Adventrx Pharmaceuticals' folate-based biomodulator CoFactor failed to demonstrate a safety advantage over leucovorin in combination with 5-fluorouracil in patients with metastatic colorectal cancer, Adventrx CEO Evan Levine told investors during an Oct. 1 conference call.

In the European Phase IIb study, "we were looking for a reduction in the proportion of patients with at least one grade 3 or greater hematological or gastrointestinal adverse event. The study demonstrated no statistically significant differences between the arms and overall safety and efficacy variables using the infusional method" of dosing the 5-FU, Levine said.

Both U.S. studies of the CoFactor/5-FU combination employ bolus administration of 5-FU, Levine explained, suggesting that the method of administration could make a difference in the outcomes of those studies.

"If you look at the two arms, when you start to take away the side effects that are related directly to disease, you don't see a real difference here in the safety, and it's low. I've always said it's lower with infusional than bolus, and we are very hopeful that that difference will point to something, but that is going to take further analysis," Levine said.

Meanwhile, the exec said the firm will focus on its regulatory program for emulsion formulations of vinorelbine (ANX-530) and docetaxel (ANX-514) for the rest of 2007. Adventrx anticipates announcing results from a bioequivalence study of ANX-530 later this quarter and filing an NDA next year under the 505(b)(2) mechanism.

Adventrx designed CoFactor to replace leucovorin, the currently preferred adjuvant, as a method to enhance the activity and reduce associated toxicity of the widely used chemotherapeutic agent 5-FU.

A U.S. Phase II study of the CoFactor/5-FU combination in advanced breast cancer in on track to complete accrual this year, with data available early in the second quarter of 2008, Levine said.

However, the future of a newly announced Phase III trial in metastatic colorectal cancer could depend on further analysis of the European data. The San Diego firm announced in August that FDA had awarded CoFactor fast track status in the colorectal cancer indication (¹ Also see "Adventrx CoFactor Gets FDA Fast Track Designation For Colorectal Cancer" - Pink Sheet, 16 August, 2007.).

Levine said Adventrx would meet with the study's data safety monitoring board and go over the data with outside parties with which the firm is "involved in some late-stage partnership situations" before giving guidance on how it is going to proceed with the Phase III trial.

"We think that the method of administration of 5-FU is an important consideration," Adventrx Chief Medical Officer James Merritt said. "We think there is considerable scientific data that support that leucovorin has more of an impact on the bolus administration, or intermittent administration, of 5-FU than any kind of continuous infusion, and if that is true and CoFactor is superior to leucovorin, then those intermittent bolus regimens do offer a much better setting to disclose the benefit."

-Shirley Haley (s.haley@elsevier.com)

Adventrx Turns Focus From CoFactor To Vinorelbine, Docetaxel After Phase IIb Failure In CRC

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