Introduction

146 DIRECTED RESEARCH
would be resistant to other protease inhibitors when they came along
The University of Washington’s Collier, who was the study’s principal
investigator, briefly left the room with the Roche representative to discuss
the company’s earlier European studies, whose results had not been
fully released to the committee. 9 “We wanted to make sure there’s an
effective dose, shown to have activity,” said Collier. “A small group of
leaders of the ACTG were shown confidential data that proved we had
an adequate dose that had activity. In the end, there is a limit to the number
of pills any one person can take. The dose was subjected to a lot of
scrutiny—by me, by the ACTG, and by Roche itself.” 10
The committee voted to allow ACTG 229 to move forward. Collier
and her colleagues enrolled 302 patients between March and July 1993
for a twenty-four-week trial that used surrogate markers to evaluate the
various drug regimens. New tests that had recently come on the market
allowed the clinicians to measure not only the level of CD4 cells in the
blood, but the patient’s level of HIV. These viral load tests, as they
became known, were considered a superior indicator. The preliminary
results weren’t released until May 1994 and showed slightly better results
in the three-drug combination than with either AZT alone or in combination
with ddC. “While the results weren’t fabulous compared to what
came later, it was clearly better than we had at the time,” Collier later
said.
Roche management’s failure to fund tests of higher doses of the drug
may have saved the company money in the short run, but its long-term
costs were enormous. Because ACTG 229 used a suboptimal dose of
saquinavir, the scientific community lost a golden opportunity to obtain
early knowledge of the potential effectiveness of triple-combination
therapy.
It wasn’t just bad science, it was bad business since the company lost
its first-mover advantage. In the drug industry, the first company to
develop an entry for a new class of drugs—assuming its entry is effective—almost
always gains the lion’s share of the market. But as subsequent
tests would show, saquinavir in its original formulation was not a
very effective drug because of its poor bioavailability.
Fearing Roche would use ACTG 229 to pursue accelerated approval
at the FDA, a coalition of AIDS activist groups centered on the East
Coast asked the agency to hold off on rapid approval for saquinavir. “We
feel that such an approval would penalize people with AIDS/HIV by setting
an inappropriately low standard of evidential requirements that
would govern the regulation of this entire class of therapies,” they wrote