By Charles Craig
Agouron Pharmaceuticals Inc. released Phase II/III data Thursday showing its HIV protease inhibitor, Viracept, proved most effective in fighting the AIDS virus when used in combination with two reverse transcriptase inhibitors, AZT and 3TC.
The findings are from one of three Phase II/III trials submitted to the FDA in December 1996 in Agouron's new drug application for Viracept.
The three trials tested Viracept alone; with d4T, a reverse transcriptase inhibitor made by Bristol-Myers Squibb, of New York; and with AZT and 3TC, which are sold by Glaxo Wellcome plc, of London. 3TC was developed by Biochem Pharma Inc., of Laval, Quebec, in collaboration with Glaxo.
In all three trials, Agouron officials said Viracept, given at two dose levels, achieved statistical significance in reducing viral load and raising immune system CD4 cell counts * the two markers against which all AIDS drugs are judged for effectiveness.
In the 308-patient study involving AZT and 3TC, Viracept and the reverse transcriptase inhibitors, also called nucleoside analogues, were evaluated against a combination of AZT and 3TC.
After six months, the triple drug therapy achieved mean reductions of virus in the blood of greater than 99 percent compared with mean reductions of about 95 percent for the AZT and 3TC therapy. Mean increases in CD4 cells reached 160 cells for the triple therapy compared with 105 cells for the dual therapy.
In 80 percent of patients receiving the higher of two Viracept doses in combination with AZT and 3TC, the amount of HIV in the blood fell below the lowest detectable level. Only 18 percent of those taking AZT and 3TC experienced an equivalent improvement.
Protease inhibitors attack HIV replication near the end of the cycle while reverse transcriptase inhibitors interfere near the beginning.
If cleared for marketing, Agouron's Viracept will compete with three protease inhibitors already on the market.
Considered among Viracept's advantages are lack of serious side effects, more convenient administration and fewer problems interacting with other drugs.
Agouron's new drug application (NDA) for Viracept seeks approval for both tablet and pediatric powder forms of the protease inhibitor.
In October 1996 when Agouron, of La Jolla, Calif., said preliminary findings from the pivotal clinical trials were positive and submission of an NDA would follow during the first quarter of 1997, the company's stock (NASDAQ:AGPH) gained 9 percent, closing at $54.25. (See BioWorld Today Oct. 25, 1996, p. 1.)
Agouron filed the NDA ahead of schedule and its stock continued to climb.
On Tuesday, Agouron and its Viracept development partner, Japan Tobacco Inc., of Tokyo, said Roche Holding Ltd., of Basel, Switzerland, agreed to pay them $40 million to market the drug in Europe. (See BioWorld Today Jan. 22, 1997, p. 1.)
Agouron's shares jumped $5 Wednesday to close at $83.75 and then fell $5.438 Thursday to $78.312. However, on Thursday the stock soared as high as $86 in heavy trading of 1.15 million shares.
Roche's HIV protease inhibitor, Invirase, was the first in that class of drugs approved by the FDA in late 1995. Agouron said preliminary data of a 13-patient trial combining Viracept and Invirase showed median decreases in viral load of 99 percent and median increases in CD4 cells of 118. An expanded study of the dual protease inhibitor therapy is under way. *