Hangzhou, China (April 27, 2026) Highlightll Pharmaceutical today announced that the Phase Ⅲ clinical trial of its oral small molecule JAK1/TYK2 inhibitor girocitinib for the treatment of rheumatoid arthritis (“RA”) had achieved positive topline results, significantly outperforming the positive comparator tofacitinib in the primary and all secondary efficacy endpoints, and demonstrated good safety and tolerability.
The first registrational trial with a positive control in RA and achieved superiority
This study is a multicenter, randomized, double-blind phase Ⅲ clinical trial to evaluate the efficacy and safety of girocitinib in patients with rheumatoid arthritis who had inadequate response or were intolerant to biologics. A total of 459 subjects were randomized to receive girocitinib or tofacitinib for 52 weeks. The primary efficacy endpoint is the ACR50 rate at week 24, which is also the first phase Ⅲ study in the world to use ACR50 as the primary endpoint.
Girocitinib demonstrated superior efficacy over tofacitinib in this trial. Girocitinib also showed significantly better efficacy than tofacitinib on key secondary endpoints (P<0.0001), including the ACR20/70 rates, the proportion of subjects with DAS28≤3.2 and DAS28<2.6, and the proportion of subjects with low disease activity (LDA) who achieved CDAI≤10. In addition, patients who did not reach ACR50 in the tofacitinib group achieved better efficacy after being transferred to the girocitinib group, indicating that girocitinib may still be effective in patients with poor response to both biologics and JAK inhibitors (difficult-to-treat patients). At present, there is no drug approved for the difficult-to-treat patients, an unmet medical need.
Professor Zeng Xiaofeng, the lead principal investigator of this study at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, commented: "Rheumatoid arthritis is an important cause of disability in the Chinese population and brings a heavy economic burden to families and society. This trial is being conducted by more than 60 centers in China and is the world's first registrational Phase 3 trial using head-to-head comparison with another JAKi in RA. The trial met the primary endpoint and all secondary endpoints.
Although there are multiple drugs with different mechanisms of action on the market, many patients have not yet achieved the treatment goal of clinical remission or low disease activity. The ACR50/70 rate and the proportion of subjects in clinical remission or low disease activity were significantly higher in the girocitinib group than the tofacitinib group, suggesting that girocitinib has the potential to help more RA patients achieving remission, which is promising.”
Girocitinib demonstrated a good safety profile with no new safety signal
The incidences of adverse events, severe adverse events and serious adverse events between the two groups were very similar, and the adverse event profile is consistent with other JAK inhibitors with no new safety signal. The follow-up of the current study is still ongoing, and the complete data will be published in future academic conferences or peer-reviewed academic journals.
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.
