. Before and after at 16 weeks. Source: The Journal of Dermatology.

Update: September 2020 — Japanese scientists discovered an unexpected side-effect of dupilumab: reversal of hair graying. Dupilumab is a dual inhibitor of interleukin 4 and interleukin 13. It is used to treat allergic diseases such as eczema, asthma and nasal polyps.

Update: August 2020 — Make sure to listen to this interesting podcast on reversing gray hair.

Update: June 2020 — Chinese scientists found re-pigmentation of hair in a majority of Alzheimer disease patients after prolonged cholinesterase inhibitor therapy.

Hair Repigmentation
Hair repigmentation after Ustekinumab. Source: Ann Dermatol. 2021 Jun;33(3):300-301.

Update: June 2020 — South Korean researchers presented the first case of Ustekinumab-associated hair re-pigmentation. Ustekinumab is a monoclonal antibody medication that targets interleukin 12 and interleukin 23. It is used to treat Crohn’s disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis.

Update: April 2020 — A new synthetic melanin nanoparticle coating method was deemed as a safer, nontoxic and longer lasting way to dye hair.

Update: March 2020Eirion Therapeutics had its patent for a grey hair treatment published. It entails using plasminogen activator inhibitor 1 (pai-1) inhibitors to prevent hair graying. Eirion’s pre-clinical product candidates for hair loss and grey hair prevention are ET-02 and ET-03.

Update: January 2020

Not Irreversible

A review of medication-Induced repigmentation of grey hair:

“As evidenced by the many cases of gray hair repigmentation in the literature, the development of gray hair may not be an irreversible process. Gray hair is a natural course of aging; however, it may not be an inevitable or permanent process.”