BACKGROUND/AIMS: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. METHODS: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. RESULTS: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. CONCLUSIONS: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load--and therefore minimizes the risk of adverse events--may result in clinical efficacy should be investigated.
BACKGROUND/AIMS: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. METHODS: We included ten chronic hepatitis Bpatients: four received monotherapy, and six combination therapy with interferon alpha 2b. RESULTS: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. CONCLUSIONS: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load--and therefore minimizes the risk of adverse events--may result in clinical efficacy should be investigated.
Authors: Qiao Wang; Eleftherios Michailidis; Yingpu Yu; Zijun Wang; Arlene M Hurley; Deena A Oren; Christian T Mayer; Anna Gazumyan; Zhenmi Liu; Yunjiao Zhou; Till Schoofs; Kai-Hui Yao; Jan P Nieke; Jianbo Wu; Qingling Jiang; Chenhui Zou; Mohanmmad Kabbani; Corrine Quirk; Thiago Oliveira; Kalsang Chhosphel; Qianqian Zhang; William M Schneider; Cyprien Jahan; Tianlei Ying; Jill Horowitz; Marina Caskey; Mila Jankovic; Davide F Robbiani; Yumei Wen; Ype P de Jong; Charles M Rice; Michel C Nussenzweig Journal: Cell Host Microbe Date: 2020-06-05 Impact factor: 21.023
Authors: Robert L Kruse; Thomas Shum; Xavier Legras; Mercedes Barzi; Frank P Pankowicz; Stephen Gottschalk; Karl-Dimiter Bissig Journal: Mol Ther Methods Clin Dev Date: 2017-08-31 Impact factor: 6.698