High-Risk Adults Reap the Benefits of Junshi Biosciences’ VV116: Phase 3 Study Results Published in NEJM

Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences”, HKEX: 1877; SSE: 688180) is proud to announce that their 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, has been published in the prestigious New England Journal (NEJM). This marks the first time that NEJM has published the clinical trial results of a China-developed anti-SARS-CoV-2 drug and further demonstrates Junshi Biosciences’ dedication to discovering, developing, and commercializing novel therapies.

The groundbreaking phase III clinical study conducted by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, is the first of its kind to compare the efficacy of small molecule oral anti-SARS-CoV drugs in Chinese COVID-19 patients during the Omicron outbreak. The results showed that VV116 demonstrated a faster recovery time with fewer safety concerns, making it the superior choice for treating the virus.

This article was authored by renowned academics from Shanghai Jiao Tong University School of Medicine, including Professor Ren Zhao, Professor Yuan Gao and Professor Guang Ning, as well as co-corresponding authors Professor Yiping Xu, Professor Qing Xie, Zhujun Cao and Weiyi Gao from Ruijin Hospital, and Hong Bao from Pudong Hospital, Fudan University. Haiyan Feng from Shanghai Public Health Clinical Center and Shuya Mei of Renji Hospital, Shanghai Jiao Tong University School of Medicine, also co-authored this article as first authors.

Thanks to the support of the patients and study team, we are proud to have achieved great success in this clinical study – to the point of being recognized by the prestigious New England Journal of Medicine. Our study offers invaluable 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. What’s more, our self-developed anti-SARS-CoV-2 oral drugs in China were found to have similar efficacy and safety to PAXLOVID. We hope that our study results will be of great contribution to our nation’s efforts to combat the epidemic.

The recent publication of a study in the NEJM, demonstrating the clinical development of drugs led by Chinese investigators and pharmaceutical companies, is a major breakthrough in the treatment and prevention of COVID-19. Junshi Biosciences’ Global Research and Development President, Jianjun ZOU, is confident that this new therapy, VV116, will provide a better and safer treatment option for patients around the world. Investment in the clinical development of VV116 continues, as the team strives to make it more widely applicable and accessible to a larger population. In this way, they hope to contribute to our nation’s efforts in combating the epidemic.

At present, the severity of the COVID-19 pandemic is escalating globally, and the virus is becoming increasingly transmissible and mutable. Oral antiviral drugs are a viable solution to the crisis due to their ease of administration, high resistance barrier, and minimal transportation and storage requirements. Nevertheless, many factors, such as drug-drug interactions and accessibility, are preventing the full utilization of these drugs. To combat this, more effective and safe therapeutic drugs need to be developed.

A groundbreaking Chinese developed oral nucleoside antiviral drug, VV116, is showing significant promise in the fight against SARS-CoV-2. Preclinical studies have revealed the drug’s efficacy against both the original strain and known mutants, and the safety, tolerability, and pharmacokinetic properties have been confirmed in a Phase I clinical study. Moreover, a preliminary small-scale study has demonstrated that VV116 treatment within five days of a positive SARS-CoV-2 test result could reduce the time to nucleic acid reversion when compared to conventional therapies.

A groundbreaking Phase III clinical trial (NCT05341609) was conducted at seven COVID-19 designated hospitals in Shanghai, from April 4 to May 2, 20223, with 822 adult patients with mild to moderate COVID-19 at high risk of progression. The trial was single-blind, with observers remaining blinded, and randomized, with patients assigned to the VV116 group and PAXLOVID group on a proportion of 1:1. Out of the 822 patients, 771 (Full Analysis Set, FAS) completed the trial, receiving VV116 (n = 384) or PAXLOVID (n = 387). This ambitious trial aimed to make a difference in the lives of those with mild to moderate COVID-19, and the results could potentially have a lasting impact on the global fight against the virus.

FAS patients had a median age of 53, with 50.2% being female. Most of them (92.1%) had mild COVID-19, and the majority (75.7%) had already been fully vaccinated or boosted. Treatment with VV116 or PAXLOVID was administered within 5 days of symptom onset to 77.3% of patients. High-risk factors found in these patients included 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 aim of this study was to assess the efficacy and safety of a novel therapeutic for COVID-19. The primary endpoint 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 endpoints included progression to severe or critical COVID-19 or death, changes in symptom scores, 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). Results of this study will help determine the effectiveness of this novel therapeutic in treating COVID-19.

