A new RNAi treatment candidate for chronic hepatitis B (HBV) infection called ALN-HBV, has entered a Phase 1/2 clinical trial to evaluate its safety and efficacy in healthy volunteers and HBV patients.
The study was initiated based on positive pre-clinical data presented in 2015 at the American Association for the Study of Liver Disease. Alnylam Pharmaceuticals expects to report preliminary data from the trial 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, PhD, vice president and program leader for Alnylam’s Hepatic Infectious Disease Strategic Therapeutic Area, in a press release. “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.”
RNAi, (RNA interference) refers to technology that promotes a naturally occurring process used by cells in all living things to turn off, or silence, genes when a virus invades a cell.
Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate delivery platform was used to improve the efficacy and durability of ALN-HBV. Other RNAi therapies that used the platform show that the technology improves the durability of the RNAi which might allow for monthly, quarterly, and even bi-annual dosing regimens.
In preclinical studies, the drug’s injection in mice with HBV showed potent and durable knockout of the infection. The same was observed in rats, where three weekly doses injections eliminated the signs of infection for up to four months.
The new randomized, single-blind, placebo-controlled study will evaluate ALN-HBV in three distinct parts. In part A, a single dose will be evaluated in 24 healthy volunteers. Part B will also evaluate single doses of the drug, but in 28 patients with chronic HBV infection. In part C, 48 HBV patients will be enrolled in a multi-dose study.
The study was designed to evaluate the safety and tolerability of single and multiple injected dose regimens of ALN-HBV. Other objectives include the assessment of clinical antiviral activity and how ALN-HBV works it the body through measurements of HBsAg serum levels in hepatitis B envelope antigen (HBeAg) negative and positive HBV patients.