Junshi Biosciences announced publication of Phase 3 result on New England Journal (NEJM) for VV116 Versus PAXLOVID for Adults at High Risk for Progression to Severe COVID-19
Shanghai Junshi Biosciences Co., Ltd, a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced on December 29, 2022 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 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 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. 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, 2022, 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.
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 studies. 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 therapy.
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.