Today in London, GlaxoSmithKline (GSK) announced it has acquired exclusive worldwide rights to ONO-4128, a new cellular chemokine receptor (CCR5) antagonist discovered by Japan’s Ono Pharmaceutical Company Limited.
The deal gives GSK exclusive worldwide development, manufacturing and commercialisation rights to ONO-4128 and certain associated compounds. In areas of medicine other than HIV, Ono retains the exclusive rights to develop and commercialise its CCR5 antagonists in Japan, South Korea and Taiwan.
The drug, currently in pre-clinical development, is expected to enter phase I trials in the U.S. in the first half of this year.
Blocking the CCR5 receptor with an antagonist may offer a novel mechanism for inhibiting HIV infection.
Several studies have shown that people with a mutant form of the chemokine receptor CCR5, and to a lesser extent CCR2 and SDF-1, have a slower rate of disease progression than those who do not.
CCR5 has been targeted by drug developers as the most promising site because it is present on the CD4 cells of everyone, whereas the CXCR4 co-receptor is much less common until very advanced stages of HIV infection. Alterations in the pattern of CCR5 expression have also been shown to confer a reduced risk of disease progression, suggesting that blocking this target for viral entry may have benefits.
One potential problem with this approach to HIV treatments is the ability of HIV to exploit a wider range of receptors.
Blocking the CCR5 co-receptor may drive the evolution of HIV towards strains which use the CXCR4 co-receptor. The strains using CXCR4 are associated with more rapid CD4 decline and disease progression, so any selective pressure which encourages the emergence of this strain should be avoided.
Details of other fusion inhibitors in development can be found here.