It’s been over 20 years since the FDA last approved a pharmaceutical drug for the treatment of male pattern baldness (androgenetic alopecia). That drug was finasteride.
Meaning that in contrast to other fields of allopathic medicine – where new, cutting-edge drugs have been numerous – the field of androgenetic alopecia has stagnated.
But that could very soon be changing.
There’s a new drug in middle to late stages of clinical development.
It’s called clascoterone, and it promises to do something very similar to finasteride, but in a topical solution. And if we are to believe the manufacturer’s claims, there will be hardly any side effects.
Could this spell the end of minoxidil as the number one topical hair loss medication?
You will learn all about it in this article, including the very latest clascoterone news that you won’t find elsewhere.
Cassiopea: The company behind Breezula
Cassiopea are an Italian pharmaceutical company, publicly traded in the Swiss stock exchange since 2015. The company’s market capitalization (i.e. the total value of its outstanding shares) is currently sitting around $320 million USD.
That may sound like a lot. But it’s actually orders of magnitude less than even medium-sized pharmaceutical companies, whose market capitalizations are measured in billions – rather than millions – of dollars.
The company’s main focus is dermatological. They’re developing treatments for acne, genital warts and androgenetic alopecia.
Currently there are three products in the company’s R&D pipeline.
But the big one, the one that will determine Cassiopea’s future, is clascoterone.
Cassiopea own the rights to this drug at least till 2028, with the option to extend beyond that. And they are currently working towards getting it FDA-approved both as a liquid solution for hair loss, as well as a cream for acne.
The proposed brand names of clascoterone are Winlevi for the acne cream, and Breezula for hair loss.
What is Clascoterone, and How Does it Work?
In simple terms, it combats hair loss by blocking the androgen receptor (AR).
The AR is the target destination of the male hormone family, the so-called androgens.
Including the most potent androgen of all, dihydrotestosterone (DHT), which has been known for decades to be the molecule directly implicated in androgenetic alopecia.
DHT in the scalp binds to the ARs inside the hair follicles and activates them. Once activated, the ARs set in motion a cascade of biochemical reactions inside follicle cells, not least of which is the regulation of various genes’ expression.
Which of these biochemical reactions is responsible for the progressive hair follicle miniaturization that characterizes androgenetic alopecia is not yet clear. But we know for a fact that stopping the AR from being activated by DHT arrests the progression of male pattern baldness, at least for a majority of men.
When applied on the scalp, clascoterone interacts with the ARs within the hair follicles and surrounding sebaceous glass.
Clascoterone is a) similar enough to an androgen to be able to bind to the androgen receptor, and b) different enough so as to not activate it.
With the ARs in the follicles blocked, DHT is unable to bind to them and set in motion the slow but inexorable march to baldness. At least in theory.
Oral finasteride also works by blocking the action of DHT, albeit in a different way: it inhibits its synthesis, so there is altogether less DHT in the system. But the major problem with finasteride is the unwelcome side effects that it causes, by essentially throwing a massive monkey wrench in the endocrine system. These include, among others, impotence and loss of sexual desire.
In contrast to finasteride, it is very unlikely that clascoterone will cause any such problems. When applied on the scalp it is quickly metabolized to cortexolone, a molecule with a very weak antiandrogenic action.
So given that clascoterone a) is applied topically and b) rapidly metabolizes to less active compounds, there appears to be little potential for systemic absorption and serious side effects.
The Research to Date: Clascoterone R&D Timeline
Last year Cassiopea published the phase II results of their acne research in a peer-reviewed journal. You can find the paper here.
But the company has yet to submit any of their baldness research to peer review. As a result, we cannot scrutinize the research methodology in detail.
The only information we can go by at this moment in time (April 2020) are the company’s own press releases. So you can take what follows with a grain of salt.
Here’s the research timeline:
- February 2016: Cassiopea announces the first phase II results of its research on men with hair loss. The research compared a small sample of men who were allocated into three groups: clascosterone 5%, minoxidil 5% and an inactive placebo solution (control group).The study lasted 6 months, at the end of which the total increase in hair count in a 1 cm2 balding patch was recorded. The men on Breezula had an average increase of 12.7 hairs, compared to 18.8 for minoxidil. The drug also outperformed minoxidil (slightly) in terms of subjective patient satisfaction and investigator assessment.While these early hair count results suggest the drug is not as efficient as minoxidil, Cassiopea emphasizes that due to Breezula’s mode of action, final results may take longer to show than minoxidil (which we know starts to give good results after only 4 months).
- December 2017: Cassiopea completes recruitment for its phase II range-finding study. This is intended to compare three different strengths of Breezula solution and see which gives the best results. The strengths are 2.5%, 5% and 7.5%. In total, 404 males with mild to moderate androgenetic alopecia are enrolled, all of them in Germany.
- April 2019: The results of Cassiopea’s highly anticipated range-finding study are announced, and corroborate the earlier positive results.The 2.5% and 5% solutions were only given twice daily (BID), whereas some subjects received the 7.5% strength twice daily and others once daily (QD). After 12 months of treatment, the two main outcomes measured were a) hair counts in a 1cm2 balding area, and b) the patients’ assessments of the treatment efficacy, on a scale of +1,+2,or +3; signifying mild, moderate and marked improvement, respectively.
