Like many medical discoveries, this one was made by accident. JAK inhibitors – a class of drugs used to treat conditions such as bone marrow cancer and rheumatoid arthritis – have been hailed as a miracle cure for hair loss. However, the truth is a little more complicated than headlines would suggest. Nevertheless, these drugs have great potential to help understand and even cure many forms of hair loss.
To skip to the June 2019 Aclaris Therapeutics update, click here.
JAK inhibitor alopecia areata studies
Last year saw a great many news headlines proclaiming a hair loss cure had been found.
The origin of these headlines was a trial from Columbia University Medical Center: 75% of patients treated with the drug Ruxolitinib experienced significant hair regrowth. In fact, average hair regrowth among patients was an astonishing 92%.
What many of these news reports failed to mention, though, was that the trial was for alopecia areata, not common pattern hair loss (androgenetic alopecia).
Alopecia areata is an autoimmune disorder characterised by circular spots of hair loss in seemingly random areas of the scalp. It is significantly less common than pattern hair loss, affecting just 0.1% of the population. For comparison, pattern hair loss affects roughly 70% of men and 40% of women at some point in their lives.
The 2016 trial wasn’t the first example of Ruxolitinib being used to successfully regrow hair. A smaller 2014 study produced equally spectacular results in patients with alopecia areata:
And a separate study – also published in 2014 – described a case where an individual was treated with Tofacitinib for psoriasis. Quite coincidentally, this patient also suffered from alopecia areata. Researchers were surprised to find the Tofacitinib not only cured his psoriasis – but his alopecia as well!
These two studies, published within a few months of each other, created a huge buzz worldwide. Both Ruxolitinib and Tofacitinib are Janus Kinase (JAK) inhibitors, which suggests JAK enzymes play an important role in alopecia areata.
A third JAK inhbitior, Baricitinib, also shows promise as a treatment for this hair loss disorder:
JAK inhibitors for pattern hair loss?
At least on the face of it, pattern hair loss is completely different to alopecia areata.
Whereas alopecia areata is an autoimmune disorder, pattern hair loss is largely believed to be caused by hormones – specifically dihydrotestosterone (DHT).
DHT is said to bind to hair follicles, causing them to get smaller and smaller until they stop producing visible hair. Nowhere in this explanation are JAK enzymes mentioned.
But the DHT explanation has a number of quite obvious problems. And there are a number of other differences between bald and non-bald scalps besides elevated DHT levels. One such difference is increased inflammation – a symptom that JAK inhibitors reduce.
Do you notice that your scalp tends to be slightly itchy in areas that are going bald? This is a result of increased inflammation. Shampoos that reduce this inflammation are popular among hair loss sufferers as they lessen this itchy feeling – but there is also evidence they might actually prevent hair loss as well.
Ruxolitinib and Tofacitinib prevent JAK enzymes from being released by inflamed cells. Of course, it’s a bit of a jump to say that JAK inhibitors will work for pattern hair loss just because they reduce inflammation, but there is definitely some link between pattern hair loss and inflammation.
And there’s more: recent research suggests JAK enzymes play an important role in hair follicle cycling. This raises the possibility of JAK inhibitor-based treatments for a whole range of hair loss disorders:
From telogen effluvium to chemotherapy-induced hair loss, JAK inhibitors such as Ruxolitinib and Tofacitinib may lead to important breakthroughs in hair loss research.
As for androgenetic alopecia – the most common hair loss disorder – the outlook also looks positive: Aclaris Pharmaceuticals are currently in the pre-clinical research phase of topical JAK inhibitors for this type of hair loss.
When will JAK inhibitors be available for hair loss?
Ruxolitinib and Tofacitinib are already available in oral form. However, they’re usually prescribed to treat bone marrow and blood cancers, not hair loss.
Furthermore, these drugs (particularly Ruxolitinib) can cause nasty side effects, such as:
- Thrombocytopenia (low platelet count)
- Anemia (low red blood cell count)
- Neutropenia (low neutrophil – a type of white blood cell – count)
- Increased risk of infection
- Weight gain
Basically, the oral JAK inhibitors available as of writing are not worth taking for the sake of improved hair. Furthermore, there is little evidence to suggest they make a significant difference – at least when it comes to pattern baldnesss.
This trial describes a 47 year old patient with alopecia areata treated with oral Tofacitinib. While this drug was effective at regrowing the hair lost due to this rarer form of hair loss, he still had a receding hairline when the hair grew back. This suggests oral JAK inhibitors are only effective at restoring hair lost due to alopecia areata, not hair lost due to the more common androgenetic alopecia.
It’s not all negative for sufferers of pattern baldness, though. The JAK inhibitor in development by Aclaris is applied topically to the scalp. Not only is this likely to reduce the nasty side effects described above, evidence suggests JAK inhibitors are far more effective for androgenetic alopecia when applied in this way.
As for when it will be available, though, it’s hard to say. It first has to pass the various FDA trial stages, which is likely to take at least four years – that’s if it makes it through at all.
Summary: JAK inhibitors hair loss
There’s no doubt that JAK inhibitors have been a huge breakthrough in the treatment of alopecia areata. The total hair regrowth commonly seen in the various trials of Ruxolitinib, Tofacitinib, and Baricitinib suggests we could soon have a complete cure for this rare form of hair loss.
But whether this translates into a cure for more common forms of hair loss remains to be seen.
My guess is that topical JAK inhibitors may well provide a useful adjunct to existing treatments. Inflammation undoubtedly plays a role in pattern hair loss, and there is evidence to suggest JAK inhibitors will tackle this. As an added bonus, JAK inhibitors look likely to extend the anagen (growth) phase of hair, making it look thicker and fuller.
June 2019 Update: Aclaris Therapeutics ATI-502
Aclaris Therapeutics recently released 6 month results for its Phase 2 trial of their ATI-502 JAK inhibitor product for androgenetic alopecia.
31 subjects (both male and female) with androgenetic alopecia took part in a trial which saw them topically apply the ATI-502 JAK inhibitor to their scalps twice daily. The results after 26 weeks (6 months) were as follows:
“The primary endpoint was the mean change from baseline in non-vellus target area hair count (TAHC) at week 26. The overall change was an increase of 8.6 hairs/cm2. TAHC increase was 15.3 hairs/cm2 in female subjects and 5.6 hairs/cm2 in male subjects. […] Based on these endpoints, investigators rated 73% of subjects (16/22) as experiencing increased hair growth, and 82% of subjects (18/22) rated themselves as experiencing increased hair growth. ATI-502 was well-tolerated. There were no treatment-related serious adverse events.”
You can read the full press release here.
Aclaris Therapeutics included before and after photos of ATI-502 for hair loss in an investor presentation that can be found here. A selection of these results photos is included below.