By Frances Bishopp

After Phase II clinical trial results demonstrated that its lead product, Maxamine, doubled survival time for patients with advanced-stage malignant melanoma, Maxim Pharmaceuticals Inc. has begun Phase III clinical trials in the U.S.

Maxamine is being developed by the San Diego-based company as an adjuvant to cytokine therapy for the treatment of cancer and infectious diseases. The technology, which originally came from Sweden, involves more effective stimulation of the appropriate immune cell systems that are capable of destroying tumor cells.

Maxamine, a dihydrochloride salt form of histamine, blocks the production of reactive oxygen metabolites by phagocytes present within the tumor tissue and thereby prevents the down regulation of natural killer cells and T cells.

This down regulation is of sufficient potency to block much of the stimulatory effects of interleukin-2 (IL-2) and alpha interferon. By administering Maxamine concurrently with IL-2 or alpha interferon, the immune stimulatory effects of these cytokines are protected and enhanced.

The Phase III clinical trial will enroll 200 patients and will have two arms with 100 patients in each. One arm will be treated with a coadministration of Maxamine and IL-2.

Patients in the other arm, the control group, will be treated with IL-2 alone. The primary endpoint of the study is overall patient survival, and the secondary endpoints include time to progression, tumor response, duration of response and quality of life.

The study will be conducted at more than 15 locations throughout the U.S.

Larry Stambough, chairman, president and CEO of Maxim, told BioWorld Today that Maxim will also be initiating two other Phase III clinical trials for Maxamine later this year: Maxamine for melanoma in Australia and Maxamine for acute myelogenous leukemia in Europe.

The Australian study's control arm will receive DTIC, a common chemotherapy agent. The European study's control arm for acute myelogenous leukemia will receive IL-2. This study, Stambough said, has potential sites in the U.S. as well.

The recently reported Phase II trial results of Maxamine for melanoma in combination with IL-2 or alpha interferon in late-stage patients demonstrated survival duration of more than 15 months, compared to a mean of seven months with existing treatments, Stambough said.

What is being proved is that IL-2 and Maxamine combined is better than chemotherapy, Stambough said. Maxamine is synergistic with the cytokine therapy and is able to protect natural killer cells and T cells that are effective against cancer, Stambough explained.

"By protecting these cells, we have been able to lower the dose of cytokine therapy so there is less toxicity. These patients are treating themselves on an outpatient basis and we are seeing substantially improved efficacy in survival," Stambough said.

Maxim owns worldwide exclusive rights to the Maxamine technology. The company's second platform technology, MaxVax, uses a mucosal vaccine carrier/adjuvant for a broad range of infectious diseases.

Maxim's current cash on hand is $15 million. Maxim's stock (AMEX:MMP) closed Thursday at $9.25, up 19 cents. *