Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) announced that it has initiated a Phase 1/2 clinical trial with ALN-HBV, a subcutaneously administered investigational RNAi therapeutic for the treatment of chronic hepatitis B virus (HBV) infection. The Phase 1/2 trial will be conducted initially in normal healthy volunteers, and, then, in chronic HBV patients. Initiation of this trial is based on encouraging pre-clinical data presented at the American Association for the Study of Liver Disease annual meeting in November 2015. The Company expects to report initial clinical data from patients in this study in mid-2017.
"We believe ALN-HBV has the potential to become a best-in-class, once-monthly, subcutaneous treatment regimen for the treatment of chronic HBV infection, including patients with both HBeAg-positive and HBeAg-negative disease” said Laura Sepp-Lorenzino, Ph.D., Vice President, Entrepreneur-in-Residence, and Program Leader for Alnylam’s Hepatic Infectious Disease Strategic Therapeutic Area (STAr). “We are encouraged by the pre-clinical results with ALN-HBV demonstrating potent and durable knockdown of plasma HBV surface antigen (HBsAg) in rodent models of HBV infection. High unmet need remains for safe and effective HBV therapies with the potential to produce functional cures after a finite treatment period.”
The Phase 1/2 trial of ALN-HBV is a randomized, single-blind, placebo-controlled study being conducted in three sequential parts. Part A is a single-dose study designed to enroll up to a total of 24 normal healthy volunteers (NHVs). Part B will be a single-dose study designed to enroll up to a total of 28 patients with chronic HBV infection. Part C will be a multi-dose study designed to enroll up to a total of 48 patients with chronic HBV infection. The primary objective of the study is to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-HBV. Secondary objectives include evaluation of pharmacokinetics and clinical antiviral activity for ALN-HBV as measured by its effects on serum HBsAg levels in hepatitis B envelope antigen (HBeAg) positive and negative chronic HBV patients.
ALN-HBV utilizes the company's Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate delivery platform, which enables high potency and durability with a very wide therapeutic index. Clinical results from other investigational RNAi therapeutic programs in Alnylam's pipeline that utilize ESC-GalNAc technology have demonstrated robust target gene knockdown and durability supportive of the potential for monthly, quarterly and, possibly, bi-annual subcutaneous dosing regimens, facilitating the potential for improved patient adherence.
ALN-HBV Pre-clinical DataPre-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 13-week GLP toxicology studies in rat and non-human primates.