Junshi Biosciences Announces NMPA Acceptance of NDA for Oral Anti-SARS-CoV-2 Drug VV116 (Deuremidevir Hydrobromide Tablets)

On January 17, 2023 (Beijing Time), Junshi Biosciences (1877.HK, 688180.SH) announced that the National Medical Products Administration (NMPA) had accepted its New Drug Application (NDA) for deuremidevir hydrobromide tablets (product code: VV116/JT001), an oral nucleoside antiviral drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for the treatment of coronavirus disease 2019 (COVID-19).

VV116 is a novel oral nucleoside antiviral drug that non-covalently binds in its triphosphate form to the active site of the SARS-CoV-2 RNA-dependent RNA polymerase, directly inhibiting the enzyme’s activity and blocking the replication of progeny viruses, thereby exerting an antiviral effect. Preclinical studies have demonstrated that VV116 exhibits significant antiviral activity against both the ancestral strain and mutant variants of SARS-CoV-2, including Omicron, with no evidence of genotoxicity.

In November 2021, the Investigational New Drug (IND) application for VV116 was approved by the National Medical Products Administration (NMPA). Subsequent Phase I clinical studies demonstrated that VV116 exhibited satisfactory safety, tolerability, and pharmacokinetic profiles, with rapid oral absorption. A Phase III clinical trial (NCT05341609) evaluating VV116 versus nirmatrelir/ritonavir (Paxlovid) for early treatment of mild-to-moderate COVID-19 in patients at high risk of progression to severe disease (including death) met its prespecified non-inferiority primary endpoint. Compared with Paxlovid, VV116 was associated with a shorter time to clinical recovery (4 days vs. 5 days) and fewer safety concerns. These findings were published in the prestigious global journal The New England Journal of Medicine (NEJM; Impact Factor: 176.079).

On October 21, 2022, the first patient was enrolled and dosed in a multicenter, double-blind, randomized, placebo-controlled, Phase III clinical trial (NCT05582629) evaluating the efficacy and safety of VV116 in patients with mild-to-moderate COVID-19, with or without high-risk factors for progression to severe disease. Led by Academician Li Lanjuan from the School of Medicine, Zhejiang University, the study was conducted across 32 centers in China. The study has completed the prespecified interim analysis, and the Independent Data Monitoring Committee (IDMC) has determined that the prespecified primary efficacy endpoint was met. Junshi Biosciences will release detailed study data at a later date.

VV116 is an oral nucleoside analog that inhibits SARS-CoV-2 replication. Preclinical pharmacodynamic studies have demonstrated that VV116 exhibits significant antiviral activity in vitro against both the original strain and mutant variants of SARS-CoV-2, including Omicron. In mouse models, low doses of VV116 reduced pulmonary viral titers to below the limit of detection, significantly ameliorated pathological changes in lung tissue, and exhibited potent antiviral efficacy. Preclinical pharmacokinetic and other studies indicated that VV116 has high oral bioavailability; following oral absorption, it is rapidly metabolized into the parent nucleoside and widely distributed throughout body tissues.

VV116 was jointly developed by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences; the Wuhan Institute of Virology, Chinese Academy of Sciences; the Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences; the R&D Center for Central Asian Drugs of the Chinese Academy of Sciences / Sino-Uzbekistan Pharmaceutical Science and Technology City (a “Belt and Road” Joint Laboratory under the Ministry of Science and Technology); Lingang Laboratory; Suzhou Wangshan Wangshui Biopharmaceutical Co., Ltd. (Wangshan Wangshui); and Junshi Biosciences. Junshi Biosciences and Wangshan Wangshui jointly undertake the global clinical development and industrialization of this drug, with the cooperation covering all regions worldwide except for the five Central Asian countries, Russia, North Africa, and the Middle East.

Junshi Biosciences and Wangshan Wangshui Have Completed Three Phase I Studies in Healthy Chinese Subjects^[1], and completed one Phase III study in high-risk patients with mild to moderate COVID-19 who have risk factors for progression to severe disease in China^[2](NCT05341609), with the study results published in Acta Pharmacologica Sinica and The New England Journal of Medicine, respectively. Additionally, a Phase III study conducted in patients with mild-to-moderate COVID-19, with or without high-risk factors for progression to severe disease, has completed the prespecified interim analysis per protocol and achieved the prespecified primary efficacy endpoint. In 2021, VV116 was approved in Uzbekistan for the treatment of patients with moderate-to-severe COVID-19.

[References]

[1] Qian, Hj., et al. Acta Pharmacol Sin (2022).

[2] Cao Z, Gao W, Bao H, et al. VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2208822.