Date: 2014-11-11
Type of information: Initiation of development program
phase:
Announcement: initiation of a development program - presentation of data at the TIDES 2014 meeting
Company: Alnylam Therapeutics (USA - MA)
Product: ALN-HBV
Action
mechanism: ALN-HBV is an RNAi therapeutic targeting the HBV genome in development for the treatment of HBV infection. In pre-clinical study results presented at the TIDES 2014 meeting, Alnylam reported significant, multi-log reductions in HBsAg and HBV viral titers in chronically infected chimpanzees.
Disease: hepatitis B
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On November 11, 2014, Alnylam Pharmaceuticals announced that the company continues to advance its ALN-HBV program, in development for the treatment of hepatitis B viral infection; the company remains on track to select a Development Candidate (DC) by the end of the year and expects to file an investigational new drug (IND) application or IND equivalent around the end of 2015. Alnylam plans to advance ALN-HBV as an ESC-GalNAc-siRNA conjugate which should enable once monthly subcutaneous dose administration with potent and durable effects, and a wide therapeutic index. The company remains on track to select a development candidate in late 2014 and plans to file an IND or IND equivalent around year-end 2015. * On May 12, 2014, Alnylam Pharmaceuticals, a leading RNAi therapeutics company, announced that it has named a new program to its pipeline: ALN-HBV for the treatment of hepatitis B virus (HBV) infection.The company reported significant, multi-log reductions in HBV surface antigen (HBsAg) and HBV viral titers, and showed evidence for an immune-mediated therapeutic effect in chronically infected chimpanzees. The new data are being presented at the TIDES 2014 meeting, being held May 12 – 15 in Providence, Rhode Island. The results were from a model of chronically infected chimpanzees (N=4) showing that RNAi therapeutics targeting a conserved region of the HBV genome could have the potential of achieving a functional cure. First, potent siRNAs that target highly conserved regions of the HBV genome were designed and synthesized. When administered as a single 0.25 mg/kg dose in a lipid nanoparticle (LNP) formulation in chronically infected chimpanzees, the RNAi therapeutic showed an over 2 log10 reduction in circulating viral DNA in the highest titer animal and a mean 1.9 log10 decrease in viral DNA. These effects were confirmed to be RNAi specific by use of a control LNP-encapsulated siRNA, and to be mediated by an RNAi mechanism of action as detected by 5’RACE. In multi-dose, dose-escalation studies in the chronically infected animals, doses of 0.125 to 0.5 mg/kg achieved an over 4 log10 reduction of circulating viral DNA and an up to 2.3 log10 reduction in HBsAg; a mean 2.9 log10 reduction and a mean 2.0 log10 reduction were achieved in HBV DNA and HBsAg, respectively. In one animal with greater than five-fold elevated alanine aminotransferase (ALT) levels at baseline, administration of the RNAi therapeutic was associated with a complete normalization of elevated transaminase levels. Of interest, two of four animals showed mildly elevated liver transaminase levels of about two-to-three fold approximately one-to-two months post dosing that included increases in interferon-gamma and interleukin-6, suggestive of potential “therapeutic flares” related to immune clearance of infected hepatocytes. Alnylam plans to advance an ESC-GalNAc-siRNA conjugate targeting the HBV genome for its ALN-HBV program. An ESC-GalNAc-siRNA conjugate will enable subcutaneous dose administration with improved potency and durability, and a wide therapeutic index. The company expects to select a Development Candidate (DC) in late 2014 and plans to file an IND or IND equivalent around year end 2015.
