Interim results from one of the ongoing phase II studies of RG-101 for the treatment of hepatitis C virus infection ( HCV ) were announced.
The study was designed to evaluate a shortened, 4-week treatment regimen containing a subcutaneous administration of 2 mg/kg of RG-101 at day 1 and day 29, in combination with 4 weeks of once/daily approved anti-viral agents Harvoni ( Ledipasvir, Sofosbuvir ), Olysio ( Simeprevir ), or Daklinza ( Daclatasvir ).
The study enrolled 79 treatment naïve genotype 1 and 4 HCV patients ( Harvoni arm, n=27, Olysio arm, n=27, Daklinza arm, n=25 ).
Thirty-eight patients have been evaluated through 8 weeks of follow up. Ninety-seven percent of those patients ( 37/38 ) had HCV RNA viral load measurements below the limit of quantification.
To date, RG-101 has been generally well tolerated with the majority of adverse events considered mild or moderate, and with no study discontinuations.
For those patients through 12 weeks of follow-up, 100% remained below the limit of quantification ( 14/14 ).
RG-101 is a GalNAc-conjugated anti-miR targeting miR-122 for the treatment of HCV. In a completed phase I human proof-of-concept study, the treatment with a single subcutaneous dose of RG-101 as monotherapy resulted in significant and sustained viral load reductions in all treated HCV patients, including patients with difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen.
microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 800 microRNAs have been identified in the human genome, and over two-thirds of all human genes are believed to be regulated by microRNAs.
A single microRNA can regulate entire networks of genes. As such, these molecules are considered master regulators of the human genome.
microRNA expression, or function, has been shown to be significantly altered or dysregulated in many disease states, including oncology, fibrosis, metabolic diseases, immune-inflammatory diseases and HCV.
Targeting microRNAs with anti-miRs, chemically modified, single-stranded oligonucleotides, offers a unique approach to treating disease by modulating entire biological pathways and may become a new and major class of drugs with broad therapeutic application. ( Xagena )
Source: Regulus Therapeutics, 2016