AIDS TREATMENT NEWS Issue #210, November 4, 1994
"Based on the results from two studies, Searle has decided to halt development of its candidate HIV protease inhibitor SC- 52151. The highly promising results seen in earlier IN VITRO studies were not confirmed in either Searle #005, a clinical study of the use of the compound as monotherapy in people with advanced HIV infection, or ACTG #282, a formulation and dosage study. While well-absorbed into the bloodstream and achieving the desired blood levels, SC-52151 produced no measurable effect on any standard surrogate marker of anti- HIV activity -- CD4, p24 antigen, and PCR RNA -- in patients."
The problem with SC-52151 appears to be unique to the Searle drug, and not to affect other protease inhibitors such as the Merck compound. Searle researchers believe that the drug binds to a protein (AAG) in the blood, and is then removed by the liver. Laboratory tests have shown that adding this protein causes the drug to lose antiviral activity. A similar experiment with the Merck compound did not show loss of activity.
More importantly, other protease inhibitors have shown a striking though temporary drop of viral load in people; the Searle drug produced no such effect. This means that we already know the other drugs will not fail in the same way as SC-52151 did.
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