BI-RG-587: New Antiviral Ready for Trials?

A December 7 report in Science1 on laboratory and animal
tests of a new AIDS antiviral has generated more than usual
interest. Many AIDS laboratory findings appear in technical
journals and are then picked up by the press, but most are not
heard from again. The reason for the greater interest in this
drug seems to be that the major practical bases have been covered
well. With luck, U. S. human trials could begin by early or mid
1991.

The antiviral, named BI-RG-587, was found by a systematic
strategy for synthesizing and screening chemicals likely to be
active against HIV-1 reverse transcriptase (RT), but without the
toxicity of the nucleoside analog RT inhibitors such as AZT, ddC,
and ddI. BI-RG-587 inhibited several strains of HIV-1 at low
concentrations (under 50 nM) in cell cultures. Over 8,000 times
the concentration was needed to be toxic to human cells. The
chemical was so specific to HIV-1 that it had no effect on HIV-2,
or on any other virus tested; this great specificity may help to
reduce side effects. BI-RG-587 was also effective against HIV-1
strains obtained from four patients using AZT; we do not know the
concentration used in these tests.

In animals, BI-RG-587 could be given orally. In monkeys, a
single dose produced plasma levels 35 to 140 times the
concentration needed to inhibit HIV-1 in the cell-culture tests,
and these levels were maintained during an eight-hour period. In
chimpanzees, 600 times the required concentration was achieved.
The drug did cross the blood-brain barrier very well in the
animal tests.

BI-RG-587 is a simple molecule which appears not difficult
to synthesize -- important so that if it proves effective, there
will not be delays due to manufacturing problems.

The developer of BI-RG-587 -- Boehringer Ingelheim
Pharmaceuticals, Inc., Ridgefield, Connecticut -- was not
previously known to be working on AIDS. However, rumors were
furiously circulating shortly before the December 7 announcement,
suggesting that the German parent company was starting tests of
an AIDS drug.

AIDS TREATMENT NEWS has learned that the U. S. company has
plans to file an IND (Investigational New Drug application) in
January 1991, and has hopes of starting a U. S. trial by March.

Despite encouraging laboratory results, only human trials
can tell if the drug will work. Another non-nucleoside RT
inhibitor -- a TIBO derivative, the first one tested in humans --
showed similar promise in laboratory and animal tests, but seems
not to be effective in patients. Other companies also are
developing their own lines of non-nucleoside RT inhibitors. No
one knows in advance which ones will be successful. But what can
be done is to make sure that there are no unnecessary obstacles
or delays in finding out.

References

1. Merluzzi VJ, Hargrave KD, Labadia M, and others. Inhibition
of HIV-1 Replication by a Nonnucleoside Reverse Transcriptase
Inhibitor. Science. December 7, 1990; volume 250, pages 1411-
1413.