Idenix Pharmaceuticals (IDIX)

[DewDiligence]

Nucleoside vs Nucleotide in HBV

In the treatment of HBV, there has been a lack of data to justify combination therapy. A presentation at the 2006 AASLD conference showed that the mutant strains of HBV that emerged from treatment with Lamivudine increased the likelihood of a given patient’s developing resistance to Baraclude; this happened because the strains resistant to Baraclude were found to be a proper subset of the strains resistant to Lamivudine (#msg-14399529).

If, for example, Lamivudine and Baraclude were to be given as part of an HBV combination regimen, a likely outcome would be to expedite resistance to both drugs, rendering such a combination counter-productive. The same may hold for other combinations of nucleoside drugs including combinations with Tyzeka.

Many observers consider HBV combination therapy using a nucleoside and a nucleotide to be a more promising approach than combination therapy using two nucleosides or two nucleotides. (Please see #msg-16968764 for the structural difference between a nucleoside and a nucleotide.)

The main nucleotide drugs for HBV are Hepsera and Viread. (Viread, the HIV blockbuster from GILD, is not yet approved for HBV, but it almost certainly will be in 2008.) Another nucleotide candidate for HBV is ANA380 from ANDS, but the ANA380 program appears to be on life support (#msg-19355016).