By Lisa Seachrist

Washington Editor

Maxim Pharmaceuticals Inc. initiated a multi-center, international Phase III clinical trial of its lead cancer treatment, Maxamine Therapy, to prevent relapses in acute myelogenous leukemia (AML) the most common form of leukemia in adults.

Maxamine Therapy — an at-home immunomodulatory therapy — is currently in two Phase III trials as a cancer therapy for advanced malignant melanoma. Those studies are expected to be completed in 1999.

"Conducting three Phase III clinical trials of Maxamine in two different diseases increases the likelihood of success," said Larry Stambaugh, president and CEO of the San Diego company. "Success in any one of these trials should support a marketing application."

Maxamine Therapy is a combination of Maxamine, a histamine type-2 receptor agonist and the stimulating cytokine interleukin 2 (IL-2), which is provided by Chiron Corp., of Emeryville, Calif., for the trials. The drug combination is designed to augment and protect the natural immune response the body has to certain cancers.

In many tumors, monocytes — immune cells vital in combating bacterial infections but of little utility in fighting cancer — invade the tumor and release free oxygen species in an attempt to kill the cancer cells in the same way they kill bacteria. That strategy, however, triggers cancer-fighting natural killer (NK) cells to die via programmed cell death.

Maxamine, like naturally produced histamine, inhibits the production of free radicals, allowing NK cells to invade the tumor. The cytokines stimulate the production of both NK cells and cancer-fighting T cells for more effective tumor fighting.

"There is no evolutionary pressure on the immune system to develop a means to fight cancer because it happens so late in life," said Kurt Gehlsen, vice president of development and chief technical officer at Maxim. "As a result, we end up with inappropriate cells fighting the cancer. Maxamine Therapy redirects the immune response to use the correct cells."

In AML, prospects for long-term survival are poor. Once diagnosed, patients are typically treated with chemotherapy. While the majority of the patients achieve a complete remission, 75 to 85 percent will relapse within a year. Even if the disease remits once more, less than five percent of patients who have relapsed will survive long term. Preventing relapse is the most important element in long-term survival.

Phase II Data Encouraging

Phase II studies indicate that a course of Maxamine Therapy, given after the first remission is achieved, can prolong the time to relapse from an average of 12 months to in excess of 26 months — the study has not yet reached a median time to relapse.

In the Phase III trial, the company will study 200 patients who have achieved their first remission. Half of them will receive Maxamine Therapy and the other half will receive no treatment, which is the current standard of care. The trial also will include 100 patients who had a relapse and achieved their second remission. Active arm patients will inject themselves with Maxamine Therapy twice a day for 21 days with a 21 day rest before starting another cycle of injections for 4 cycles. After that, patients will take two injections a day for 21 days with a six-week rest between cycles, resulting in a total of 10 cycles of treatment.

"Establishing remission and preventing relapse is vital in AML," Gehlsen said. "Because Maxamine Therapy is an outpatient treatment, patients can have a good quality of life while they attempt to prevent relapse."

In the melanoma studies, which focus on patients with very advanced disease rather than patients experiencing remission, Stambaugh noted that the quality of life was particularly important for patients who would otherwise have to endure extensive chemotherapy treatments.

In addition to melanoma and AML, the company is exploring Maxamine Therapy as a treatment for a number of cancers that trigger an immune response, including prostate cancer, renal cell carcinoma, multiple myeloma and breast cancer. The company also will begin a Phase II study of Maxamine Therapy for the treatment of hepatitis C this spring.

"Overall, we hope this is a very important step for both the utilization of immune therapy, which hasn't been as effective as many have hoped, and the development of rational ways to approach cancer," Gehlsen said.

Maxim's stock (AMEX:MMP) closed Thursday at $16, up $0.375. *