SHANGHAI, China, Dec. 29, 2022 (GLOBE NEWSWIRE) -- Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences”, HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, today announces the online publication in New England Journal (NEJM) of the Phase 3 trial (NCT05341609) comparing the efficacy and safety of VV116 (JT001) and nirmatrelvir/ritonavir (“PAXLOVID”) in the treatment of symptomatic patients with mild to moderate COVID-19 who are at high risk for progression to severe COVID-19 including death. It is the first time that NEJM published the clinical trial results of China-developed anti-SARS-CoV-2 drug. The study, led by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, is the first “head-to-head” phase III clinical study of small molecule oral anti-SARS-CoV drug in Chinese COVID-19 patients during the Omicron outbreak. The results indicated that the primary endpoint of the study realized the designed noninferiority endpoint, and VV116 group had a shorter time to sustained clinical recovery with less safety concerns as compared with PAXLOVID. The Article was co-authored by Professor Ren ZHAO of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Professor Yuan GAO of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Professor Guang NING, Professor Yiping XU and Professor Qing XIE of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine as co-corresponding authors, Zhujun CAO and Weiyi GAO of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Hong BAO of Pudong Hospital, Fudan University, Haiyan FENG of Shanghai Public Health Clinical Center and Shuya MEI of Renji Hospital, Shanghai Jiao Tong University School of Medicine as co-first authors. "Thanks to the support of the patients and study team, we have achieved great success in this clinical study and were recognized by the prestigious New England Journal of Medicine,” said Professor Ren ZHAO. “Our study not only provided valuable information and experience for the development and clinical application of two major anti-SARS-CoV-2 small molecule drug routes, the RdRp inhibitor and the 3CL protease inhibitor, but also showed that our self-developed anti-SARS-CoV-2 oral drugs in China have similar efficacy and safety to PAXLOVID. We hope that our study results can assist in our nation’s efforts to combat the epidemic.” "Presently, the treatment and prevention of COVID-19 is still full of challenges, particularly in the treatment of patients who are at high risk for progression to severe COVID-19," said Jianjun ZOU, Global Research and Development President at Junshi Biosciences. "The current treatment needs to be made more widely applicable and accessible to a larger population. The publication of this study in the NEJM demonstrates that the international academic community has recognized the clinical development of drugs led by Chinese investigators and pharmaceutical companies in terms of trial design, quality, and results. We are continuing to invest in the clinical development of VV116 for use in other populations, with the goal of providing better and safer treatment options for COVID-19 patients in China and around the world with this exciting new therapy!" At present, the COVID-19 pandemic continues to spread rapidly worldwide, and the transmission and escape ability of the virus continues to increase with variation. Oral antiviral drugs are considered to be one of the essential response against the pandemic because of their advantages of convenient administration, high resistance barrier, and less transportation and storage restrictions, which help to alleviate the medical burden. However, there are still a number of factors that lead to limited use of the drugs (such as the interaction between drug and drug, accessibility, etc.), so more effective and safe therapeutic drugs need to be developed. VV116 is an oral nucleoside antiviral drug independently developed in China that inhibits the replication of SARS-CoV-2. Preclinical studies have shown that VV116 had significant antiviral effects in both original strain and known mutant strains, and exhibited satisfactory safety, tolerability, and pharmacokinetic properties in phase I clinical studies1. A preliminary small-scale study confirmed that patients, who were treated with VV116 within 5 days since they were tested positive after the first SARS-CoV-2 detection, had a shorter time to nucleic acid reversion compared to conventional therapy2. This publication is related to a multicenter, single-blind (observers remain blinded), randomized, controlled Phase III clinical trial (NCT05341609) conducted jointly at seven COVID-19 designated hospitals in Shanghai from April 4 to May 2, 20223, which included a total of 822 adult patients with mild to moderate COVID-19 diagnosed at high risk of progression and assigned to the VV116 group and PAXLOVID group on a proportion of 1:1. Finally, a total of 771 patients (Full Analysis Set, FAS) were treated with VV116 (n = 384) or PAXLOVID (n = 387). Among them, the median age of FAS patients was 53 (range: 18-94), 50.2% of them were female, 92.1% of them had mild COVID-19, 75.7% of them were fully vaccinated or boosted, and 77.3% of them received VV116 or PAXLOVID therapy within 5 days after symptom onset. The most common high-risk factors in patients were: age ≥ 60 years (37.7%), cardiovascular disease including hypertension (35.1%), obesity or overweight BMI ≥ 25 (32.9%), current smoking (12.5%), and diabetes (10.1%). The primary end point of the study was the time from randomization to sustained clinical recovery, with a lower boundary of the two-sided 95% confidence interval (CI) for the hazard ratio (HR) > 0.8 defined as noninferiority. Secondary efficacy end points included the proportion of patients who progressed to severe or critical COVID-19 or death from any cause by Day 28, the change in COVID-19 related symptom score and the score on the WHO Clinical Progression Scale, time to sustained resolution of all target symptoms, and to a first negative SARS-CoV-2 test. Safety endpoints included adverse events (AEs) and serious adverse events (SAEs). According to the final analysis (as of August 