Maxim Pharmaceuticals to withdraw NDA for advanced malignant melanoma

Nov 2 2004

Maxim Pharmaceuticals has announced that based upon the negative outcome of it's confirmatory Phase 3 clinical trial (M0104) studying Ceplene(TM) (histamine dihydrochloride) in combination with Interleukin-2 (IL-2) in advanced malignant melanoma patients with liver metastases, it plans to close the treatment protocol approved by the FDA earlier this year.

The treatment protocol allowed Maxim to provide expanded access of Ceplene therapy to advanced malignant melanoma patients while investigation of the drug continued in the confirmatory M0104 clinical trial. Any patient currently enrolled in the treatment protocol will be allowed to complete their treatment regimen under a compassionate use program. Maxim also intends to withdraw its pending U.S. New Drug Application seeking approval of Ceplene therapy to treat advanced malignant melanoma patients with liver metastases.

Maxim Pharmaceuticals also reported today at the 29th European Society for Medical Oncology Congress in Vienna, Austria, data from the Phase 3 M0104 clinical trial studying Ceplene in combination with IL-2 for the treatment of advanced malignant melanoma patients with liver metastases. The Company previously reported that the trial did not meet its primary endpoint. The combination therapy was generally well tolerated, and safety was consistent with previous clinical experience.

"Our continuing evaluation of the M0104 trial and the previous Phase 3 study has noted differences, including fewer patients entering cycles 3, 4 and 5 in the M0104 study, and more patients receiving dose reductions in the combination arm compared to previous experience. Although we will continue to try and learn from the melanoma results, our focus has shifted to potential filings for marketing authorization in acute myeloid leukemia based on our positive Phase 3 trial reported this summer, as well as partnering efforts for both Ceplene and our apoptosis compounds."

The M0104 study was conducted under the Special Protocol Assessment procedure of the FDA to confirm results from an earlier Phase 3 trial (M01), which demonstrated statistical significance at 12 months in the subgroup of advanced malignant melanoma patients with liver metastases. The completed M0104 trial was a multi-center, randomized, and controlled Phase 3 study evaluating Ceplene plus IL-2 against IL-2 alone in 230 patients at 35 sites in North America and Europe. IL-2 is an immunotherapeutic agent approved in the U.S., at significantly higher doses than used in M0104, for the treatment of advanced malignant melanoma. The M0104 trial was conducted under the same treatment protocol as the prior M01 study, but enrollment was limited to advanced malignant melanoma patients with liver metastases. The primary endpoint of the trial was duration of patient survival, as assessed by the stratified log-rank test in the intent-to-treat population.