WASHINGTON _ Chiron Corp.'s drug for kidney cancer,interleukin-2 (IL-2), also appears capable of boosting the immunesystem of some HIV-infected patients, according to a recent early-stage study. Experts said the results could represent a promising newapproach to AIDS _ that of modifying the immune system ratherthan just attacking the virus.

Researchers at the National Institute of Allergy and InfectiousDiseases (NIAID) tested IL-2 in an uncontrolled Phase II trial of 25HIV-infected patients and published their findings in today's issue ofThe New England Journal of Medicine. The drug, a recombinantform of the natural regulatory cytokine, was administered as acontinuous infusion (at varying doses) every day for five days ateight-week intervals during a period of seven to 25 months. Patientsin the study also received standard anti-viral therapy.

In the 10 patients who entered the study with CD4 counts higher than200, six experienced a 50 percent increase in CD4 cells at one andtwo months after infusion. The higher CD4 counts could be sustainedand reinduced with new injections and, to date, there is no evidenceof drug resistance.

However, for the 15 patients in the study who had CD4 counts of 200or less, IL-2 therapy was associated with increased viral activation,few immunologic improvements, and substantial toxic effects.

Indeed, IL-2 therapy for HIV-infected patients may be hampered bythe drug's dose-limiting side effects. Patients in the NIAID studysuffered from "severe influenza-like symptoms," hepatic and renaldysfunction and edema, among other things. "There's no doubt thatduring the five days [of drug infusion], a lot of the patients feelmiserable," Henry Masur, one of the study's authors and chief of theCritical Care Medicine Department at the National Institutes ofHealth (NIH), told BioWorld.

Most AIDS drugs are evaluated in early tests, such as Phase I and IIstudies, on the basis of their activity against so-called "surrogatemarkers" of the disease, rather than for their ability to impactsurvival. The two most prominent markers used are changes in CD4cells (critical immune system cells) and changes in the number ofvirus particles in the blood (viral load).

Based on logic and intuition, scientists have hypothesized thatboosting CD4 cells and decreasing viral load are desirabletherapeutic goals. However, manipulating levels of these two markersin a patient's blood, either transiently or for a sustained period, hasnot yet been shown to extend life or produce concrete clinicalbenefits (i.e., prevent or reduce the frequency of opportunisticinfections).

"The next big leap for this drug is to show that it improves the qualityand extends the duration of a patient's life," said Masur, adding thatIL-2 will need to be evaluated in a roughly 3,000-patient randomized,controlled Phase III trial to find out what effect it has on clinicallyrelevant endpoints.

One curious and difficult-to-interpret finding of the NIAID's IL-2study was the drug's impact on viral load levels in patients. Four ofthe 10 patients with higher baseline CD4 counts had a transient butconsistent increase in viral load at the end of each infusion. That'sobviously a change in the opposite direction from what scientiststhink is a good idea.

"The clinical importance of the transient burst in viral RNA [viralload] after an infusion of interleukin-2 is uncertain," wrote thestudy's authors.

Among the 15 patients with lower baseline CD4 counts, IL-2 not onlyincreased viral load but also caused more severe side effects overall.For some of the patients with CD4 counts lower than 100, theincreases in viral burden were sustained. The study's authors notedthat this phenomenon caused "no obvious detrimental effects."

According to Chiron spokesman Larry Kurtz, the Emeryville, Calif.-based company has expanded its product development budget for IL-2 based on its apparent potential as an AIDS drug. "It's a cornerstoneproduct in our Chiron Therapeutics business," Kurtz told BioWorld.

However, Kurtz cautioned that the NIAID study was small and itsresults need to be reproduced. "We are excited but we don't want tobe premature in making claims for this product," he said. Chironcurrently has several Phase I/II studies under way testing variousdoses, regimens and formulations of IL-2 in HIV-infected patients.

Chiron is the only manufacturer of IL-2 with an approved indication(as a treatment for kidney cancer) and, if results are positive, wouldfile the regulatory submission to gain approval of the drug as anAIDS therapy. The NIH has applied for a patent on the indication andregimen described in the Journal study. If that regimen proves themost effective, Chiron might potentially pay a royalty to the NIH. n

-- Lisa Piercey Washington Editor

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