Early Stage HIV Pipeline at GlaxoSmithKline Aimed at Combating Resistance

PARIS -- Presentations this week at the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment continue to demonstrate GlaxoSmithKline's commitment to developing new compounds designed to combat HIV infection. Data were presented on three of many key HIV compounds currently under investigation in the GSK pipeline.

Researchers described details of an investigational aspartyl protease inhibitor (PI) known as 640385 (VX-385). The compound has shown activity in vitro against the HIV virus, including strains resistant to multiple protease inhibitor drugs.

Data presented at the conference indicate 640385 has an IC50 of 1.1nM against wild type virus, and retained activity against 65 percent of a panel of 55 clinical isolates that are phenotypically resistant to multiple PIs (median number of drug-resistance mutations per isolate was 8). Researchers cautioned that the in vitro results will need to be explored in clinical trials, which are now underway. 640385 was jointly discovered by GlaxoSmithKline and Vertex Pharmaceuticals, and is now in Phase I clinical development.

A non-nucleoside reverse transcriptase inhibitor (NNRTI), 678248, was selected for clinical development due to its potency, as evidenced by strong in vitro activity in the nanomolar range against HIV isolates resistant to currently available NNRTIs. Data were presented that characterized the antiviral activity of the compound, including the selection of resistance and activity against clinical isolates from NNRTI-experienced patients. This new generation compound was discovered by GSK.

In addition to these two Phase I compounds, GSK has recently entered Phase I development with a cellular chemokine receptor (CCR5) antagonist, 873140 (ONO-4128). The CCR5 receptor is believed to be the predominant co-receptor used by HIV in the early and middle stages of infection. Blocking the CCR5 receptor with an antagonist may be an alternative mechanism for inhibiting HIV infection of CD4 cells in humans. Data from the conference on the receptor binding profile of this compound support its further evaluation. Dr. Kenji Maeda, working in conjunction with Dr. Hiroaki Mitsuya at Kumamoto University School of Medicine, Kumamoto, Japan, presented the data.

"Of the 40 million HIV-infected individuals in the world, a large proportion has developed viral resistance to currently available medicines, making resistance a growing issue in the field of HIV that will need to be addressed into the next decade," said Ken Batchelor, senior vice president, Metabolic and Viral Diseases, GSK. "We recognize that there is a pressing need for new anti-HIV drugs in existing and new pharmacologic classes with limited cross-resistance. Our aim is to meet this need with continued research and development of HIV therapies."

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Source: GlaxoSmithKline

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