Can a new JAK inhibitor help urticaria?

3 minute read

Already making a splash in rheumatology, the drug is now showing potential for persistent hives.

Early research on a TYK2/JAK1 inhibitor called TLL-018 has provided promising results for treatment of moderate-to-severe chronic spontaneous urticaria (CSU).

If the drug doesn’t ring any bells, that’s possibly because it hasn’t ventured far beyond the medical conference circuit. Yet.

Its latest outing was at the American Academy of Allergy Asthma & Immunology annual meeting in February in Washington DC, where Phase1b results appeared in a late-breaking poster.

In the first clinical trial of a JAK inhibitor for CSU, TLL-018 proved successful, with statistically significant differences for UAS7 and ISS7 change from baseline when compared with placebo at week four. There were continued improvements to week 12.

The trial, which was conducted in China, enrolled 41 patients with CSU and an inadequate response to antihistamine. They were allocated to one of three groups: 10mg or 30mg TLL-018, or placebo twice daily.

At the four-week mark, those in the placebo group were switched to 20mg TLL-018 twice daily, and all patients were treated for a further eight weeks.

The main outcome measures were change from baseline in Urticaria Activity Score (UAS7) and Itch Severity Score (ISS7) and percentage achieving UAS7≤6 and UAS7=0.

More than half the patients in all treatment groups achieved UAS7≤6 by week 12. More than half the patients in the 10mg and 30mg groups achieved a zero on the UAS7, and slightly less for the 20mg group – they’d only had eight weeks of treatment. There were no concerning safety signals.

“TLL-018 was well tolerated and showed high efficacy among all dosage groups in moderate-to-severe CSU patients with inadequate response to high doses or a combination of antihistamine treatment in terms of reducing itchiness, hives and improving quality of life,” wrote the authors.

“JAK Inhibitors promise new treatment option for CSU patients,” they concluded.

The drug is also being investigated in a phase 2 trial for psoriasis at multiple centres in the US, following a similar trial in China.

TLL-018 has already caused quite a sensation in the rheumatology space, with data presented at the 2023 European Alliance of Associations for Rheumatology meeting in June demonstrating its marked superiority in a phase 2a head-to-head trial with JAK inhibitor tofacitinib for rheumatoid arthritis.

The final phase 2a data, presented at the American College of Rheumatology (ACR) Convergence in November 2023, confirmed the good news story, arousing audience amazement and scepticism in equal measure.

“Spectacular compound. Absolutely spectacular. Unbelievably spectacular,” remarked Professor Roy Fleischmann, a highly regarded expert in rheumatoid arthritis, after the presentation.

The drug developer, Highlightll Pharma, is forging ahead with a phase 3 trial of 450 patients and is currently recruiting at various locations within China.

Professor Fleischmann asked the presenter, Dr Congxin Liang, why they aren’t doing a multinational phase 3 study, “which would give us more confidence in the results”.

Dr Liang explained that it came down to cost and speed – they wanted to get it registered in China as quickly as possible.

L36 Efficacy and Safety of TLL-018 in Moderate to Severe Chronic Spontaneous Urticaria Patients with Inadequate Response to H1 Antihistamine: Results from a PhaseⅠb Study

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