FDAnews
www.fdanews.com/articles/89838-ym-ends-trial-of-tesmilifene-in-advanced-breast-cancer

YM ENDS TRIAL OF TESMILIFENE IN ADVANCED BREAST CANCER

January 31, 2007

YM BioSciences announced that the independent data safety monitoring board (DSMB) for the pivotal Phase III trial of tesmilifene in patients with metastatic or recurrent breast cancer has completed its third planned safety and efficacy analysis. The DSMB advised the company to stop the trial based on an interim analysis of 351 events, indicating it is very unlikely significant differences in overall survival will be shown between treatment arms as the data mature. The trial was not stopped due to safety concerns relating to the product.

"We are very disappointed by this outcome and will be evaluating the data to understand why tesmilifene did not add a clinical benefit in this trial," David Allan, chairman and CEO of YM BioSciences, said.

The trial compared the survival of patients treated with tesmilifene combined with epirubicin/cyclophosphamide to the survival of those treated with epirubicin/cyclophosphamide alone among women with rapidly progressing metastatic and/or recurrent breast cancer. The study, which completed enrollment of 723 patients in September 2005, was the subject of a special protocol assessment and fast-track designation for advanced breast cancer from the FDA.

The trial was conducted according to a sequential design that permitted a number of planned interim analyses while the trial continued until one of two specific statistical conditions was satisfied. At each analysis, survival for the tesmilifene-containing treatment arm and the control arm was calculated and then reviewed by the DSMB. The trial was to be concluded if either the tesmilifene-containing treatment arm was superior to the control by a specified margin or it was determined that such evidence was not going to be found. After the third planned analysis, the DSMB concluded that the trial was highly unlikely to achieve a prespecified survival benefit.

Tesmilifene selectively targets multidrug-resistant tumor cells, sensitizing them to chemotherapy. Tesmilifene may offer clinical benefit in a number of tumor types and is being tested with a variety of chemotherapeutic regimens. In addition to this trial, a Phase III trial of tesmilifene with doxorubicin in metastatic or recurrent breast cancer has been completed and a Phase II study to evaluate tesmilifene plus docetaxel in patients with metastatic breast cancer is being conducted in collaboration with sanofi-aventis.