Another drug bites the dust: Glaxo-Wellcome drop NNRTI

Keith Alcorn
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This article is more than 24 years old.

A once-a-day non-nucleoside reverse transcriptase inhibitor (NNRTI) that looked promising in phase I studies has been dropped by Glaxo-Wellcome because its interactions with other anti-HIV drugs are so problematic.

GW420867X, licensed from Hoechst Marion Roussell in 1997, was dropped because experts felt that its profile as a powerful cytochrome p450 3A4 inducer would make it very difficult to partner with other anti-HIV drugs. Most anti-HIV drugs are metabolised through this route, and drugs that induce cytochrome p450 3A4 metabolism will speed up the clearance of other drugs processed that way.

In order to counteract this process, doses of other drugs would have to be increased, possibly resulting in unacceptable increases in pill burdens and drug-related adverse events.

Glossary

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

phase I

The first stage of human testing of a new drug or intervention, typically involving a small number (10-100) of participants who do not have the condition the drug is intended to treat. Phase I clinical trials evaluate safety, side-effects, dosage and how a drug is metabolised and excreted in the body.

In a statement released this week, a spokesman for Glaxo-Wellcome said that the company was very reluctant to make the decision, and will be actively pursuing the development of other NNRTIs.

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