West Coast Editor

Adventrx Pharmaceuticals Inc.'s positive data from the marketing-enabling trial with its vein-saving emulsion equivalent for Navelbine (vinorelbine), the vinca alkaloid against non-small-cell lung cancer, sends the company to the FDA for discussions next month.

A new drug application could come as early as the first half of 2008, said analyst Brian Lian, with CIBC World Markets, who predicted that progress with the compound - called ANX-530 - will drive the stock near term, along with possible partnership news.

Stephen Dunn, analyst with Dawson James in Boca Raton, Fla., told BioWorld Today that although the ANX-530's potential is "financially not huge, they acquired a whole bunch of product candidates from SD Pharmaceuticals Inc. that are all based on this [nano-emulsion technology]," and the success with vinorelbine helps validate the April 2006 merger.

Shares of Adventrx (AMEX:ANX) closed Friday at 64 cents, down a penny.

In taking over SD, of Carlsbad, Calif., San Diego-based Adventrx gained worldwide intellectual property rights, excluding rights for China, Taiwan, Hong Kong and Macau, to a portfolio of eight oncology and infectious disease therapeutic product candidates, including ANX-530 which had been the subject of an earlier license agreement between the firms.

Full results from the crossover comparison, 31-patient trial, which was designed to prove a pharmacokinetics match with London-based GlaxoSmithKline plc's Navelbine, should be available in the first quarter of next year, and will be submitted for disclosure in an upcoming medical conference. Approved for use in NSCLC alone or with cisplatin, Navelbine and its generic versions sold about $200 million in 2006.

The equivalence in the Adventrx trial was determined by comparing areas under the curve (AUC, or how much drug is circulating in the body over time) and maximum plasma concentrations (Cmax, or top concentration of drug in the blood at a specific time). If the upper and lower bounds of the AUC ratio's and the Cmax ratio's 90 percent confidence interval ranged from 0.80 to 1.25, then ANX-530 and Navelbine were considered equivalent.

In the first week, patients got either ANX-530 or Navelbine. After a "washout" period, they were dosed with the opposite drug during the second week. The FDA has said a single successful study of that type could support a Section 505(b)(2) NDA.

Vinorelbine, which also has shown activity in breast, ovarian and other cancers, works by disrupting microtubule formulation. By delivering the drug as an emulsion, ANX-530 cuts down on vein irritation from intravenous delivery.

The below-dollar stock price is a far cry from Adventrx's 52-week high of $2.98, shares having tumbled 79 percent last month, closing at $2.02, on news that a comparison of the firm's CoFactor (also known as ANX-510) to leucovorin missed its primary endpoint of reducing serious hematological or gastrointestinal adverse events associated with the chemotherapy drug 5-fluorouracil. (See BioWorld Today, Oct. 2, 2007.)

CoFactor is the active metabolite of leucovorin and is intended to boost the efficacy and decrease the toxicity of 5-FU by allowing more stable binding to the drug's target enzyme. Adventrx still has a Phase II trial with 5-FU in breast cancer, but a Phase III trial with 5-FU and Avastin (bevacizumab, Genentech Inc.) in metastatic colorectal cancer was discontinued earlier this month. The stop came after advice from the trial's data safety monitoring board, which cited a slow accrual rate and the fact that analysis of Phase IIb data showed no significant differences between the treatment arm and control arm with regard to either safety or efficacy.

The CoFactor breast cancer trial will complete enrollment this year and produce data in the second half of 2008. CIBC analysts are not optimistic, but Dunn is keeping the faith. "I personally don't think CoFactor is dead yet," he said, pointing to differences in administration between trials (bolus in the U.S., infusion in the European Union) that could explain outcomes.

"You're not going to have a problem if you're using infusion, but with a bolus, you overload the leucovorin. That's where you get the benefit of using CoFactor," Dunn said.

Along with ANX-530 and CoFactor, Adventrx has ANX-514, an emulsion of the chemotherapy drug Taxotere (docetaxel, Sanofi-Aventis Group), slated late this year to begin a bioequivalence study that also aims at approval through the 505(b)(2) pathway.

Dunn also sees promise in ANX-201 (Thiovir), a preclinical reverse transcriptase inhibitor for HIV. The pyrophosphate analogue delivers thiophosphonoformate and phosphonoformate (foscarnet) in capsule form.

"Foscarnet works very well in HIV patients, but it's intravenous, so they have to go to the hospital," Dunn said. In March, Adventrx signed a deal with Pharmatek Laboratories Inc., of San Diego, for the manufacture of ANX-201, and Phase I/II combination trials in HIV patients are expected to begin in the third quarter.

Adventrx reported a third-quarter loss per share of 7 cents, in line with analyst estimates, and finished the period with about $39 million in cash and cash equivalents. CIBC estimated a cash burn in the fourth quarter between $4 million and $6 million, for a full-year net loss of about $22 million.