Highlightll today announced positive topline data from its Phase Ⅲ clinical trial (NCT06396026, “the Study”) evaluating Girocitinib (TLL-018), an oral small-molecule JAK1/TYK2 inhibitor, for the treatment of chronic spontaneous urticaria (CSU).
In the pre-specified interim analysis, Girocitinib met the primary endpoints, demonstrated statistically significant superiority to placebo on the primary efficacy endpoints and multiple secondary efficacy endpoints, and showed a favorable safety and tolerability profile, supporting continuation of the Study per protocol.
Interim Analysis Summary
In this interim analysis, at Week 12, patients treated with Girocitinib achieved significantly greater improvements versus placebo in both UAS7 and ISS7, with differences that were statistically significant and clinically meaningful (p<0.0001). In addition, treatment effects were observed as early as Day 2 and continued to improve on subsequent treatment.
The interim analysis showed that rates of serious adverse events (SAEs) and adverse events requiring intervention were generally comparable between the Girocitinib and placebo groups. No major adverse cardiovascular events (MACE) or drug-related malignancies were observed. For liver safety, ALT/AST elevations were lower in the Girocitinib group than in the placebo group, and no drug-induced liver injury (DILI) was reported. Treatment-related adverse events were primarily mild to moderate laboratory abnormalities and infections, consistent with the known pharmacology of JAK inhibitors.
Principal Investigator Comments
Professor Qianjin Lu, Co-Lead Principal Investigator of the Study at the Hospital (Institute) of Dermatology, Chinese Academy of Medical Sciences, stated:
“The Phase Ⅲ clinical study of Girocitinib for the treatment of chronic spontaneous urticaria has achieved positive results, providing a new potential therapeutic option for patients with this disease. From early dose-exploration studies through the pivotal confirmatory Phase Ⅲ trial, the Study was conducted with the participation of clinical research centers across China, demonstrating China’s independent capabilities in innovative drug development for autoimmune diseases. We also sincerely thank all investigators for their strong support of this Study.
These results reflect the continuous strengthening of China’s capabilities in the development of novel therapies for immune-mediated skin diseases. We look forward to seeing more high-quality, mechanism-driven treatments enter clinical practice in the future, ultimately benefiting patients and advancing the overall standard of dermatologic care.”
Professor Jianzhong Zhang, Co-Lead Principal Investigator of the Study at Peking University People’s Hospital, added: “The Phase Ⅲ results of Girocitinib in chronic spontaneous urticaria (CSU) represent a truly exciting and meaningful milestone. The highlight of this Study is that Girocitinib is the world’s first highly selective dual JAK1/TYK2 inhibitor developed for CSU, enabling more comprehensive and precise blockade of the key driving signals of CSU and delivering strong clinical efficacy. This therapy represents a revolutionary approach to targeted treatment for CSU and is a genuine First-in-Class innovation.
From a clinical perspective, the data are encouraging. Girocitinib demonstrated rapid and durable improvements in pruritus and hives, with an overall favorable safety profile. Originating in China and advanced from discovery through clinical validation by the Highlightll team, this globally innovative program has the potential to become a meaningful new therapy for patients worldwide. We look forward to its potential approval and broader availability, and to contributing to continued progress in the treatment of immune-mediated skin diseases.”
About the Study
The Study is a multicenter, randomized, double-blind, placebo-controlled Phase Ⅲ trial in China designed to evaluate the efficacy and safety of Girocitinib in patients with moderate-to-severe CSU who have had an inadequate response to second-generation H1 antihistamines. A total of 440 patients were enrolled and randomized in a 3:1 ratio to receive Girocitinib or placebo.
About Chronic Spontaneous Urticaria (CSU)
CSU is a chronic inflammatory skin disease characterized by recurrent hives, pruritus, and/or angioedema, with symptoms typically persisting for more than six months. CSU has a high relapse rate, can severely disrupt sleep, and may significantly impair patients’ quality of life and psychological well-being.
The prevalence of CSU is estimated at approximately 1%–2.7%, affecting about 50 million patients worldwide and approximately 10 million patients in China. While second-generation H1 antihistamines are first-line therapy, around 30% of patients remain inadequately controlled, underscoring a substantial unmet medical need.
About Girocitinib (TLL-018)
Girocitinib (TLL-018) is a highly selective, orally administered small-molecule JAK1/TYK2 inhibitor designed to modulate key immune-inflammatory signaling pathways for the treatment of multiple autoimmune and inflammatory diseases. The compound has been evaluated in more than 1,000 subjects across the United States and China to date. Girocitinib is currently being evaluated in Phase Ⅲ clinical trials in China for CSU and rheumatoid arthritis (RA).
About Highlightll
Highlightll is a clinical-stage biopharmaceutical company focused on autoimmune/inflammatory diseases affecting both the peripheral and central nervous systems. The company is dedicated to discovering breakthrough medicines with the potential to make a meaningful impact on patient care. Highlightll leverages global resources and deep expertise, combined with a unique development perspective, to address complex medical challenges.
Highlightll’s lead programs include the world’s first highly selective JAK1/TYK2 dual inhibitor platform. TLL-018 is a peripherally acting JAK1/TYK2 inhibitor currently in Phase Ⅲ clinical trials for CSU and RA. The company’s brain-penetrant JAK1/TYK2 inhibitor, TLL-041, was licensed ex-China to Biohaven in 2023; Biohaven advanced BHV-8000/TLL-041 into global Phase Ⅱ/Ⅲ pivotal trials for Parkinson’s disease in May 2025. NLRP3 is Highlightll’s second platform, with HL-400 being developed for neurodegenerative diseases and HL-450 for peripheral indications.
