The first domestic self-developed oral JAK1 inhibitor - Ruishi Biologics Emmacitinib Tablets, a subsidiary of Hengrui Pharmaceutical, for the treatment of atopic dermatitis has completed the international multi-center phase III clinical trial!

On November 15, Hengrui Pharmaceutical's WeChat public account announced that its subsidiary Ruishi Biopharmaceutical Co., Ltd. (hereinafter referred to as "Ruishi Biopharmacy") has a new generation of highly selective JAK1 inhibitor emaxitinib tablets (Ivarmacitinib tablet) QUARTZ3 (NCT04875169), a phase III international multicenter clinical study for the treatment of atopic dermatitis in adults and adolescents 12 years of age and older, was assessed to meet the study's preset common primary endpoint and all key secondary endpoints.

QUARTZ3 (NCT04875169) is a randomized, double-blind, placebo-controlled, international multicenter phase III registrational clinical study conducted at 15 sites in Canada and 36 sites in China to evaluate the efficacy and safety of emmaxitinib monotherapy in the treatment of moderate to severe atopic dermatitis (AD). A total of 336 participants aged 12 years and older with moderate to severe atopic dermatitis were randomized to receive 8 mg or 4 mg orally once daily imaxitinib tablets or placebo, and participants who completed 16 weeks of treatment were given a 36-week extended treatment period. The study set the internationally recognized common primary endpoints, namely the proportion of participants with an overall investigator score (IGA) of 0 (complete clearance of lesions) or 1 (almost complete clearance of lesions) at week 16 and a ≥2-point decrease from baseline (IGA response), and the proportion of participants with at least a 75% improvement in eczema area and severity index (EASI) from baseline (EASI-75 response) at week 16. In addition, QUARTZ3 set several secondary endpoints, including the proportion of participants with the most severe pruritus index improvement of 4 points or more, EASI-50/90 response rate, and improvement in patient-reported outcomes (POEM and DLQI/CDLQI) from baseline.

Among the participants included in the study, the mean duration of the disease was more than 10 years, and about 40% had previously received systemic treatment. The results of this study showed that once-daily oral emmaxitinib tablets significantly and rapidly improved skin lesion symptoms in patients with atopic dermatitis, and the proportion of participants in the two dose groups of 8 mg and 4 mg at 16 weeks of treatment was significantly higher than that of placebo control (P value < 0.001), respectively. In terms of improving skin itching, imaxitinib can take effect as soon as two days after administration, and from 1 week to 16 weeks of treatment, the proportion of subjects with a numerical score improvement of ≥4 points for the most severe itching in the 8 mg and 4 mg groups of emmasetinib was significantly higher than that in the placebo group (P value < 0.001). This study also included a proportion of adolescents aged 12 years and older, and the results showed that the trend of efficacy of emmaxitinib 8 mg or 4 mg in adolescents was consistent with the general population. No new safety signals were identified during the trial, and the incidence of adverse events in the emmaxitinib group was comparable to that in the placebo group. Ruishi Biotech is conducting further detailed analysis of the research data, and will publish the specific results in academic conferences and professional journals early next year.

Emmaxitinib tablets is the first domestic self-developed new generation JAK1 inhibitor, a national class 1 new drug, and the first domestic self-developed JAK1 inhibitor that has obtained key phase III research success in the field of autoimmune disease treatment. In January 2021, based on its excellent phase II results in people with atopic dermatitis, emmaxitinib tablets were included in the Breakthrough Therapy (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration. Ruishi Biotech is preparing to communicate with the national drug administration on the new drug application and is expected to be the first domestic self-developed JAK1 inhibitor approved for self-exemption indications.

Professor Zhang Jianzhong, principal investigator of the study and director of the Department of Dermatology, Peking University People's Hospital, pointed out:

We are honored to lead the phase II and phase III clinical studies of emmaxitinib tablets in patients with atopic dermatitis, from the enrollment of the first patient in phase II in 2019 to the completion of the phase III study in 2022, which lasted more than 3 years, especially the phase III study, when the impact of the new crown epidemic is greatest, it is very difficult to organize and implement such a high-level international multi-center clinical trial. Now, the phase III top-line results of emmaxitinib tablets in the indication of atopic dermatitis, the common primary endpoint IGA and EASI-75 response rates have met expectations, and the effectiveness of emmaxitinib tablets has been confirmed. During the trial, the overall adverse events of the 4mg group and 8mg group of emmaxitinib tablets were comparable to those in the placebo group, showing the good safety and tolerability of this product in the AD population. As researchers, we are very pleased and would like to express our sincere gratitude to the subjects and all researchers who participated in this project, and with the joint efforts of everyone, this new generation of highly selective JAK1 inhibitor clinical research can be successfully completed in China. It is expected that emmaxitinib tablets will be approved for marketing in China as soon as possible to benefit the majority of patients with atopic dermatitis. ”

Dr. Min Wang, Co-Founder and CEO of Ruishi Biologics, said:

Emmaxitinib tablets are the first blockbuster product of Ruishi Biotech in the past five years since its establishment, and have achieved excellent results in the phase III global clinical study of atopic dermatitis, which not only reached the expected endpoint, but also further demonstrated the experience of Ruishi Bio in practicing high-quality global clinical trials. In addition to adult AD patients, this study also included some adolescents aged 12 years and above, and the relevant research data laid the foundation for the rational drug use of Chinese adolescents in the future. Ruishi Biotech has always been based in China and looking at the world, and is committed to bringing affordable original and innovative drugs to patients with autoimmune diseases in China and around the world. The success of the first pivotal Phase III clinical study will strongly promote the company's commercialization! ”

About emmaxitinib tablets

The research drug emmaxitinib tablets is a national class 1 new drug, which is a highly selective oral JAK1 inhibitor, which belongs to the second generation of JAK inhibitors, and is a domestic independent research and development of oral small molecule innovative drugs with a class of intellectual property rights, which is the first of its kind in China. In addition to atopic dermatitis, emmaxitinib tablets have also carried out phase II/III clinical studies in a number of autoimmune diseases, including ulcerative colitis, Crohn's disease, alopecia areata, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, etc.

About atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin disease with complex lesions and diverse clinical manifestations and symptoms, typically manifested as skin pigmentation, dryness, cracked or scaly plaques, and itchy skin—especially at night—which seriously affects the patient's quality of life. These patients face a long course of disease and a lack of long-term effective clinical therapies to control the disease. In most countries worldwide, the prevalence of atopic dermatitis ranges from 10 to 20 percent in children and 8 to 10 percent in adults [1]; Atopic dermatitis has become a global health problem with a similar burden to chronic diseases such as diabetes and epilepsy [2, 3]. At present, the international community is actively researching new products aimed at regulating the immune response, and the need to develop safer and more effective therapeutic drugs suitable for oral administration is very urgent.

About Ruishi Biopharma

Ruishi Biotech is a new drug discovery company focusing on autoimmune and inflammatory diseases, with advantages in clinical development and global operations. Founded in January 2018, the company is headquartered in Zhangjiang, Shanghai, with offices in Beijing, Wuhan and Chicago. The company brings together the world's top clinical and drug discovery talents and prides itself on industry-leading clinical trial efficiency. The company's drugs under development are all national Class 1 new drugs, and there are currently as many as ten clinical trials in progress; A number of self-developed molecules have entered the preclinical research stage. With the rich and solid experience of multinational pharmaceutical companies in the management team members, Rockstone Biotech's vision is to become a world-renowned biopharmaceutical company by bringing innovative immuno-inflammatory drugs to patients around the world.