Genetics Institute Corp. officials are investigating the cause ofadverse events that hospitalized 12 of 17 advanced kidney cancerpatients being treated with interleukin-12 in a Phase II trial. One ofthose patients died Friday, a day after the company suspended thetrial.

"To determine what caused the adverse events is the company'shighest priority," said Dennis Harp, Genetics Institute's manager,public policy and communications. "It may take us some time to getan answer but we're committed to understanding exactly what hasgone on."

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The Cambridge, Mass. company said it expects to return to a dose-escalating Phase I study with the new dosage form after it determinesthe cause of the adverse events. Genetics Institute changed the dosingschedule and dosage form when it went into Phase II.

The recombinant human interleukin-12 (rhIL-12) product is beingdeveloped with American Home Products Corp.'s Wyeth-AyerstLaboratories pharmaceutical division. American Home Productsowns 64 percent of Genetics Institute's 26 million outstanding shares,and has a call option to purchase the rest of Genetics Institute at anescalating price: it is $73.95 per share now, and rises to $85 inDecember 1996, when the option expires.

"That's why the stock is only off a dollar," David Stone, a managingdirector in Cowen & Co.'s Boston office, said early Monday. Thestock (NASDAQ:GENIZ) closed Monday at $34.53, down $1.47, or4 percent.

IL-12, an early stage product, doesn't even appear in Cowen & Co.'searnings model, said Stone, whose company maintained a buy ratingon the stock. "Our sense of their value as an investment is keyedprimarily to the American Home Products call option of $85 inDecember 1996," he said.

Harp said the five patients who had been treated but not hospitalizedhave been notified, and are being monitored by their physicians.Genetics Institute still was investigating potential causes of theadverse events, and would not comment about the doses that wereused, how much drug was received by the patients, and individualpatient information.

The study design called for multiple doses of the same dosage to begiven over several days, Harp said. The Phase II study started in lateMay.

Hoffmann-La Roche Inc., of Nutley, N.J., also is developing IL-12,and has the protein in a Phase I trial for the same kidney cancerindication. The companies had collaborated on preclinicaldevelopment of IL-12, and later agreed to a cross-licensingarrangement. A Hoffmann-La Roche spokeswoman said itsdevelopment plans are unaffected by the Genetics Institute setback.

Yamanouchi Pharmaceutical Co. Ltd., of Tokyo, is in a joint venturewith Genetics Institute for development of three proteins, includingIL-12 in Japan. Yamanouchi has not started trials in Japan, Harp said.n

-- Jim Shrine

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