In the snippet below you can see the hair count results, as per the company’s press announcement:
Clearly, there was new hair regrowth with all 4 dosages. In the placebo group (not shown in the table) the men continued to lose hair as expected, meaning the hair count changes were negative.
This being a phase II study, there was no comparator arm with the established treatment, which in this case would be minoxidil. But we know from a multitude of studies that on this metric minoxidil typically gives values between 15 to 20+ hairs per cm2. Meaning it probably outperforms even the most efficacious dosage of clascoterone, namely the 7.5% twice daily, which registered an average value of 14.3.
With regards to the patient’s hair growth self-assessments (HGA), the results were less encouraging:
Cassiopea only gave the percentage of patients who were deemed to have any sort of regrowth, be it minimal, moderate, or marked (+1,2,3 respectively). The twice daily 7.5% group again had the best results, with 61.8% of men being assessed as having some hair regrowth.
But what jumps out from this table is the astonishingly high percentage of men (50%) who were on the placebo (vehicle) treatment and reported perceiving some regrowth. This high percentage does not square with the objective decreases in hair count that were carefully counted on these subjects’ scalps.
Whatever the reason behind this discrepancy, the difference in positive self-assessments between placebo-treated men and those in the strongest treatment arm stands at only 11.8%. Again, we find it difficult to be overly excited with these results.
In the same press release, Cassiopea reports that the medication has an excellent safety profile, with none of the patients experiencing serious side effects. There also appear to be no systemic effects on cortisol – in theory this could have been an issue because the chemical structure of clascoterone is similar to a steroid.
- November 2019: In a press release, Cassiopea announce they have recruited their first female patient in a phase II trial to examine Breezula’s efficacy as a potential treatment for female pattern hair loss. The company expects to recruit a total of around 280 patients with mild to moderate hair loss. Clascoterone at strengths of 5% and 7.5% will be compared against placebo and minoxidil 2%.
Recruitment is expected to complete in the second quarter of 2020, and the last patient to finish treatment by the end of 2020.
On the face of it, Cassiopea’s decision to invest in clascoterone as a hair loss treatment for women is risky, if not outright perplexing. As discussed above, clascoterone is an antiandrogen medication, meaning it works by blocking or interfering with the normal functioning of androgens.
But unlike males, the pathophysiology of female pattern hair loss is not clearly understood, and has not been conclusively linked to androgens. On the contrary, the medical literature paints a very sketchy, hit-and-miss kind of response to women treated with these medications. Which explains why to this date, minoxidil is the only FDA-approved medication for female pattern hair loss.
Does Cassiopea know something the rest of us don’t? One way or another, we will soon find out.
Dosage and Side Effects
As per the results of the range-finding studies, if and when clascoterone is approved, it is likely to be marketed as a 7.5% solution. And application will probably be twice daily, just as minoxidil.
Clascoterone appears to be relatively well-tolerated, and all the available data suggests there are no serious or unexpected toxicities. The most common side effects in acne patients are local skin reactions such as dryness, redness, hypersensitivity and acne. Headaches have also been reported.
Again, while the very limited information we have on side effects is encouraging, this could change in the future.
Like what happened with finasteride, where we slowly found out that while safe for most men, there’s a very small chance some may develop irreversible side effects. Though for the reasons we discussed above (topical application and weak metabolites) there is a good chance this will not be the case with clascoterone.
And, according to Cassiopea, loss of libido and erectile dysfunction, the two dreaded symptoms associated with finasteride, have not observed in men who take Breezula.
When Can We Expect Breezula to Hit the Market?
Having completed phase II trials, Cassiopea is currently working to finalize a special protocol assessment for its Phase III research program with FDA. This protocol assessment would signify that the FDA approves the trials’ design, methodology and statistical analyses, paving the way for the company to begin its phase III program in earnest.
Getting this special protocol assessment does not guarantee the drug’s eventual approval – this will always depend on the actual trial results, as well as finer trial details which do not go into the preliminary protocol assessment process. But it is, none the less, a very important milestone in the research program, and dramatically increases the probability of eventual approval.
So we seriously doubt Cassiopea will start the phase III trials before securing it.
If all goes well, expect the phase III clinical research to begin being organized towards the end of 2020, with the first patient recruited in early 2021. And, barring any persistent disruptions from the 2020 COVID-19 crisis, the trial should be completed by the end of 2022.
And who knows, you might be able to get your hands on some Breezula as soon as 2023!
For a tiny pharmaceutical company like Cassiopea, with a handful of staff and an equity (as of March 2020) of a few million dollars, the stakes are huge.
If clascoterone makes it past the phase III trials and gets FDA approval, its success is guaranteed. I won’t even hedge this statement with “almost guaranteed” or “all but guaranteed”.
Clascoterone for hair loss will sell. A lot.
It’s been over two decades since the FDA approved finasteride, and the medical community are clamoring for a new treatment option. Not to say anything of hair loss sufferers themselves. So at this point, any new drug that gets the coveted FDA-approval will be a commercial success, at least in the beginning.
Whether it will turn out be a success for the average user, at least in comparison to their existing pharmaceutical options, is a different story altogether.
The results we have seen so far do not allow us to be very excited. And while clascoterone does not appear to regrow more hair than minoxidil, it will certainly cost many times more. Between $100 and $200 per month, at least until the patent expires.