IL-12 studies back on track.

Last June, the U.S. Food and Drug Administration halted a test of the promising anticancer and anti-AIDS drug interleukin-12 (IL-12) after two patients died and several others suffered severe side effects from dosages previously demonstrated to be safe. At the time, scientists at the company conducting the study, Genetics Institute in Cambridge, Mass., speculated that the long-acting form of the drug may have caused the toxic effects (SN: 6/17/95, p.375).

Now, after animal studies, the researchers conclude that the problem lies not in the formulation but in the timing of doses. In the original clinical trials, one dose of IL-12 was given to patients so researchers could determine how fast the body eliminated it. After a few weeks, the volunteers took various doses regularly-once a day, for example. In the halted trial, researchers gave participants, who suffered from kidney cancer, a high, but presumed tolerable, regular dose from the outset.

In tests, the company scientists found that for unknown reasons they had to prime the animals with a single dose of IL-12 a few weeks before starting them on a multiple-dose schedule of the drug. Presented with these results on Oct. 18, FDA lifted the clinical hold on the trial. The company resumed human trials of IL-12 for cancer and AIDS last month.

"We are still investigating why this schedule effect is taking place," says company spokeswoman Gina Brazier. "It has never been seen before in any drug."