Adventrx Pharmaceuticals Inc. and the FDA have agreed on a special protocol assessment for a Phase III trial of its chemotherapy enhancing drug, CoFactor, expected to start this quarter.
At the same time, the San Diego-based firm withdrew plans for a public offering, citing adverse market conditions. Adventrx filed a prospectus earlier this month, planning to sell 15.5 million shares. The share price had not yet been determined, but based on the May 12 closing price of $4.84, the company had estimated net proceeds of $69 million for general corporate purposes, including clinical and preclinical development.
"The market has taken a downturn on recent negative news, in general," said Andrea Lynn, director of marketing at Adventrx, "and we just felt it wasn't the right time."
She added that the decision is not expected to affect the upcoming CoFactor pivotal trial, and she could not estimate costs for the study.
The company, which posted a net loss of $21 million, or 31 cents per share, for the first quarter, had $22 million in cash as of March 30. Shares of Adventrx (AMEX:ANX) closed at $4.29 Monday, up 9 cents.
Under the SPA, the company intends to evaluate CoFactor, a folate-based biomodulator drug aimed at reducing the toxicity and enhancing the activity of cancer agent 5-fluorouracil (5-FU). An expected 1,200 patients with metastatic colorectal cancer will be treated with 5-FU plus Avastin (bevacizumab, from South San Francisco-based Genentech Inc.) and randomized into two groups to receive CoFactor or leucovorin, the only FDA-approved biomodulator of 5-FU.
Progression-free survival is the primary endpoint. Secondary endpoints include response rate, overall survival and incidence and severity of adverse events.
The company has not provided a time frame for the trial. It "really depends on patient recruitment," Lynn told BioWorld Today, adding that Adventrx anticipates setting up 50 U.S. clinical sites.
A follow-up period is planned for the conclusion of treatment.
Designed to enhance 5-FU's ability to inhibit cancer growth, CoFactor is the active metabolite of the generically available leucovorin, but, unlike leucovorin, does not need to undergo a chemical conversion to deliver the active form of folate.
Adventrx reported Phase II results in January showing that 85 percent of patients receiving CoFactor and 5-FU as first-line treatment in metastatic colorectal cancer had their tumors shrink or stabilize. Data also indicated a longer-than-expected time to tumor progression, with no grade 3 or 4 drug-related gastrointestinal or hematological toxicities.
A Phase IIb trial of CoFactor in metastatic colorectal cancer is ongoing in Europe and India.
Co-Factor also is being developed for use with 5-FU against breast cancer, and the product has been studied in gastric and pancreatic cancers. The company is hoping that the product will demonstrate significant benefit and patient survival and will become a replacement for leucovorin. In 2005, worldwide sales of leucovorin exceeded $300 million.
Adventrx so far has developed CoFactor on its own, though the company is in "ongoing discussions with potential partners," Lynn said.
Behind Co-Factor, the company's development pipeline consists of other cancer products, including ANX-530, an emulsion formulation of vinorelbine tartrate. It's designed to reduce vein irritation caused by vinorelbine, an approved chemotherapy agent in non-small-cell lung, breast and ovarian cancers. Adventrx expects to file an investigational new drug application to begin a bioequivalence study of ANX-530 in the third quarter. ANX-530 comes from Carlsbad, Calif.-based SD Pharmaceuticals Inc. The companies had a licensing agreement formed in the fall, but Adventrx bought the firm outright last month, issuing 2.1 million shares in a stock swap.
In the area of infectious disease, the company plans to submit an investigational new drug application later this year to begin clinical testing of Thiovir, a reverse transcriptase inhibitor, in HIV/AIDS. Thiovir also demonstrated in preclinical studies potential antiviral activity against avian flu.