18, 2022), VV116 and PAXLOVID achieved noninferiority in the “time to sustained clinical recovery” in the FAS population (HR = 1.17, 95% CI: 1.02~1.36), and the median time to sustained clinical recovery was shorter in the VV116 group than that in the PAXLOVID group (4 days vs. 5 days). For VV116 group and PAXLOVID group, they showed similar results in respect of “time to sustained resolution of all target symptoms” and “time to a first negative SARS-CoV-2 test”, with a median time of 7 days. At each preset time point (Days 5, 7, 10, 14, and 28), the proportion of patients with clinical recovery was larger in the VV116 group than that in the PAXLOVID group. No patients in either group hase progression to severe/critical COVID-19 or had died. In addition, about 3/4 of the patients in this study had vaccinated against SARS-CoV-2, and such patients have been excluded from most trials, and subgroup analysis showed that there was no statistically significant difference in the treatment results between VV116 and PAXLOVID in the vaccinated or unvaccinated population. VV116 showed fewer safety concern than PAXLOVID. The incidence of AEs in VV116 group was lower than that in the PAXLOVID group (all-grade AEs: 67.4% vs. 77.3%, Grade 3 or 4 AE: 2.6% vs. 5.7%). It should be noted that PAXLOVID has multiple drug-drug interactions, while VV116 does not inhibit or induce major drug-metabolism enzymes, or inhibit major drug transporters, and is therefore less likely to interact with the drugs for combination therapy. About VV116 (JT001)VV116 is an oral nucleoside analog drug that can inhibit the replication of SARS-CoV-2. During preclinical pharmacodynamic studies, VV116 exerted an antiviral effect on the original strain of the novel coronavirus and its known variants in vitro; in the mice model, a low dose of VV116 reduced the virus titers below the detection limit, significantly lowered the chances of lung injury and displayed a strong antiviral effect. Preclinical pharmacokinetics and other research results also show that VV116 has high oral bioavailability. Following oral administration and absorption, VV116 is rapidly metabolized into parent nucleoside and widely distributed throughout the body. VV116 was jointly developed by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences; the Wuhan Institute of Virology, Chinese Academy of Sciences; Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences; Central Asian Center of Drug Discovery and Development Chinese Academy of Sciences / China-Uzbekistan Medicine Technical Park (the Joint Laboratory of the Ministry of Science and Technology under the "The Belt and Road Initiative"); Lingang Laboratory; Vigonvita Life Sciences Co., Ltd. (“Vigonvita”); and Junshi Biosciences. Junshi Biosciences and Vigonvita are responsible for the clinical development and industrialization of VV116 worldwide. The areas of cooperation is global aside from five Central Asian countries, Russia, North Africa and the Middle East. Junshi Biosciences and Vigonvita have completed three Phase I studies with healthy Chinese subjects, and one Phase III study in the patients with mild-to moderate COVID-19 at high risk to progression to severe COVID-19 in China (NCT05341609). Research results have been published in Acta Pharmacologica Sinica, and NEJM respectively. In 2021, VV116 was approved in Uzbekistan for the treatment of patients diagnosed with moderate to severe COVID-19. About Junshi BiosciencesFounded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of innovative therapeutics. The company has established a diversified R&D pipeline comprising over 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for anti-PD-1 monoclonal antibody in China. Its first-in-human anti-BTLA monoclonal antibody for the treatment of various cancers was the first in the world to be approved for clinical trials by the FDA and NMPA and has since entered Phase Ib/II trials in both China and the US. Its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA. In the face of the pandemic, Junshi Biosciences’ response was strong and immediate, joining forces with Chinese and international scientific research institutions and enterprises to develop an arsenal of drug candidates to combat COVID-19, taking the initiative to shoulder the social responsibility of Chinese pharmaceutical companies by prioritizing and accelerating COVID-19 R&D. Among the many drug candidates is JS016 (etesevimab), China’s first neutralizing fully human monoclonal antibody against SARS-CoV-2 and the result of the combined efforts of Junshi Biosciences, the Institute of Microbiology of the Chinese Academy of Science and Lilly. JS016 administered with bamlanivimab has been granted Emergency Use Authorizations (EUA) in over 15 countries and regions worldwide. As of December 3 2021, over 700,000 patients have been treated with bamlanivimab or bamlanivimab and etesevimab, potentially preventing more than 35,000 hospitalizations and at least 14,000 deaths. Meanwhile, VV116, a new oral nucleoside analog anti-SARS-CoV-2 drug designed to hinder virus replication, is in global Phase III clinical trials. The JS016 and VV116 programs are a part of the company’s continuous innovation for disease control and prevention of the global pandemic. Junshi Biosciences has more than 3,100 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc). For more information, please visit: http://junshipharma.com. Junshi Biosciences Contact InformationIR Team:Junshi Biosciencesinfo@junshipharma.com+ 86 021-6105 8800 PR Team:Junshi BiosciencesZhi Lizhi_li@junshipharma.com+ 86 021-6105 8800 ____________________________ 1 Qian, Hj., et al. Acta Pharmacol Sin (2022).2 Shen Y, et al. Emerg Microbes Infect 2022;11:1518-23.3 The seven hospitals participating in the study were: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Renji Hospital, Shanghai Jiao Tong University School of Medicine; Pudong Hospital, Fudan University; Shanghai Public Health Clinical Centre; Shuguang Hospital, Shanghai University of Traditional Chinese Medicine; Huashan Hospital, Fudan University; and Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine.
