Biotech Values

[DewDiligence]

IDX899 paper in the journal Current Opinion in Investigational Drugs:

http://www.ncbi.nlm.nih.gov/pubmed/20112173

›IDX899, an Aryl Phosphinate-Indole Non-Nucleoside Reverse
Transcriptase Inhibitor for the Potential Treatment of HIV Infection

Curr Opin Investig Drugs. 2010 Feb;11(2):237-45.
Klibanov OM, Kaczor RL.
Wingate University School of Pharmacy, Wingate, NC 28174-0159, USA.

Antiretroviral drug resistance is one of the complications of highly active antiretroviral therapy (HAART). Second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) are being developed for use in patients infected with HIV-1 because of the enhanced activity of these inhibitors against viruses that are resistant to the first-generation NNRTIs [i.e. resistant to Sustiva].

IDX899 (GSK-2248761), under development by Idenix Pharmaceuticals Inc and ViiV Healthcare [ViiV is the GSK/PE JV for HIV development: #msg-43254006], is an aryl phosphinate-indole second-generation NNRTI that potently and selectively inhibits wild-type and NNRTI-resistant HIV-1 in vitro. Preclinical data for IDX899 suggest a significantly greater barrier to resistance compared with that of the first-generation NNRTI efavirenz [Sustiva]. Two pathways of resistance have been identified for IDX899 in vitro that include Glu138Lys and Val90Ile/Tyr181Cys mutations.

Pharmacokinetic studies demonstrated that IDX899 exhibits linear, dose-proportional and food-dependent pharmacokinetics [hence the PK/food study currently being conducted by GSK: #msg-44790049]; Cmin concentrations achieved with this drug allow once-daily dosing. In phase I clinical trials, IDX899 reduced HIV-1 RNA and increased CD4+ cell counts in treatment-naïve patients infected with HIV-1. At the time of publication, a phase II clinical trial of IDX899 was being conducted.‹