An Overdue Aclaris Update

Update: February 29, 2020

Aclaris Exits Hair Loss Business

Recent rumors are, unfortunately, very true. Several days ago, I contacted Aclaris Therapeutics’ Head of Corporate Strategy Mr. Michael Tung. I asked him for any update on their androgenetic alopecia (AGA) JAK inhibitor product. His short and succinct response was as follows:

“We exited all of that unfort”.

I am disappointed, but was expecting this bad news. Their pipeline page no longer even shows any products to target AGA or Alopecia Areata (AA). Last year, they were searching for a partner to help further develop their “investigational compounds” ATI-501 (oral) and ATI-502 (topical).

Sorry to reader “nasa_rs”. However, not a big surprise after the past year of limited information releases by Aclaris regarding their alopecia products.

March 18, 2019

Aclaris JAK Inhibitor Trial Update

I used to cover Aclaris Therapeutics and its topical JAK inhibitor product for androgenetic alopecia fairly regularly. However, there have been very few significant recent updates.

Today morning, Aclaris released a summary of its FY 2018 results. The most relevant part for us concerns the ATI-502 topical Janus Kinase (JAK) 1/3 inhibitor product for AGA. They also seem to name this same product as AGA-201 and ATI-50002 in other references.

Per the latest news, Phase 2 open-label clinical trials for ATI-502 (a topical JAK1/3 inhibitor) involve 31 patients with AGA. Interim 6-month data are expected in the second quarter of 2019, while comprehensive 12-month data will be realized in the second half of 2019.

So by the end of this year, we should finally have at least some idea on whether JAK inhibitors can at least somewhat help patients with AGA (aka male pattern hair loss).

The trials will measure both safety and efficacy.

We already know beyond a doubt that JAK inhibitors significantly help people with the less common alopecia areata. As well as thos with its various related forms (alopecia totalis and alopecia universalis).

Topical Finasteride for Hair Loss

I originally wrote this post on topical finasteride in June 2014 and update it every year.

Less Systemic Absorption of Topical Finasteride

A new study on topical finasteride spray solution concluded that it causes improved hair growth to the same degree as oral finasteride. Moreover, the topical version led to markedly lower systemic exposure.

Maximum plasma finasteride concentrations were >100 times lower with topical finasteride spray solution.  Mean serum DHT concentration was lower (34.5% vs 55.6%), with topical versus oral finasteride. There is a smaller risk of systemic adverse sexual side effects with topical finasteride.

Almirall ALM12845

It finally looks like Spain-based Almirall will release its ALM12845 topical finasteride in 2020 or early 2021. Note that this product was previously known as Polichem’s P-3074. Almirall purchased Polichem in 2015.

The company filed for a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in September 2019. The ALM12845 product is described as a cutaneous spray solution for the topical treatment of men with androgenetic alopecia. First national phase approval is expected in 2020 or early 2021. I am not sure if they will be able to get FDA approval to market in the US as yet. The pipeline chart below only shows an EU flag:

Almirall ALM12845 Topical Finasteride.
Almirall ALM12845 topical Finasteride.

Topical Finasteride for Hair Loss

Recent reports suggest that topical finasteride results in similar increases in hair count compared to oral finasteride. Topical finasteride is typically compounded in gel or solution form. The oral version can come in pill, capsule or tablet form. It is hoped and likely that the topical version has fewer side effects than the oral version.

2018 update: A systemic review of topical finasteride shows consistent reduction in hair loss. Both scalp and plasma DHT levels decreased significantly.

Topical Finasteride
Topical finasteride for hair loss.

The manufacturer of Propecia (Merck) applied for a patent for topical finasteride in 2002. However, the company has to date never tried to develop an actual product. This is all the more surprising when considering that Propecia has been getting significant negative publicity of late. Many users suffering from long-term sexual side effects have filed a class-action lawsuit against Merck.

Polichem’s P-3074

I am writing this post today because an important clinical trial/study for P-3074 was just completed in Switzerland. 2019 Update: P-3074 final trial results are now published.

