A modified form of the enzyme L-asparaginase, Enzon Inc.'sPEG-L-asparaginase (trade-named Oncaspar), seems toincrease its effectiveness in treating acute lymphoblasticleukemia (ALL), according to results presented last week inHouston at an international conference on leukemia sponsoredby the University of Texas M.D. Anderson Cancer Center.
L-asparaginase, which inhibits the synthesis of the amino acidasparagine, has already been shown to be efficacious intreating ALL because leukemic cells absolutely requireasparagine to grow. But the currently available form of thedrug causes allergic reactions; 78 percent of treated patientsdevelop dose-limiting hypersensitivity reactions, even to thepoint of anaphylaxis.
As well, according to results presented by Joanne Kurtzberg ofDuke University, large numbers of patients develop "silenthypersensitivity reactions." They produce anti-asparaginaseantibodies that reduce the efficacy of long-term or repeatedtreatment regimens.
But Kurtzberg found that polyethylene glycol (PEG)-conjugatedasparaginase exhibits an increased serum half-life and is lessimmunogenic than the unmodified enzyme. "In newly diagnosedpatients who have never been exposed to asparaginase, thehalf-life of the PEG conjugated enzyme is six to tenfoldgreater than that of the native enzyme preparations," she said.
Kurtzberg also determined that "most patients hypersensitiveto the native enzyme will tolerate PEG-asparaginase withoutfurther clinical hypersensitivity."
And Michael Keating, who participated in the Phase I/II trialson PEG-asparaginase at M.D. Anderson, reported that the serumhalf-life of PEG-asparaginase in 37 patients who hadpreviously been treated with the native form of the enzymewas 357 hours, as compared with the 20-hour half-life of thenative enzyme.
Keating also found that "65 to 75 percent of patients with ahistory of allergic reactions to native L-asparaginase canreceive PEG-asparaginase with no untoward side effects."Keating also reported that in these trials, one patient with ALLand two patients with lymphoma had complete remissionsfollowing PEG-asparaginase therapy. Enzon of South Plainfield,N.J., filed a product license application (PLA) on PEG-L-asparaginase in January 1991.
Enzon's stock (NASDAQ:ENZN) closed Monday at $4.25 a share,up 13 cents.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.