YM BioSciences Inc. said it reached agreement with the FDA for a Phase III registration trial of its lead drug, tesmilifene, for advanced metastatic or recurrent breast cancer.

The study is designed to compare the overall survival times of tesmilifene in combination with the anthracycline epirubicin and cyclophosphamide vs. epirubicin/cyclophosphamide alone. Tesmilifene is designed to enhance the chemotherapeutic effects of anthracyclines and taxanes.

The trial design was signed off by the agency under its special protocol assessment program, a process launched last May and designed to put the FDA in agreement with a trial sponsor to ensure the approvability of a protocol.

"This provides us an absolutely clear path to market for that drug," David Allan, Mississauga, Ontario-based YM's chairman and CEO, told BioWorld Today. "Now that we have negotiated what this trial has to show, our probability of hitting the endpoints we have worked out with the FDA is pretty high because they are significantly lower than the endpoints we achieved in the first Phase III. It looks to us like this drug is going to market."

He said the FDA is requiring the small molecule to show half the effectiveness it demonstrated in the prior Phase III study in advanced metastatic breast cancer. That international trial, conducted by the National Cancer Institute of Canada, compared the combination of tesmilifene and doxorubicin, another anthracycline, vs. doxorubicin alone. Investigators found that patients receiving the combination therapy had greater than 50 percent median survival improvement over patients receiving doxorubicin alone (23.6 months vs. 15.6 months).

"We are hoping to show tesmilifene's effectiveness with the current market leader, epirubicin, rather than doxorubicin," David Harper, YM's director of licensing and business development, told BioWorld Today.

YM, which reported C$10.4 million (US$7 million) in cash and short-term investments for the period ended Dec. 31, expects a partner to move tesmilifene forward in the coming trial, scheduled to begin later this year. Allan added that the use of the second-generation drug regimen in the comparative arm also sends a good signal to potential partners.

"We think a partnership will probably happen, given that we have now completed the negotiation on the parameters for and the endpoints of the registration trial," Allan said. "A year ago the FDA told us that the first Phase III would count as one of two well-controlled trials for registration."

He said survival remains the upcoming trial's primary endpoint, but declined to specify further endpoints. Allan said it would enroll more than the 305 patients recruited in the first Phase III study.

Though tesmilifene's mechanism of action remains unknown, Allan said it works intracellularly to help retain chemotherapeutic effects in a cell for a longer period of time than they would otherwise. According to Allan, Phase II data of the drug's effect on taxanes support its eventual registration to be used in combination with that class of drugs as well.

In addition to tesmilifene, YM is developing TheraCIM h-R3, an epidermal growth factor receptor humanized monoclonal antibody. It recently completed enrollment of a Phase II trial in head and neck cancers. YM also has Norelin, a gonadotropin-releasing hormone cancer vaccine that also recently completed enrollment in a Phase I/II trial for hormone-dependent prostate cancer.

YM's stock (TSX:YM.PR.B) closed unchanged Tuesday at C$1.50.