Reistone's Ivarmacitinib, China's First Homegrown Oral JAK1 Inhibitor, Meets Primary Endpoints in Global Phase III Trial for Atopic Dermatitis
Shanghai, China, November 15, 2022:Reistone Biopharma (Reistone), a leading biopharmaceutical company focused on the research and development of innovative immunology and inflammation therapies and precision medicine drugs:Recently announced that the Company’s Phase III international, multicenter clinical study of its next-generation highly selective JAK1 inhibitor, ivarmacitinib tablets, for the treatment of atopic dermatitis in adults and adolescents aged 12 years and older, QUARTZ3 (NCT04875169), met the prespecified co-primary endpoints and all key secondary endpoints. In May 2022, the Company secured nearly USD 100 million in Series A financing, led by Huagai Capital Medical Fund.
QUARTZ3（NCT04875169）This is a randomized, double-blind, placebo-controlled, international, multicenter, Phase III registrational clinical study conducted at 15 research centers in Canada and 36 research centers in China. The study aims to evaluate the efficacy and safety of emraclitinib tablets as monotherapy in patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks. A total of 336 subjects aged 12 years and older with moderate-to-severe atopic dermatitis were enrolled and randomly assigned to receive once-daily oral emraclitinib tablets at doses of 8 mg or 4 mg, or placebo. Subjects who completed the 16-week treatment period entered a 36-week extension treatment phase. The study employed internationally recognized co-primary endpoints: the proportion of subjects achieving an Investigator’s Global Assessment (IGA) score of 0 (clear skin) or 1 (almost clear), with a reduction of ≥2 points from baseline (IGA response), and the proportion of subjects achieving at least a 75% improvement in the Eczema Area and Severity Index (EASI) from baseline (EASI-75 response) at Week 16. Additionally, QUARTZ3 included multiple secondary endpoints, such as the proportion of subjects achieving an improvement of ≥4 points in the Worst Pruritus Numeric Rating Scale (NRS), EASI-50/90 response rates, and improvements from baseline in patient-reported outcomes (POEM and DLQI/CDLQI).
Among the subjects enrolled in the study, the mean disease duration exceeded 10 years, and approximately 40% had previously received systemic therapy. The results of this study demonstrated that once-daily oral administration of SHR0302 tablets significantly and rapidly improved skin lesions in patients with atopic dermatitis. At Week 16, the proportions of patients achieving the co-primary efficacy endpoints of Investigator’s Global Assessment (IGA) response and EASI-75 response in both the 8 mg and 4 mg dose groups were significantly higher than those in the placebo group (both P < 0.001). Regarding the improvement of pruritus, SHR0302 showed onset of action as early as two days after initiation. From Week 1 to Week 16, the proportions of patients achieving an improvement of ≥4 points in the Worst Pruritus Numerical Rating Scale (NRS) score were significantly higher in the SHR0302 8 mg and 4 mg groups than in the placebo group (both P < 0.001). This study also included a certain proportion of adolescent patients aged 12 years and older. The results indicated that the efficacy trends of SHR0302 8 mg or 4 mg in adolescents were consistent with those observed in the overall population. No new safety signals were identified during the trial, and the incidence of adverse events in the SHR0302 groups was comparable to that in the placebo group. Henlius is conducting further detailed analyses of the study data, and specific results will be presented at academic conferences and published in professional journals early next year.
Ivarmacitinib Tablets is the first next-generation JAK1 inhibitor independently developed in China, classified as a National Class 1 New Drug. It is also the first domestically developed JAK1 inhibitor to achieve success in pivotal Phase III clinical trials for the treatment of autoimmune diseases.In January 2021, based on its excellent Phase II results in the atopic dermatitis population, Ivarmacitinib tablets were included in the Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration. RUISTONE Biopharma is preparing to communicate with national drug regulatory authorities regarding the New Drug Application (NDA), and it is expected to become the first domestically developed JAK1 inhibitor approved for autoimmune indications.
