Journal Article

Single-dose suraxavir marboxil for acute uncomplicated influenza in adults and adolescents: a multicenter, randomized, double-blind, placebo-controlled phase 3 trial

Ma, Anlin, Ding, Yan, Wang, Yeming, Cao, Zhaolong, Zhang, Yu, Yu, Yunsong, Ge, Fangqi, Wang, Shaofang, Chen, Xuyan, Yang, Guoru, Feng, Ganzhu, Liu, Dong, Wang, Sikui, Xiao, Zuke, Wei, Jun, Li, Xing, Cao, Bin, Deng, Min, Li, Xiaoguang, Sun, Yilan, Wang, Hong, Liu, Yuanyuan, Liu, Chuanmiao, Wu, Xiaoping

2025

Overview

Suraxavir marboxil (GP681) is an antiviral drug inhibiting the polymerase acidic protein (PA) of RNA polymerase, of influenza. It has shown therapeutic activity against influenza A and B virus infections in preclinical studies. In this multicenter randomized, double-blind, placebo-controlled, phase 3 trial, we aimed to investigate the efficacy and safety of single-dose suraxavir marboxil (40-mg oral dose) in otherwise healthy outpatients aged 5–65 years with uncomplicated influenza unaccompanied by severe issues. From 28 July 2022 to 31 October 2023, 591 outpatients aged 5–65 years with uncomplicated influenza underwent randomization in 46 research centers in China and were randomly assigned in a 2:1 ratio to receive suraxavir marboxil (40 mg) or placebo within 2 days of symptom onset. The primary outcome was time to alleviation of influenza symptoms (TTAS) (from the start of treatment until body temperature returned to 37.2 °C or less and all seven influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) resolved for at least 21.5 h) within 15 days by treatment. The secondary endpoints included virological indicators, system and respiratory symptoms, PA variant mutation and adverse events. The median TTAS was significantly shorter in the group that received suraxavir marboxil compared to the placebo group (42.0 h versus 63.0 h, P  = 0.002). Suraxavir marboxil was associated with more rapid decrease in viral load from baseline than placebo by 1 day after administration, with a mean change of −2.2 ± 1.3 compared to −1.3 ± 1.7 log 10 copies per ml ( P  < 0.001) in the placebo group. Adverse events were reported in 28.4% (112 of 395) of suraxavir marboxil recipients and 23.3% (45 of 193) of placebo recipients, most of which were mild or moderate. The incidences of PA variants with the I38T mutation in the H1N1pdm and H3N2 subtypes were 0.7% (1 of 138) and 0.9% (2 of 213), respectively. Low acquired drug resistance was observed. In this trial, timely single-dose suraxavir marboxil was effective in shortening TTAS and reducing the influenza viral load in patients aged 5–65 years with uncomplicated influenza safely. ClinicalTrials.gov registration: NCT05474755 . Suraxavir marboxil, an antiviral drug designed to inhibit the polymerase acidic protein of influenza, alleviates symptoms in individuals with influenza faster than placebo in a phase 3 trial conducted in China.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/2779/777 / 692/699/255/2514 / Adolescent / Adolescents / Adult / Adverse events / Aged / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / Antiviral Agents - therapeutic use / Antiviral drugs / Arthralgia / Biomedical and Life Sciences / Biomedicine / Body temperature / Cancer Research / Child / Child, Preschool / Chills / China / Cough / DNA-directed RNA polymerase / Double-Blind Method / Drug dosages / Drug resistance / Effectiveness / Female / Headache / Humans / Infectious Diseases / Influenza / Influenza A / Influenza, Human - drug therapy / Influenza, Human - virology / Male / Metabolic Diseases / Middle Aged / Molecular Medicine / Muscular fatigue / Mutation / Neurosciences / Pharyngitis / Placebos / Proteins / Randomization / Research facilities / RNA polymerase / RNA viruses / Treatment Outcome / Viral Load - drug effects / Young Adult