Searle Abandons Its Protease Inhibitor

In a November 4 conference call, Searle announced that it was
stopping development of its protease inhibitor SC-52151,
saying that despite promising results in laboratory tests,
two clinical trials have shown no indication of antiviral
activity in people. The company issued the following
statement:

"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.