West Coast Editor

About two weeks after pulling down $32 million to fund its Phase III trial with the sulfonylhydrazine alkylating agent cloretazine in acute myelogenous leukemia, Vion Pharmaceuticals Inc. has reached agreement with the FDA on a special protocol assessment.

The company's stock (NASDAQ:VION) closed Thursday at $3.29, up 1 cent. Officials at the firm could not be reached.

The trial is expected to start this quarter and accrue for more than 30 months at centers in North America and Europe. Placebo controlled, randomized and double blinded, it's designed to enroll 420 patients with acute myelogenous leukemia (AML) in first relapse, having gained complete remission (CR) of at least three months but not longer than 24.

Patients will be randomized at a ratio of 2 to 1 in the experimental arm to the control arm, and stratified according to their age and the length of first CR. The primary endpoint is the objective response rate, defined as CR plus CRp - that is, a complete remission with incomplete recovery of platelet count.

Designed to show a 50 percent difference in the objective response rate between the experimental arm and the control arm, the study has secondary endpoints that include time to progression, duration of response, survival and toxicity. An interim analysis is planned after accrual and follow up for the objective response rate of the first 210 patients.

An alkylating agent for leukemia recently made news as part of the buyout by Fremont, Calif.-based Protein Design Labs Inc. of ESP Pharma Inc., of Edison, N.J., for $300 million in cash and about $175 million in stock. (See BioWorld Today, Jan. 26, 2005.)

That drug is ESP's approved Busulfex, a formulation of busulfan for a different type of leukemia - chronic myelogenous - to be used in combination with cyclophosphamide as a conditioning regimen before allogeneic hematopoietic progenitor-cell transplant.

AML has thwarted other worthy challengers. Cambridge, Mass.-based Genzyme Corp.'s clofarabine, a next-generation purine nucleoside analogue brand named Clolar, won FDA approval late last year for pediatric refractory or relapsed acute lymphoblastic leukemia, but the agency's advisory panel turned thumbs-down on the drug for AML. (See BioWorld Today, Dec. 30, 2004.)

For Vion's cloretazine Phase III, the SPA doesn't provide any guarantee of approval, but offers official evaluation and guidance from the FDA on proposed protocols to minimize nasty surprises later.

Also in Phase II, Vion has Triapine, an inhibitor of DNA synthesis, combined with gemcitabine, for pancreatic cancer and non-small-cell lung cancer. The drug targets ribonucleotide reductase, like Toronto-based Lorus Therapeutics Inc.'s antisense compound GTI-2040, which began a Phase II trial in November, combined with docetaxel and prednisone in hormone-refractory prostate cancer.

Specifically, GTI-2040 binds to the messenger RNA that encodes the R2 component of ribonucleotide reductase. It's also being tested against colon cancer.

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