After an extensive analysis, it was found that VV116 and PAXLOVID were both noninferior in terms of “time to sustained clinical recovery” for the FAS population (HR = 1.17, 95% CI: 1.02~1.36). Furthermore, the median time to sustained clinical recovery was shorter for the VV116 group compared to the PAXLOVID group (4 days vs. 5 days). This is an exciting discovery that could revolutionize the treatment of FAS patients.

The results of the VV116 group and PAXLOVID group were quite similar, with a median time of 7 days for both “time to sustained resolution of all target symptoms” and “time to a first negative SARS-CoV-2 test”. However, at each preset time point (Days 5, 7, 10, 14, and 28), the proportion of patients with clinical recovery in the VV116 group was larger than that in the PAXLOVID group. Thankfully, there were no reports of progression to severe/critical COVID-19 or deaths in either group.

This study included a large sample of participants, 3/4 of whom had already been vaccinated against SARS-CoV-2. Although most trials exclude such patients, subgroup analysis in this study revealed that there was no significant difference between the treatment results of VV116 and PAXLOVID in either the vaccinated or unvaccinated population.

The safety profile of VV116 was more favorable than PAXLOVID; patients in the VV116 group experienced fewer all-grade AEs (67.4%) and Grade 3 or 4 AEs (2.6%) than patients in the PAXLOVID group (77.3% and 5.7%, respectively).

PAXLOVID stands out from other drug treatments due to its potential to interact with multiple drugs, whereas VV116 is comparatively less likely to interact with other drugs due to its lack of inhibition or induction of major drug-metabolism enzymes, or inhibition of major drug transporters. As a result, VV116 may be the preferable choice for combination therapy.

About VV116 (JT001)

VV116 is an oral nucleoside analog drug that could be a potential game-changer in the fight against SARS-CoV-2. Preclinical studies have suggested that VV116 has a powerful antiviral effect, with a low dose capable of reducing virus titers to below the detection limit and preventing lung injury in mice models. In addition, VV116 has high oral bioavailability and is quickly metabolized into parent nucleoside and distributed throughout the body. If proven effective in clinical trials, VV116 could be a major breakthrough in the fight against the novel coronavirus.

VV116, a joint development 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., and Junshi Biosciences, is set to revolutionize the medical landscape with its clinical development and industrialization. With a global reach, apart from five Central Asian countries, Russia, North Africa and the Middle East, VV116 promises to be a gamechanger in the industry.

Junshi Biosciences and Vigonvita have achieved remarkable success in their studies of VV116, a drug designed to treat patients diagnosed with moderate to severe COVID-19. The companies 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). Their research results have been published in prestigious medical journals such as Acta Pharmacologica Sinica and NEJM. In a remarkable feat, VV116 was approved in Uzbekistan in 2021, making it the first drug to be approved for the treatment of moderate to severe COVID-19.

About Junshi Biosciences

Founded in 2012, Junshi Biosciences is an award-winning biopharmaceutical company that is pioneering innovative treatments for cancer, autoimmune, metabolic, neurological, and infectious diseases. With over 50 drug candidates in its R&D pipeline, the company has achieved remarkable success in introducing the anti-PD-1 monoclonal antibody, the first-in-human anti-BTLA monoclonal antibody, and the anti-PCSK9 monoclonal antibody, which has been approved for clinical trials by the FDA, NMPA, and other regulatory bodies. As a leader in its field, Junshi Biosciences is paving the way for revolutionary treatments and cures.

In the face of the global pandemic, Junshi Biosciences responded immediately, 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, they prioritized and accelerated COVID-19 research and development. Their efforts have resulted in the Emergency Use Authorization (EUA) of JS016 (etesevimab), China’s first neutralizing fully human monoclonal antibody against SARS-CoV-2, in over 15 countries and regions worldwide. To date, more than 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. Additionally, their new oral nucleoside analog anti-SARS-CoV-2 drug, VV116, is currently in global Phase III clinical trials; a testament to their unwavering commitment to innovation for disease control and prevention.

Junshi Biosciences is a rapidly growing global enterprise with a workforce spanning the United States and China. Our presence in America is made up of 3,100 employees across two locations in San Francisco and Maryland, while in China, our presence is spread across five cities, including Shanghai, Suzhou, Beijing, and Guangzhou.

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