In a Phase II randomized trial, GLQ223 (alpha-trichosanthin)was more effective than either AZT or the combination of AZTand GLQ223 in reducing viral load in patients with AIDS andAIDS-Related Complex (ARC).

However, Genelabs Inc.'s purified form of alpha-trichosanthindid not show a statistically significant advantage in reducingthe rate of disease progression.

Preliminary results of the comparative study were reportedMonday at the 33rd Interscience Conference on AntimicrobialAgents and Chemotherapy (ICAAC) in New Orleans. The trialincluded 148 patients who had been treated with AZT for atleast nine months and had CD4 counts between 200 and 500.They were randomized to either continue receiving AZT, toreceive GLQ223 or to get a combination of the two.

Genelabs' president and chief executive officer, Frank Kung,told BioWorld that the study looked at two endpoints: diseaseprogression, defined as appearance of opportunistic infections,death or reduction of CD4 count more than 25 percent frombaseline; and fivefold reduction in viral load.

With regard to the primary endpoint, Kung said there were fiveconfirmed cases of disease progression in the AZT group, oneconfirmed and two suspected in the GLQ223 group and fiveconfirmed and one suspected in the combination group. The pvalue was .09, which is below the .1 level called for in thestudy design to confirm a trend.

Kung added that the five clinical failures with AZT occurredduring treatment, while the failures with GLQ223 and thecombination occurred outside the treatment period.

Two patients in the GLQ223 treatment group experienced afivefold reduction in viral load, while no one in the othertreatment arms experienced this reduction, for a p value of .02.Baseline viral load was measured by quantitative competitivepolymerase chain reaction (QC-PCR).

Kung said an important finding of the study was that viral loadis a better predictor for disease progression (p value .003),whereas CD4 count is not useful. The rate of CD4 cell declinewas similar in all three treatment arms.

GLQ223 was administered every three weeks in escalatingdoses of 36, 50 and 100 micrograms per kilogram (ug/kg)every other dose, followed by 10 doses of 150 ug/kg everythree weeks for a total of 16 doses. AZT at 500 mg was givendaily in three divided doses. After 102 patients were enrolledthe protocol was modified to give the first four doses weekly.

Reported side effects included flu-like symptoms, allergicreactions and elevations in muscle and liver enzymes, whichGenelabs (NASDAQ:GNLB) of Redwood City, Calif., said wereclinically manageable.

The study was begun in 1991 and the core protocol ended lastmonth. Kung said a complete analysis of the trial will befinished in about three months, and the company then willdecide if it will pursue further clinical development of thedrug. "We remain cautiously optimistic," Kung said.

-- Brenda Sandburg News Editor

(c) 1997 American Health Consultants. All rights reserved.