Published results suggest Maxim Pharmaceuticals' EpiLeukincombination therapy effectively extended remission duration in acutemyelogenous leukemia patients when compared to interleukin-2 (IL-2) alone or other standard treatments.

EpiLeukin is a technology combining an H2 receptor agonist, orhistamine, with the cytokines IL-2 and/or alpha interferon. Thehistamine helps potentiate the natural killer (NK) cell activity ofcytokines, the company said.

"There is an inverse relationship that exists in which with higher ornormal levels of histamine, one has a relatively lower likelihood ofacquiring cancer in the first place and a relatively lower likelihood ofgetting malignancies from the cancers they have," Dannie King,president and chief operating officer of San Diego-based Maxim, toldBioWorld Today.

IL-2 is known to activate the anti-tumor cytotoxicity of humannatural killer cells preclinically, but that mechanism has not carriedover to studies in human tumors, King said. He said a previouslyunknown effect of phagocytes _ their down-regulation of NK cells_ is reversed by this therapy, he said, adding that release ofhistamine helps keep the NK activity at high levels.

Results from a small Phase II study involving 12 acute myelogenousleukemia (AML) patients showed nine remained in completeremission at 12 to 34 months. Maxim said it is averaging remission ofmore than 18 months, while assessment of earlier AML patients inthe same institutions showed a median time to first remission of 13months and six months to second remission.

The interim results from the Phase II AML study were reportedThursday in the British Journal of Haemotology March 1, 1996,issue.

Results of a EpiLeukin study in metastatic malignant melanoma werepublished in 1994. It involved 16 patients, nine of whom were givenhistamine in combination with IL-2 and alpha interferon. Four ofeight evaluable drug-treated patients had partial responses, while twoothers showed regression at one site of metastasis. In the seven whodid not receive histamine only one partial response was seen.

EpiLeukin also is being tested in Phase II studies in Sweden in renalcell carcinoma and multiple myeloma. King said Maxim is workingon protocols for an international, pivotal study of the combinationtherapy that would support registration in Europe and the U.S.

Maxim was founded in 1993 and is based on the EpiLeukintechnology and work in mucosal vaccines, both of which werelicensed from Swedish scientists.

"The results of the AML and malignant melanoma studiesdemonstrate that our small molecule immune modulator technologyenhances the anti-tumor potential of IL-2 in humans, indicating thatcytokines, when used in combination with an H2 receptor agonist,may be a safe and effective approach to immunotherapy meritingfurther investigation," said Larry Stambaugh, Maxim's chairman andCEO. "In addition, EpiLeukin is designed to offer several compellingpharmacoeconomic benefits, including outpatient therapy, improvedclinical efficacy, higher levels of safety, reduced treatment cost andimproved patient compliance." n

-- Jim Shrine

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