By Lisa Seachrist

Washington Editor

WASHINGTON — The FDA has approved the first humanized antibody for the prevention of acute graft rejection in kidney transplant recipients.

Late Wednesday evening, the agency granted Hoffman-La Roche Inc., of Nutley, N.J., and Basel, Switzerland, marketing clearance for Zenapax (daclizumab) as a prophylactic for acute organ rejection in patients receiving renal transplants. Roche licensed the rights to Zenapax from Protein Design Labs Inc., of Mountain View, Calif., and PDL will receive royalties from any sales.

Diane Donlon, a spokesperson for Roche, noted that "the transplant community is anxious to get the drug," and Roche intends to start shipping Zenapax within the week. The price for a course of treatment will be $6,800.

"We are pretty excited," said Jon Saxe, president of PDL. "Not only is this our first drug approved, it is the first of a new class of drugs to be approved."

In approving the drug, the FDA followed the advice of its Biological Response Modifiers Advisory Committee, which voted 12-0 in October to recommend Zenapax for marketing. Zenapax is an intravenous formulation that is given just prior to transplant surgery and four times afterward at two week intervals.

The agency based its approval on two pivotal clinical trials that showed when Zenapax was added to standard immunosuppressive regimens used for patients undergoing kidney transplantation, those patients receiving Zenapax had fewer rejection episodes.

In one trial, Zenapax reduced the incidence of rejection episodes from 47 percent to 27 percent, and in the second from 35 percent to 22 percent. One trial also showed that Zenapax increased survival in the year after surgery.

Reducing Rejection Increases Kidney Supply

In 1996, 12,000 people in the United States received a kidney transplant. Approximately 35,000 were on the waiting list and 1,800 of those people died waiting for a kidney to become available.

"Stopping rejection episodes is significant for the kidney transplant community," Saxe said. "If you can cut down on the number of rejection episodes you can cut down on the need for second and third kidney transplants, meaning that kidney transplantation would be available to more people."

Unlike other immunosuppressive drugs that trigger a generalized immunosuppression, Zenapax works by targeting activated T cells, white blood cells programmed to attack foreign substances. Zenapax simply prevents the T cells from binding to the new kidney and harming it. As a result, Zenapax doesn't increase the risk for immune-based cancers and infections associated with other transplant drugs.

Zenapax has few side effects, and the major concern for monoclonal antibodies — that the patient will develop allergic responses — was solved by the fact that PDL designed the drug to have mostly human components.

In a written statement, Michael Friedman, lead deputy commissioner of the FDA, said, "This new biotech product gives transplant patients and their doctors a new, important weapon to fight kidney rejection. Adding daclizumab to other standard immunosuppressive treatments can be very beneficial for patients, with no evidence of additional serious side effects."

Roche also is exploring whether Zenapax in combination with prednisone and its own antirejection drug, CellCept, can prevent rejection well enough to obviate the need for cyclosporine — currently the standard of care for transplantation.

In addition, Roche has clinical trials of Zenapax in psoriasis, uveitis (a sight-threatening autoimmune disease) and tropical spastic paraparesis (a clinical model of multiple sclerosis). Zenapax also is being studied in blood cancers and liver transplantation.

Saxe noted transplant surgeons already are expressing interest in Zenapax for all organ transplants.

PDL's stock (NASDAQ: PDLI) closed Thursday at $36.25, down $2.875. *