Pfizer discontinues capravirine development

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Pfizer announced today that it has discontinued development of its non-nucleoside reverse transcriptase inhibitor (NNRTI) capravirine due to disappointing results in phase II studies.

Capravirine was being developed for treatment-experienced patients, but complex drug interactions with other antiretrovirals together with a lack of impact when the drug was added to protease inhibitor-containing therapy made Pfizer pull the plug on a drug that has been struggling to justify its existence ever since Agouron halted the original phase II studies in 2001 on safety grounds.

Pfizer acquired the drug along with Agouron, but it took nearly two years to work out a development plan for the drug. In February 2005 disappointing results of a phase IIb study were reported at the Conference on Retroviruses and Opportunistic Infections, showing that the drug was no more effective than a placebo in patients with NNRTI resistance when added to nelfinavir (Viracept) and two nucleoside analogues chosen by resistance testing.

Glossary

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

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. 

CCR5

A protein on the surface of certain immune system cells, including CD4 cells. CCR5 can act as a co-receptor (a second receptor binding site) for HIV when the virus enters a host cell. A CCR5 inhibitor is an antiretroviral medication that blocks the CCR5 co-receptor and prevents HIV from entering the cell.

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

receptor

In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a “host” cell), HIV binds to the CD4 receptor and its coreceptor. 

“Data from these phase 2b studies show that capravirine does not offer substantial enough benefit over already available therapies”, said John Mattina, Pfizer’s president of Global Research and Development. “For that reason we can’t justify continued development of this compound. We will redirect resources to progress our other HIV/AIDS therapies.”

Pfizer is working to develop the first drug that can inhibit HIV from using the CCR5 receptor to gain entry to cells. Maraviroc is already in phase III studies.