Effective Alopecia Areata-Reducing JAK Inhibitor Dose, Identified

Alopecia Totalis and Alopecia Universalis - the more extreme iterations of the autoimmune disorder Alopecia Areata currently have little recourse in respect to treatments or therapies with a high success rate. Whilst some options exist, they tend to produce less than stellar results.

Although no hair loss solution has been clinically-proven to treat the mild form of Alopecia, which causes patchy bald spots to the scalp only - compared to the baldness induced by its more severe phenotypes - unlike the others, normal hair regrowth tends to resume naturally within 12 months in many cases. Furthermore, Alopecia Areata treatment for this basic form generally have a higher chance of accelerating hair growth.

Given how obvious these conditions are to others - with Totalis causing baldness of the head, and Universalis leading to the head and body rejecting all hair - they can have significant psychological effects on those affected, whether men, women or children.

It is for this reason, America's answer to the UK's MHRA - the Food and Drug Administration (FDA) - is lending its weight to the accelerated development of certain promising treatments for all forms of Alopecia Areata.

One of these is Concert Pharmaceuticals, CTP-543 - an oral JAK inhibitor drug to which it has granted Fast Track status.

Optimal CTP-543 dosage for hair regrowth now established

During the European Academy of Dermatology and Venereology (EADV) Congress in October 2019, representatives for Concert Pharmaceuticals gave an update from the on-going clinical trials into treating all forms of Alopecia Areata with CTP-543.

Data presented at the Madrid event went into more detail regarding the company's last update and showed that researchers had managed to achieve a 50 per cent relative reduction in Severity of Alopecia Tool score in patients at 24 weeks. These participants had at least 50 per cent hair loss of the scalp prior to starting their allotted medication.

The team had been investigating various dosages of CTP-543 in order to establish the optimum, during double-blind, randomised, placebo-controlled trials with adult participants. The contenders - 4mg, 8 mg or 12 mg - were all taken twice per day for the 24 week study duration.

By the end of the study, there were some impressive results for the higher doses. Whilst 21 per cent of the 4mg group saw their SALT score improve by a minimum of 50 per cent, almost half of all patients in the 8mg group (47 per cent) and just under two-thirds of patients in the 12mg group (58 per cent) achieved this. In contrast, 9 per cent of participants in the placebo group achieved the same.

For those patients who responded to the treatment, the two larger dosages also boasted average SALT score improvements of 78 per cent in the 8mg group and 86 per cent in 12mg group.

Patient Global Impression of Improvement surveys echoed these findings, with 58 per cent of patients taking the 8mg of CTP-543 twice-daily and 78 per cent of those in the 12mg group noting they believed their hairloss to be either “much improved” or “very much improved” at the 24 week endpoint.

James V. Cassella, PhD, the study author and chief development author at Concert Pharmaceuticals - who advised that, in addition to being effective, the drug had been found to be tolerable at all these doses - told the Healio Dermatology journal, “I believe we are seeing the strongest effect of a JAK inhibitor on alopecia areata reported to date, based on the magnitude of effect that we see and the time courses of these doses. Especially with the 12-mg twice daily dosing... With this, given the players in the space, I think it sets a new bar for clinical efficacy in treating alopecia areata.”

Update on baricitinib JAK inhibitor trials

This news follows an announcement from pharmaceutical company, Eli Lilly and Company, which recently advised it has 'reached a milestone' in its testing of drug LY3009104, also known as the JAK inhibitor baricitinib, for the treatment of mild to severe forms of Alopecia Areata.

Exploratory trials into using baricitinib to treat patchy hair loss to total baldness caused by the various types of Alopecia Areata, have been underway since at least 2015. They are now entering Phase 3 testing for the treatment of both adults and children.

One aspect it is likely the Lilly team is working on, is reducing the current adverse events profile of baricitinib (brand name: Olumiant), as it carries some pretty serious potential side effect warnings at present in its use as a rheumatoid arthritis medication.

The patient information leaflet and Olumiant website both state the drug 'may cause serious side effects.' These range from 'serious infections, including tuberculosis (TB)' and potentially life-threatening 'blood clots', to 'cancer and immune system problems'.

'Olumiant may increase your risk of lymphoma and other cancers, including skin cancers,' states the manufacturer's warning.

Similar serious side effect profile concerns were raised with regard to the JAK inhibitor tofacitnib (brand name: Xeljanz) when that was first discovered to have beneficial hair regrowth effects for people with autoimmune alopecia.

As part of its development, researchers have been exploring topical options of the drug in order to help reduce side effects found in the systemic version.

Interestingly, Incycte, another pharmaceutical company with whom Lilly is currently partnering to investigate baricitinib as an atopic dermatitis treatment, has previously carried out clinical trials into oral baricitinib.

These are the latest updates from the race to develop the first FDA-approved Alopecia Areata, Totalis and Universalis treatments and we will add more information to the Belgravia blog as addtional news is released.

In the meantime, if you are concerned about sudden hair fall, if you are an adult with hair loss from the scalp only, a consultation with hair loss specialist can provide you with a professional diagnosis and personalised treatment recommendations. If you are an adult losing hair from your scalp and/or other parts of your body, including your face, or if you are under 16 years of age, we recommend speaking to your doctor who may then refer you on to a dermatologist.