P-3074 is a new topical finasteride solution with hydroxypropyl-chitosan as the film-forming agent. The study was funded by Swiss company Polichem, which primarily specializes in dermatological and gynecological products.

The interesting thing about this study is that four different doses (ranging from 0.25 mg to 1 mg) of topical finasteride were tested. The study entailed 32 human participants, with 8 of those 32 getting a placebo dose. One negative thing about the study is that only a 7-day dose of the topical P-3074 solution was administered. There will therefore be no long-term measurement of the effectiveness of P-3074. It will be interesting to see the results of this study regarding yet another new hair loss product.

Note that a similar trial (although at just one dosage level of 0.25 mg per day) for P-3074 was conducted in the past. Its findings were presented last year at the 7th World Congress on Hair Research (WCHR 2013). The conclusion of this trial was quite significant:

“These findings show that DHT concentration in the scalp, after 7-day treatment course of P-3074 once daily, was more reduced (about 40%) than after 1 mg oral finasteride administration for the same treatment period.”

Topical Finasteride Side Effects

The main reason that people are so excited about topical finasteride is because of potentially fewer side effects in comparison to oral finasteride. Serum dihydrotestosterone (DHT) inhibition in the blood is significantly less with topical finasteride versus oral finasteride. At the same time, scalp DHT inhibition will remain similar with both delivery mechanisms.

However, it should be noted that different formulations will result in different levels of DHT inhibition. It is therefore imperative to be very careful if you are purchasing this product from any compounding pharmacy. Some of the below collected sources indicate that sexual side effects will be less likely with topical finasteride. At the same time, hair growth benefits will be similar for oral versus topical.

References and Studies

There have been other studies done in the past that concluded favorable results from topical finasteride. For example, a 2009 study from Iran concluded: “the therapeutic effects of both finasteride gel and finasteride tablets were relatively similar to each other.” Nothing is mentioned regarding side effects in the abstract of that study.

A more recent 2012 study from Thailand concluded that a 3% minoxidil plus 0.1% finasteride lotion (“MFX”) was superior to just 3% minoxidil (“MNX’). There is also an increasing amount of new research on better ways to deliver topical hair loss drugs, especially via nanocarriers.

Update: April 2020 — A new study found topical finasteride to be more effective than topical 17α-estradiol in women suffering from female pattern hair loss (FPHL).

It should also be noted that the original Merck patent for Propecia has a number of sentences mentioning topical formulations as also likely being effective.

What I am really hoping for are future studies on topical dutasteride. The main reason for this, besides dutasteride’s superior results to finasteride, is that type I 5α-reductase isoenzymes are more prevalent on the scalp. Type II 5α-reductase isoenzymes are more prevalent in the prostate.

Finasteride primarily inhibits type II 5α-reductase, while dutasteride also inhibits type I 5α-reductase. I would therefore not be surprised if topical dutasteride’s superiority over topical finasteride is even greater than the superiority of dutasteride pills over finasteride pills. Hopefully, there will also be fewer side effects even after accounting for some systemic absorption via the scalp.

A few hair transplant surgeons have developed their own topical finasteride solution, usually in partnership with local pharmacies. If you happen to have heard more on this, please post in the comments section below this post. Some hair loss forum participants seem to have tried to develop their own topical finasteride or even topical dutasteride. Something I would not recommend. The science of topical medication delivery is a bit too complex for the vast majority of us to be experimenting with on ourselves.

Other Sources of Topical Finasteride

A number of clinics and many local pharmacies can already compound topical finasteride for you. However, such localized products will never be substantiated by clinical studies, as is the case with Almirall’s product. Moreover, a large company such as Polichem has devoted years of research in perfecting its drug delivery system. They also have to prove limited to no side effects from their product during the rigorous clinical trial phases.

Update: I got an e-mail from the Hasson & Wong clinic on June 17, 2014 stating the following:

“Dr. Hasson is prescribing topical finasteride to some of his patients and it is being prepared at a pharmacy close to our clinic. To date the results have been very similar to the oral finasteride.”