Category Archives: Ruxolitinib

More Good News on JAK Inhibitors for AA; Mixed News on JAK Inhibitors for AGA

I was 50/50 about writing an entire post on JAK inhibitors, but in the end gave in due to the fact that I usually neglect the 1-2 percent of balding people who suffer from alopecia areata (AA) or the related conditions alopecia totalis and alopecia universalis.  For a majority of these people, JAK inhibitors clearly seem to be a cure assuming there are no long-term side effects.

There are also some new developments in the more controversial JAK inhibitors for androgenetic alopecia (AGA) patients discussion that are worth elaborating.  As is the norm when JAK related news comes out, the discussion in the prior post was taken over by this subject, in no small part due to “nasa_rs”.   I have let him run rampant in the comments section only because he came back after a lengthy break from this blog.  He will be allowed to continue posting the same stuff in the comments to this post, but thereafter I will become stricter.  It should be noted that despite his often repetitive comments, over the years “nasa_rs” has sent me some highly interesting and unique scientific information.  And recently, he was the first one out there to find the good news about Alcaris Therapeutics adding JAK inhibitor trials for AGA patients to their website’s pipeline page.  As a side note, if I recall, “nasa_rs” really did or does work for NASA…a bit of a scary thought.

Two New Studies Support JAK Inhibitors Working on Alopecia Areata (AA) Patients

In 2014, two groundbreaking papers discussed complete reversal of hair loss in alopecia areata patients.  While this was justifiably by far the biggest news of the year in the hair loss world (and widely covered by the global media due to the spectacular before and after patient scalp photos), there was one problem: the first of these two studies only involved one patient of Dr. Brett King (on arthritis drug tofacitinib), and the second only involved three patients of Dr. Angela Christiano (all three on bone marrow cancer drug ruxolitinib).

Two weeks ago, two new larger studies were released that solidified the above findings:

  1. Dr. Angela Christiano’s team from Columbia University in New York found that 75 percent of 12 patients with alopecia areata had successful hair regrowth while on ruxolitinib for between 3-6 months followed by a 3 month follow-up period.  By the end of treatment, average hair regrowth was 92 percent.  Perhaps the best part of the news: “The drug was well-tolerated in all participants, with no serious adverse events.”
  2. Even more significant, a much larger joint study from Stanford University (led by Dr. Anthony Oro) and Yale University (led by Dr. Brett King) found that of 66 alopecia areata patients treated with tofacitinib, 64 percent of patients had a positive response to treatment (and 32 percent achieved an improvement of over 50 percent after only 3 months of therapy). Side effects were generally mild.

From the above studies, it seems like ruxolitinib is better than tofacitinib when it comes to treating alopecia areata.  It remains to be see if results are even better when treatment is continued for a longer duration when it comes to either of the above two drugs. Note that a number of other newer JAK inhibitors will get approved and come onto the market in the US in the coming years.

Finally, for those who do suffer from alopecia areata, this is by far the best place in the internet to connect with others such as yourself.

JAK Inhibitors for Androgenetic Alopecia (AGA)

Some good news, some bad news and some in-between news here.

The Good:

  • First, from the 12 patient study article link I posted in the above section, Dr. Christiano still seems optimistic about JAK inhibitors working for AGA per the following quote:

“The CUMC research team plans to expand their studies to include testing these drugs in other conditions such as vitiligo, scarring alopecias, and androgenetic alopecia (pattern baldness) where they may also show efficacy. “We expect JAK inhibitors to have widespread utility across many forms of hair loss based on their mechanism of action in both the hair follicle and immune cells,” said Dr. Christiano.

The Bad:

  • However, Dr. King who in the past thought that it was worth testing JAK inhibitors (especially topical ones) for AGA now seems pessimistic according to this article:

“King said it is doubtful that Xeljanz (=tofacitinib) will work for the most common types of hair loss (such as male pattern baldness), which are not the result of an autoimmune disease.”

Note that both Dr. Christiano and Dr. King are listed as advisers to Alcaris Therapeutics in the conflict of interest section of the earlier linked 66 patient study summary page.

The In-Between:

  • One important bit of information on JAKs and AGA that never received the attention it should have (partly because I did not cover this subject much in recent months) happened a few months ago when Solomon interviewed Dr. Eddie Wang (who previously worked with Dr. Angela Christiano).  According to Solomon, Dr. Wang “rated JAKs success chance for AGA 5 out of 10“.  Dr. Wang seemed to think that JAKs could be reducing microinflammation in AGA patients and that could help hair growth.  I contacted him about how he came up with this 5/10 estimate, but he never responded.  I would put this development under “good news” if Dr. Wang had responded with a detailed answer.

Two (or More) Variants of AGA?

I have mentioned in the past that it seems like a majority of balding people have significant itching and dandruff in their balding regions, while some balding people have none of those annoyances whatsoever.  I always wonder if the people who have this itching and dandruff associated with their balding also have a significant inflammation (and maybe even autoimmune) component to their hair loss?  If topical JAK inhibitors do end up helping people with AGA, will those with significant itching benefit more?  I would not at all be surprised if researchers some day find that AGA patients can be broadly split into two main camps.

Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth

Finally, while I discussed this October 2015 study on this blog before as part of a lengthy post, I keep finding new items of interest in there.  I therefore thought it was worth pointing out the study again here in the hopes that some of the readers with a scientific background can give us more feedback on the contents.  Dr. Angela Christiano and Dr. Claire Higgins are both co-authors of this study. Some of the more interesting quotes:

“Hair growth after JAK-STAT inhibition mimics normal anagen initiation by activating the Wnt (Note: this is what Samumed is focusing on) and Shh signaling pathways.”

“JAK-STAT inhibition causes activation of hair follicle (HF) progenitor cells.”  (Note: also see this important patent filed in 2013: “Jak inhibitors for activation of epidermal stem cell populations”).

“Inhibition of JAK-STAT signaling improves skeletal muscle regeneration in aged mice.”

“Tofacitinib treatment promotes inductivity of dermal papilla (DP).”

“In human hair follicle assays, we show that JAK inhibition via tofacitinib treatment increases the growth rate of anagen hair shafts (skin grafts and organotypic culture assays) and enhances the inductivity of human DP spheres (neogenesis assays).  It is surprising that ruxolitinib treatment did not improve the inductivity of human DP spheres, despite the fact that it increased the rate of growth in the organ culture model. We postulate that down-regulation of proapoptotic signals in tofacitinib-treated spheres, which did not occur in ruxolitinib-treated spheres, may promote survival of DP cells, leading to enhanced hair growth in this assay.”

So JAK Inhibitors Could yet Still Cure Androgenic Alopecia!?

After my relatively long break, I had a lengthy post planned for today, but need to delay it due to a potentially great new development.

Summary of the Recent Past

In 2014, the biggest news in the hair loss world involved two separate developments related to two different JAK inhibitors (Ruxolitinib and Tofacitinib — search for both on this blog’s “Categories” menu as there are numerous posts on them) curing alopecia areata.  While those developments were incredibly exciting and groundbreaking, unfortunately the vast majority (>95 percent) of balding men and women suffer from androgenic alopecia (AGA) rather than alopecia areata (AA).  However, in 2014, Dr. Brett King did suggest that there was a possibility that JAK inhibitors could also cure androgenic alopecia during his interview with Spencer Kobren. In my own analysis, I have always stated that for many androgen related hair loss sufferers, perhaps there is also an inflammatory component (hence the increased itching and dandruff) and such cases could benefit from JAK inhibitors.

Thereafter, there was no news on this potential cure for AGA for a while, until in 2015 the one and only Dr. Angela Christiano posted results (albeit in mice) that suggested that JAK inhibitors could treat androgenic alopecia.  A must read post.  Moreover, this could occur via a topical (as opposed to oral) formulation of the two main candidate drugs: Ruxolitinib and Tofacitinib!

Thereafter, silence yet again for a long time.  Even worse, Christopher1 on hairsite stated that JAK inhibitors did not cure his androgenic alopecia.  He seems like a very reliable forum member over there so I was disappointed. However, the one good thing is that we do not know how accurately people are using JAK inhibitors at the moment since some are using off-label products, some are going to inexperienced physicians, some are trying topical experiments etc… so I still had some hope.  In any event, please be aware of the risks involved in these experiments and do not try them yourself.  Always see a physician before trying any drug to treat hair loss.

Thereafter, further contributing to the bipolar disorder and mood swings, on March 5 2016, a commentator named “Rick” posted an interesting comment on this blog that was largely ignored (and I am very surprised at this).  Although I hate to trust any one such commentator (especially in this particular case since he is also using Minoxidil as part of his treatment), I will still paste his comment below since it was missed by so many blog readers:

Just want you all to know that I have had very good success. With using tofacitinib 30% mixed with minoxidil. I have been doing this process topically for 3 months and have achieved full follicle growth! I will update you more in 30 days. And yes that is for male pattern baldness.

Perhaps “nasa_rs” has influenced me too much and I am looking for any positive signs?

Today

In any event the whole reason for this post is that today came news that Aclaris Therapeutics was buying Vixen Pharmaceuticals (Dr. Angela Christiano and Columbia University affiliated company).  See Form 8-K here.  At first, when I read a one paragraph news alert summary of this acquisition, I did not think much of this development since I had been to Aclaris’ website in the past and remember reading that they only deal with Alopecia Areata related drugs.

However, I then read a lengthier article about this latest acquisition and some things (see below in red font) clearly stood out:

“As a result of this transaction, Aclaris acquired worldwide rights to intellectual property licensed to Vixen by Columbia University covering the use of certain Janus Kinase (JAK) inhibitor compounds for the treatment of alopecia areata, androgenetic alopecia and other dermatological conditions.”

“The acquisition of the Vixen intellectual property and the licensed JAKPharm and Key Organics compounds solidifies Aclaris’ presence in the JAK inhibitor space and allows us to broaden our focus in hair loss to include androgenetic alopecia, often referred to as female or male pattern baldness,” said Neal Walker, President and Chief Executive Officer of Aclaris. [HT: Commentator Julian for pointing out that Mr. Walker is also CEO of Follica].

“We are delighted to enter into this agreement with Aclaris for the development of JAK inhibitors for alopecia areata, androgenetic alopecia, and other hair loss disorders,” said Dr. Christiano.”

In conclusion, welcome back nasa_rs.