Suzhou Ribo Life Science Co., Ltd. recently announced the completion of "A randomized, double-blind, placebo-controlled, single-dose escalating Phase I clinical study to evaluate the safety and pharmacokinetics of RBD1016 in healthy subjects" of its Class 1 siRNA drug for chronic hepatitis B in Australia.
The study was the first-in-human (FIH) clinical trial of RBD1016 based on Ribo´s proprietary GalNAc-siRNA platform. The study randomized 32 healthy subjects in the 4 dose groups enrolled. No serious adverse events (SAE) or adverse events of special interest (AESIs) were observed. All drug-related adverse events were determined to be mild in the study. The results of the clinical study showed that RBD1016 exhibited a good safety and tolerability profile, which are on par with other investigational anti-hepatitis B siRNA drugs. In addition, the human pharmacokinetic profile of RBD1016 obtained from the clinical study was consistent with the data in preclinical animal models, where best-in-class efficacy data was demonstrated previously.
Further to this clinical study, Ribo has initiated "A randomized, double-blind, placebo-controlled, single and repeated dose escalation, phase I clinical study to evaluate the safety, pharmacokinetics and preliminary pharmacodynamics of RBD1016 in subjects with chronic hepatitis B virus (HBV) infection" in Hong Kong, China. The study is progressing according to plan, with the completion of enrollment and dosing of the first 2 dose cohorts.
About Viral Hepatitis B (viral hepatitis type B)
Viral hepatitis B is an infectious disease caused by the hepatitis B virus, mainly liver lesions, and is one of the most significant infectious disease threats in the world, with nearly 300 million infections worldwide. China has the most severe disease burden of hepatitis B in the world, with 28 million chronic hepatitis B patients. Only about 3.5 million of the HBV-infected people who should be receiving treatment are under treatment. According to China's hepatitis B treatment guidelines, the ultimate goal for treating chronic hepatitis B is clinical cure (functional cure), in which HBsAg (hepatitis B surface antigen) remains negative (with or without the presence of anti-HBs (antibodies to hepatitis B surface antigen), HBV DNA undetectable, liver biochemistry indices normal, and liver histopathology improved after stop of treatment. Current treatments include nucleoside analogs (NAs) and interferons, but functional cure is yet difficult to achieve. Hepatitis B drug development is mainly based on the sustained clearance of HBsAg, a primary indicator for functional cure, and the reduction of HBsAg is the main challenge for clinical treatment of hepatitis B at this stage. Therefore, it is urgent to develop an anti-hepatitis B virus drug that effectively reduces HBsAg with good safety profile and can achieve functional cure.
RBD1016 is an anti-hepatitis B GalNAc-siRNA drug independently developed by Ribo. Preclinical studies showed that RBD1016 can not only inhibit HBV DNA replication, but also reduce HBsAg more effectively with long duration. RBD1016 is the only anti-hepatitis B siRNA drug in the world, according to the publically available information, which demonstrated serological conversion in animal models, indicative of its potential for functional cure for hepatitis B
RBD1016 has demonstrated well tolerated safety profile and pharmacokinetic characteristics expected for GalNAc-siRNA in the first human clinical study, which validated Ribo's GalNAc-siRNA liver-targeting delivery technology and oligonucleotide therapeutic platform. Ribo expects more oligonucleotide drug products entering clinical stage in 2022.