Washington Editor

Maxim Pharmaceuticals Inc. is looking for a life preserver.

The San Diego company conceded that another Phase III trial of Ceplene (histamine dihydrochloride) is needed before it seeks FDA approval of the product. The decision was based on ongoing correspondence with the agency, as well as consultations with external advisers, both of which determined that the additional study of Ceplene combined with interleukin-2 for acute myeloid leukemia patients in complete remission would be necessary before applying for marketing clearance in the U.S.

"We believed another study was a possibility," Maxim Chairman and CEO Larry Stambaugh said. "It's hard to predict regulatory outcomes these days, but right now they generally seem to be conservative, so that was among the possibilities."

As a sign of fiscal concern at Maxim, the company allowed that the cost of conducting another trial would force it to seek a partner. It had $52.9 million in cash, cash equivalents and investments as of Sept. 30, the end of its fiscal year, and burned through $41.1 million in the preceding 12 months. As a result, Maxim intends to pursue a collaboration deal in the U.S.

"We have ongoing discussions with companies about being partners on Ceplene's development," Stambaugh said. "It's pretty hard to lay out partnering timelines. Those things have a life of discussion, and after you reach an agreement, there is some time to [complete] it."

He declined to predict the impact a breakdown in partnering talks could have on the program's development. Maxim holds all rights to the product.

The company, which is continuing discussions with the FDA regarding trial design, also said it is carrying on discussions with European regulators to determine if an additional Phase III trial is necessary for approval in that territory.

"We don't know what the next trial design would be," Stambaugh said, "until we complete discussions with the regulators."

Any upcoming trial would follow a previously completed Phase III study, which met its primary endpoint, a measure of improvement in leukemia-free survival (p=0.0096). It tested the drug and IL-2 in 320 patients at a number of sites in Europe, North America, Israel, New Zealand and Australia. Resulting data cover three years, made up of 18 months of patient treatment and another 18 months of follow-up. The news boosted the company's stock value to $8.70 on the day it was released. (See BioWorld Today, May 13, 2004.)

The new study also would follow negative Phase III findings from a confirmatory trial of Ceplene and IL-2 in advanced malignant melanoma patients, which failed to demonstrate an improvement in overall patient survival. After unveiling the results in September, Maxim withdrew its melanoma application from the FDA, planned to remove a European application and said it no longer would pursue that indication. It first filed a new drug application for advanced malignant melanoma in 2000. The damaging data, which dropped the company's stock by nearly 50 percent the day the news came out, left shares at $3.04. Soon after, Maxim laid off of nearly half its work force in order to slow cash consumption. (See BioWorld Today, Sept. 21, 2004, and Oct. 19, 2004.)

The drug is designed to maintain the integrity of immune cells, particularly T cells and natural killer cells, in cancer patients. The treatment aims to facilitate immune-mediated destruction of cancer cells, including leukemic cells, and also to improve the efficiency of T-cell and natural killer-cell-activating agents such as IL-2.

The company also is studying Ceplene in Phase II trials in patients with hepatitis C and advanced renal-cell carcinoma. Stambaugh said the studies would conclude soon, with results expected to be reported in the first half of this year. He added that Maxim subsequently would evaluate how to carry forward with such programs.

On Tuesday, its stock (NASDAQ:MAXM) dropped 16 cents to close at $2.51.