Professor Zhang Jianzhong, Chief of the Department of Dermatology at Peking University People's Hospital and Principal Investigator of this studyThe investigator stated, “We were honored to lead the Phase II and Phase III clinical studies of ivarmacitinib tablets in patients with atopic dermatitis (AD). The process spanned over three years, from the enrollment of the first patient in the Phase II trial in 2019 to the completion of the Phase III study in 2022. Organizing and implementing such a high-level international multicenter clinical trial was particularly challenging during the peak impact of the COVID-19 pandemic, especially for the Phase III study. Currently, the top-line results from the Phase III trial for the AD indication have met expectations, with both co-primary endpoints—the Investigator’s Global Assessment (IGA) response rate and the EASI-75 response rate—achieving the anticipated outcomes, thereby confirming the efficacy of ivarmacitinib tablets. During the trial, the overall incidence of adverse events in the 4 mg and 8 mg ivarmacitinib groups was comparable to that in the placebo group, demonstrating the favorable safety and tolerability profile of this product in the AD population. As investigators, we are deeply gratified and wish to express our sincere gratitude to all participants and researchers involved in this project. Thanks to our collective efforts, the clinical development of this first-in-class, next-generation highly selective JAK1 inhibitor in China has been successfully completed. We look forward to the imminent approval and market launch of ivarmacitinib tablets in China, bringing benefit to a broad population of patients with atopic dermatitis.”
Dr. Min Wang, Co-founder and CEO of RStone BiotherapeuticsStatement: “Ivarmacitinib tablets represent the first blockbuster product launched by RemeGen in its nearly five years of operation, achieving outstanding results in the global Phase III clinical trials for atopic dermatitis. The study not only met its primary endpoints but also further demonstrated RemeGen’s consistent commitment to conducting high-quality global clinical trials. In addition to adult patients with atopic dermatitis (AD), the study enrolled a subset of adolescent patients aged 12 years and older, providing data that lay the foundation for rational medication use among Chinese adolescents in the future. Rooted in China with a global perspective, RemeGen is dedicated to delivering affordable, original innovative medicines to patients with autoimmune diseases both in China and worldwide. This inaugural success in a pivotal Phase III clinical study will significantly propel the company toward commercialization.”
Ivarmacitinib tablets, the investigational drug, is a National Class I new drug. It is an oral, highly selective JAK1 inhibitor belonging to the second generation of JAK inhibitors. As an orally administered small-molecule innovative drug with independent intellectual property rights developed in China, it represents the first product of its kind domestically. In addition to atopic dermatitis, Ivarmacitinib tablets are undergoing Phase II/III clinical trials for multiple autoimmune diseases, including ulcerative colitis, Crohn's disease, alopecia areata, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis.
Atopic dermatitis is a chronic inflammatory skin disease characterized by complex pathological changes and diverse clinical manifestations and symptoms. Typical presentations include skin hyperpigmentation, dryness, fissures or scaly plaques, and pruritus—particularly nocturnal itching—which severely impairs patients' quality of life. Patients endure the torment of a prolonged disease course, compounded by the current lack of clinically available therapies for long-term and effective disease control. In most countries worldwide, the prevalence of atopic dermatitis reaches 10%–20% in children and 8%–10% in adults [1]. Atopic dermatitis has become a global health issue with a disease burden comparable to that of chronic conditions such as diabetes and epilepsy [2,3]. Currently, there is active international research into novel agents that modulate immune responses, and there is an urgent need to develop oral therapeutic drugs with improved safety and efficacy.
Rui Shi Biologics is a novel drug R&D company focused on the field of autoimmune and inflammatory diseases, with strengths in clinical development and global operations. Founded in January 2018, the company is headquartered in Zhangjiang, Shanghai, with offices in Beijing, Wuhan, and Chicago, USA. The company has gathered top-tier global talent in clinical development and drug discovery, and takes pride in its industry-leading clinical trial efficiency. All drugs under development are Class 1 new drugs approved by the National Medical Products Administration (NMPA), with up to ten clinical trials currently ongoing; multiple self-developed molecules have entered the preclinical research stage. Leveraging the extensive and solid experience of its management team from multinational pharmaceutical companies, Rui Shi Biologics aims to become a globally renowned biopharmaceutical company by bringing innovative immunoinflammatory drugs to patients worldwide.
References
[1] Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1. Published 2018 Jun 21.
[2] Paller A, Jaworski JC, Simpson EL, Boguniewicz M, Russell JJ, Block JK, et al. Major comorbidities of atopic dermatitis: beyond allergic disorders. Am J Clin Dermatol. 2018;19:821–38.
[3] Drucker, A. M. et al. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J. Invest. Dermatol. 2016. 137, 26–30.