PI Perspective #46

September 2008     View PDF     En español

Two new NNRTIs enter the pipeline

by Paul Dalton

Data on two novel NNRTIs were presented at today’s late-breaker session at the International AIDS Conference. After years with little development for this important class of HIV treatments, news on two somewhat promising compounds is welcome.

IDX899
IDX899 is being developed by Idenix, a small pharmaceutical company based in Cambridge, MA. Carlos Zala presented data from a small Phase I proof-of-concept study. A total of 30 people were given either a placebo or 1 of 3 doses (200, 400 or 800mg once daily) for seven days.

At the end of the study, people taking IDX899 experienced drops in their viral loads between 1.73 and 1.82 logs, while those taking placebo saw their viral loads rise slightly. The differences among the different doses were not significant.

Interestingly there was also not a strong relationship among the different doses given and the levels of drug measured in the body. When asked by an audience member to explain this, Dr. Zala had no clear explanation, but he pointed out that the levels were consistently far above those necessary to inhibit replication of HIV. This led the company to open another arm of the study, looking at a 100mg dose. No data on that group were presented.

There were few adverse events reported in the study, including no incidence of rash or neurological changes. However, the study was very small and short-term. More information will come out in larger studies being planned.

RDEA806
RDEA806 is an experimental NNRTI being developed by Ardea Biosciences of San Diego, CA. Graham Moyle presented data from a Phase IIb dose ranging study of 48 people who had never taken HIV drugs. People took either a placebo, 400 or 600mg twice a day, or 800 or 1000mg once a day for 7 days.

At the end of the study, people taking all of the doses of RDEA had lower HIV levels of between 1.7 and 2.0 logs, where people taking the placebo saw a small increase. Overall the drug was well tolerated with few adverse events reported.

One of the potential drawbacks for this drug is the relatively high doses being studied for once daily use. One audience member asked how it would compete with rilpivarine, another experimental NNRTI closer to possible approval. Moyle pointed out that rilpivarine had several hurdles to overcome and the company would evaluate the future of their drug in this light.

Commentary
The NNRTI class has long been dominated by Sustiva. It is good news to see several new drugs with promising properties, like good potency and tolerability. These two drugs are very early in development, so much more research will be done before we know whether either will be a good option for people with HIV. Nonetheless, with the pipeline as thin as it is, all good news on new HIV drugs is welcome.