The Body Covers: The 12th Conference on Retroviruses and Opportunistic Infections
Safety and Pharmacokinetic Data for 640385, a New Protease Inhibitor in Development
February 24, 2005
In July 2003, during the 2nd International AIDS Society Conference on Pathogenesis and Treatment, which was held in Paris, France,1 data were presented about the in vitro anti-HIV activity of a new protease inhibitor (PI) called 640385 (also known as VX-385 or GW0385). This drug, which is being developed by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals, demonstrated antiviral activity against PI-resistant HIV.Reference Abstract: 640385, a novel HIV-1 protease inhibitor: safety and pharmacokinetics following repeat administration with and without ritonavir in healthy subjects (Poster 563)
Another presentation about 640385 came during the International AIDS Conference in Bangkok, Thailand, where we learned that 640385 appears to select for a mutation at A28S, which is quite unique among the mutations associated with PI resistance.
Susan Ford's presentation represents the first study to my knowledge in which regular human beings have received this new medicine. This phase 1 study looked at a dose escalation in healthy volunteers. The goal of this type of study is to test the maximum well-tolerated dose of a drug and gain information about the drug's pharmacokinetics. Six different doses were tried, and each one, as expected, had different pharmacokinetic characteristics.
The good news is that 640385 seemed reasonably well tolerated and the side effects were mild. The not so good news is that it seems that this compound will need to be dosed in combination with ritonavir (RTV, Norvir) as part of a boosted combination because the drug levels in the blood were relatively modest when given alone. This is not a big surprise since most PIs have to be dosed this way, but one secretly hoped that one day there would be a PI that would not require boosting (I guess I am still upset at Abbott about the dramatic price increase of ritonavir 1 year ago).
One of the highlights of CROI was the presentation of the case of a New York City patient with multidrug resistant virus.2 It is drugs like 640385 that, when they become available, will be able to help patients like this unfortunate man from New York.
Hopefully, we will soon have additional data about the clinical potential of this drug. We'll have to wait until this medicine is given to HIV-infected patients. I also hope that 640385 will have a "real" name soon. It is difficult to keep up with all these numbers.
Authored by: S Ford, S Reddy, M Anderson, S Murray, J Ng-Cashin, M Johnson
Affiliations: GlaxoSmithKline, Research Triangle Park, NC, USA
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