15 Nov, 2015 Pre-Clinical Results from ALN-HBV for the Treatment of Hepatitis B Virus Infection
We presented new pre-clinical data with ALN-HBV, an investigational RNAi therapeutic targeting the Hepatitis B Virus (HBV) genome for the treatment of HBV infection. The ALN-HBV siRNA targets a highly conserved site across genotypes A-J, mapping to the X open reading frame, which is downstream from the most prevalent integration hotspot targeted by siRNAs from other developers. ALN-HBV is thus expected to achieve potent knockdown of HBV surface antigen (HBsAg) expressed by both covalently closed circular DNA (cccDNA) and integrated HBV DNA. Pre-clinical study results in rodent HBV models showed that subcutaneous administration of ALN-HBV led to potent and durable knockdown of HBsAg. Single doses of ALN-HBV in mice resulted in an up to 3.6 log10 and a mean of 1.6 log10 reduction of HBsAg 15 days after a single dose. Further, multiple doses of ALN-HBV in rats showed highly durable knockdown, with effects lasting up to 4 months following three weekly doses of ALN-HBV at 3 mg/kg. In addition, ALN-HBV was generally well tolerated in all rodent models.
We are encouraged by these pre-clinical results demonstrating the potential of ALN-HBV to achieve potent and durable HBV target silencing and plasma HBsAg knockdown. There is a high unmet need for safe and effective HBV treatments with infrequent dosing for improved patient adherence. We look forward to additional data from this program and intend to continue working toward a potential functional cure for patients with chronic HBV infection.