Protein Design Labs Inc.'s (PDL) humanized antibody fortreating relapsed acute myeloid leukemia has caused noimmune response in eight patients evaluated in a Phase I trial,the company announced.

David Scheinberg, chief of the leukemia service at New York'sMemorial Sloan Kettering Cancer Center reported on the PhaseI results at an international conference on leukemia sponsoredby the University of Texas M.D. Anderson Cancer Center inHouston. Twelve patients with relapsed acute myeloidleukemia (AML) received multiple doses of PDL's humanizedSmart M195 antibody in the Phase I trial; four of those patientsare still being evaluated. The study involved one of four dosesof antibody -- 0.5, 1.0, 3.0, and 10.0 milligrams per squaremeter -- administered six times over a three-week period.

They were monitored for HAMA antibody titers for up to 16weeks (but for at least three weeks) after the final treatment.As well, the antibody rapidly localized to the disease sites, andthe side effects observed in three patients -- fever, chills andshortness of breath--were infusion-related and eitherspontaneously disappeared or could be reversed withantihistamine, Scheinberg said.

Scheinberg also reported the preliminary results of twoongoing Phase II trials of the wholly mouse M195 antibodylabeled with radioactive iodine to treat relapsed patients withacute promyelocytic leukemia and for treating relapsed AMLpatients prior to bone marrow transplant.

All the above trials have been under physician-sponsoredinvestigational new drug (IND) applications, said PeterDworkin, PDL's director of corporate communication. Theantibody they use was developed by Sloan-Kettering'sScheinberg, Dworkin told BioWorld. For a company-sponsoredIND, "the material would come from our Minneapolismanufacturing facility," Dworkin said.

PDL (NASDAQ:PDLI) of Mountain View, Calif. has usedcomputerized design methods to create its 90-percent-humanM195 antibody. Only the antigen-binding site contains mousesequences.

Clinical safety studies of another of PDL's humanized antibody-- an anti-Tac antibody for treating graft-vs.-host disease,organ transplant rejection and certain autoimmune diseases --also demonstrated that patients don't have an immune reactionto the mouse portion of the antibody molecule. In those Phase Itrials, the results of which were reported in December, thepatients received a single dose of antibody, escalated from 0.5to 1.5 milligrams per kilogram per patients over two hours. ThePhase Is on M195 "are one of the first multi-dose trials on afully humanized antibody in the U.S.," Dworkin told BioWorld.

-- Jennifer Van Brunt Senior Editor

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