L09: Efficacy and Safety of LNK01001 in Chinese Patients with Moderate to Severe Active Rheumatoid Arthritis with an Inadequate Response to Conventional Synthetic DMARDs: 24-week Results from a Phase 2 Trial

Chanyuan Wu¹, Xuebin Wang², Jiankang Hu³, Xiaofei Shi⁴, Xiaoxia Wang⁵, Xuan Zhang⁶, Ju Liu⁷, Hui Rao⁸, Jianhong Zhao⁹, Rong Du¹⁰, Zhenyu Jiang¹¹, Huaxiang liu¹², Lin Liu¹³, Shengyun Liu¹⁴, Changhao Xie¹⁵, Xiangping Liao¹⁶, Lie Dai¹⁷, Zhiduo Hou¹⁸, Jingchun Jin¹⁹, Tianwang Li²⁰, Deqian Meng²¹, Yongfu Wang²², Jian Wu²³, Jieruo Gu²⁴, Wei Wei²⁵, Yu Zhuang²⁶, Kuanting Wang²⁷, Rong Zhang²⁸, Xiao Zhang²⁹, Huaping Wei³⁰, Zhao-Kui Wan³¹, Jun Wang³¹, Michael Vazquez³², Henry Wu³³ and Xiaofeng Zeng¹, ¹Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China, ²Binzhou Medical University Hospital, Binzhou, China, ³Pingxiang People's Hospital, Pingxiang, China, ⁴The 1st Affiliated Hospital of He'nan University, Luoyang, China, ⁵Second Hospital of Shanxi Medical University, Taiyuan, China, ⁶Beijing Hospital, Beijing, China, ⁷Jiujiang No. 1 People's Hospital, Jiujiang, China, ⁸Hunan Provincial People's Hospital, Changsha, China, ⁹Jining First People's Hospital, Jining, China, ¹⁰Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ¹¹First Affiliated Hospital of Jilin University, Changchun, China, ¹²Qilu Hospital of Shandong University, Jinan, China, ¹³Central Hospital of Xuzhou City, Xuzhou, China, ¹⁴The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, ¹⁵The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, ¹⁶Chenzhou First People's Hospital, Binzhou, China, ¹⁷Sun Yat-Sen Memorial Hospital, Guangzhou, China, ¹⁸Shantou University Medical College No.1 Affiliated Hospital, Shantou, China, ¹⁹Yanbian University Affiliated Hospital, Yanbian, China, ²⁰guangdong second provincial general hospital, Guangzhou, China, ²¹Huai'an First People's Hospital, Huaian, China, ²²The First Affiliated Hospital of Baotou Medical College, Baotou, China, ²³The First Affiliated Hospital of Soochow University, Suzhou, China, ²⁴The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, ²⁵Tianjin Medical University General Hospital, Tianjin, China, ²⁶Huizhou Central People's Hospital, Huizhou, China, ²⁷Peking University Shougang Hospital, Beijing, China, ²⁸The First Hospital of China Medial University, Shenyang, China, ²⁹Guangdong Provincial People's Hospital, Guangzhou, China, ³⁰Lynk Pharmaceuticals Co., Ltd., Hangzhou, China, ³¹Lynk Pharma, Hangzhou, China, ³²Lynk Pharma, Saint Louis, MO, ³³Lynk Pharma, Nanjing, China

Background/Purpose: LNK01001 is a selective oral JAK1 inhibitor in clinical development for treating autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). Here, we report the 24-week efficacy and safety results of LNK01001 in patients with moderate to severe active RA who had an inadequate response to csDMARDs.

Methods: Eligible participants aged 18 to 75 with a diagnosis of moderate to severe active RA who met ACR/EULAR 2010 criteria and had an inadequate response to csDMARDs, were randomized (1: 1: 1) to receive LNK01001 12mg or 24mg twice daily (BID), or placebo for 12 weeks, followed by a 12-week extension treatment with LNK01001 12mg or 24mg. The primary endpoint was the proportion of patients achieving an ACR20 response at Week 12.

Results: All 156 patients randomized were included in the analysis. The mean age was 52.4 years, and 76.9% were female, mean DAS28-CRP score was 5.884. Baseline characteristics were similar across treatment groups. At week 12, a significantly higher proportion of patients achieved ACR20, ACR50 and ACR70 in LNK01001 12 mg and 24 mg groups compared with the placebo group (ACR20: 60.0% [95%CI: 45.2, 73.6], 73.1% [95%CI: 59.0, 84.4], vs 31.5% [95%CI: 19.5, 45.6], both doses p< 0.01; ACR50: 40.0% [95%CI: 26.4, 54.8], 42.3% [95%CI: 28.7, 56.8], vs 9.3% [95%CI: 3.1, 20.3], both doses p< 0.001; and ACR70: 12.0% [95%CI: 4.5, 24.3], 23.1% [95%CI: 12.5, 36.8], vs 1.9% [95%CI: 0.0, 9.9], both doses p < 0.05). A statistically significant difference was reached as early as Week 1 in ACR20 for both doses of LNK01001 vs placebo (18.0% [95%CI: 8.6, 31.4], 23.1% [95%CI: 12.5, 36.8], vs 0% [95%CI: 0, 6.6], both doses p＜0.01). Disease activity reduction measured by DAS28-CRP and functional ability improvement of HAQ-DI were significant in patients treated with LNK01001 compared to patients treated with placebo (-2.518, -2.614, vs -1.263, both doses p＜0.0001; and -0.64, -0.73, vs -0.34, both doses P < 0.01). During extension treatment, the proportion of patients achieving ACR20/50/70, DAS28 (≤ 3.2 and < 2.6), SDAI (≤ 11 and ≤ 3.3) and CDAI (≤ 10 and ≤ 2.8) response increased steadily over time. At week 24, 91.1% (95%CI: 78.8, 97.5) and 90.7% (95%CI: 77.9, 97.4) of patients achieved ACR20 in LNK01001 12mg and 24mg group, respectively.

The most frequently reported TEAE in patients receiving LNK01001 was hyperlipidemia. No serious infection, malignancy, venous thromboembolism or major adverse cardiovascular events were reported up to 24 weeks.

Conclusion: Treatment with LNK01001 12 mg or 24 mg BID up to 24 weeks in patients with moderate to severe active RA and an inadequate response to csDMARDs were generally safe, and well tolerated with most TEAEs being mild to moderate. Both doses were superior to placebo in reducing the severity of rheumatoid arthritis over a period of 12 weeks across multiple efficacy end points.


Efficacy and Safety of LNK01001 in Chinese Patients with Moderate to Severe Active Rheumatoid Arthritis with an Inadequate Response to Conventional Synthetic DMARDs: 24-week Results from a Phase 2 Trial

C. Wu: None; X. Wang: None; J. Hu: None; X. Shi: None; X. Wang: None; X. Zhang: None; J. Liu: None; H. Rao: None; J. Zhao: None; R. Du: None; Z. Jiang: None; H. liu: None; L. Liu: None; S. Liu: None; C. Xie: None; X. Liao: None; L. Dai: None; Z. Hou: None; J. Jin: None; T. Li: None; D. Meng: None; Y. Wang: None; J. Wu: None; J. Gu: None; W. Wei: None; Y. Zhuang: None; K. Wang: None; R. Zhang: None; X. Zhang: None; H. Wei: None; Z. Wan: Lynk Pharmaceuticals, 3, 4, 8, 10; J. Wang: None; M. Vazquez: None; H. Wu: None; X. Zeng: None.