By Lisa Seachrist

Washington Editor

Maxim Pharmaceuticals Inc.'s Phase III study testing Maxamine (histamine dihydrochloride) in combination with interleukin-2 (IL-2) showed the combination therapy significantly improved survival in patients with Stage IV melanoma.

Maxamine plus IL-2 improved survival for all groups of patients with end-stage melanoma; however, the survival benefit was greatest in patients with melanoma metastases to the liver. In addition to proving a survival benefit, the company said a preliminary analysis of the data indicates the therapy provides substantial quality-of-life benefits.

Maxim intends to use this data to file an NDA for the drug this summer.

"We are very, very pleased with the outcome of this trial," said Larry Stambaugh, chairman and CEO of San Diego-based Maxim. "This is a very important milestone for patients who haven't had any other option. This is the first study in melanoma to show a survival benefit."

Th study included 305 patients with advanced Stage IV melanoma. Melanoma is the most deadly and serious form of skin cancer and is one of the most rapidly increasing cancers in the world. Because there is no effective treatment for advanced Stage IV melanoma, Maxamine has been granted priority review status at FDA.

The Phase III trial pitted Maxamine and IL-2 against IL-2 alone, which is already approved for advanced stage melanoma. While the trial was a randomized multi-center Phase III study, it wasn't blinded because patients on Maxamine all have a very noticeable flushing reaction.

Patients injected themselves each morning and each evening with Maxamine plus IL-2 (in separate syringes) or IL-2 alone. Patients treated with Maxamine plus IL-2 had a median survival of 326 days compared to 251 days for patients treated with only IL-2.

For patients with liver metastases, the survival advantage with Maxamine was even more dramatic. For those patients, Maxamine/IL-2 yielded a median survival of 363 days compared to 157 days for the IL-2 control patients.

"Even more important, the analysis of the survival curves show Maxamine provided a significant advantage," said Kurt Gehlsen, Maxim's vice president of development and chief technical officer. "Patients also did significantly better on the secondary endpoint of quality of life, which is really icing on the cake for us."

Gehlsen noted the quality-of-life endpoint was significant because patients were injecting themselves, and IL-2 is known to cause flu-like symptoms. Maxamine, in addition to causing a flushing reaction as a result of minor vasodilation, knocks out tumor necrosis factor and interleukin-1 - the two cytokines produced in response to IL-2 that appear to be responsible for the flu-like reaction, Gehlsen said.

"We've actually had patients say they enjoy the flushing reaction because they know the drug is working," Gehlsen said. "We also had no problem with people complying with the protocol. The self-injection wasn't a problem."

Other secondary endpoints included safety and time to disease progression. The disease-progression endpoint has historically been the primary endpoint for many oncology trials and the basis for FDA approval, Stambaugh said.

"What's important is we increased patient survival without adding additional toxicity," he said. "Not only that, patients also have an improved quality of life."

Maxamine is a histamine type-2 receptor agonist, a potent molecule that shuts off production of free radicals, thereby protecting T cells and natural killer cells. Maxamine Therapy combines Maxamine with various immuno-stimulatory cytokines such as IL-2 and interferon-alpha. The therapy is based on the discovery of a universal mechanism that suppresses the capacity of the immune system to detect and destroy tumor cells. Maxamine therapy resolves that immune suppression.

In addition to melanoma, Maxim is conducting a Phase III study of Maxamine in acute myelogenous leukemia. The company has Phase II studies under way of Maxamine in hepatitis C and advanced renal cell carcinoma. In addition, Stambaugh said, the company is considering expanding testing of Maxamine into prostate, lung, breast, colon or other cancers where immunosuppression is a problem.

Maxim is also developing MaxVax, a mucosal vaccine carrier platform, and MaxDerm, for the treatment of oral mucositis, herpes, decubitus ulcers, shingles, burns and related conditions.

Maxim's stock (NASDAQ:MAXM) closed Tuesday at $38.625, down $2.125.

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