By Karen Pihl-Carey
In an effort to carry the ovarian cancer drug OvaRex MAb through clinical development on its own, AltaRex Corp. filed in Canada to raise funds through U.S. investors in a public offering. The company also announced its intention to begin in the second quarter an additional pivotal study of OvaRex in order to secure the data needed for regulatory filings in the U.S. and Europe.
The plan, said AltaRex President and CEO Richard Bagley, is to fund pivotal OvaRex trials through next year, and then to partner the product as it nears a biologics license application (BLA) filing at the end of 2001.
"I would like to have the opportunity to get significant rights when we commercialize," Bagley told BioWorld Today. "We're doing the financing so we can take OvaRex further on our own, because we've already invested about 80 percent of what it's going to take to get this product registered in America."
Purdue Pharma LP, of Norwalk, Conn., initially showed interest in partnering with AltaRex on OvaRex MAb and BrevaRex MAb, another anticancer drug, in a $100 million deal last year. Purdue, however, chose not to exercise its option to exclusive worldwide development and commercialization rights due to concerns about the comparability of two different manufacturing processes. The company worried that AltaRex's move from a manufacturing process in mice to a manufacturing process in cell cultures might require repetitive clinical trials of OvaRex. Purdue's decision led to AltaRex laying off a quarter of its staff in order to reduce its burn rate by 50 percent. (See BioWorld Today, May 14, 1999, p. 1; Oct. 18, 1999, p. 1; and Oct. 25, 1999.)
Bagley said he could give few details about the public offering. The company filed a preliminary prospectus with the Ontario Securities Commission in Canada. HSBC Securities Inc., of Toronto, will act as lead agent in the offering. Roth Capital Partners Inc., of Los Angeles, and Greenwich Global LP, of Greenwich, Conn., will act as placement agents in the U.S. The offering will be priced in the context of the market. Bagley would not say how much the company intends to raise, only that it intends to raise the funds through U.S. investors. It is an offering intended to help position AltaRex to better access capital and provide trading markets outside of Canada, he said.
AltaRex, a Canadian-registered company with headquarters in Waltham, Mass., has completed enrollment in both its pivotal double-blind, placebo-controlled lead OvaRex trial with 345 patients and its supporting trial with 55 patients. Primary endpoint analysis of both trials will be conducted in the second and third quarters of next year.
The trials are different in that women receive the antibody right after chemotherapy in the larger trial. OvaRex is not administered to patients in the second trial until they show elevated signs of a chemical marker, CA 125, indicating the cancer may be preparing to return.
AltaRex expects commercialization in the U.S. in 2002 and in Europe in 2003. Bagley estimates the drug could generate anywhere from $500 million to $1 billion in sales. "If we generate [that], we get the payback for having taken most of the risk and having done most of the work."
In order to get to that point, however, the company had to address the manufacturing comparability concern brought up by Purdue Pharma.
Lonza Biologics, of Basel, Switzerland, will manufacture the new material for the additional open-label controlled study of OvaRex MAb, which will involve about 150 patients. Those patients will first be treated with the available manufactured product until the new material is available in early 2001. AltaRex decided to conduct the additional study for three reasons: the FDA wanted safety data with the new material; European regulations require additional data for switching of a manufacturing process; and the company thought it beneficial to have new data on the human anti-mouse antibody (HAMA) response. The HAMA response occurs when a patient's immune system destroys the monoclonal antibodies and their effectiveness as long-term treatments.
"When you make an antibody in mice, you run the risk of viral contamination," Bagley said. "So a better way to go is to take your clones and put them into fermenters, and the clones produce your antibody for you. This is known as a cell culture manufacturing technique."
The cell culture technique provides an economic advantage to the company and a safety advantage to the patients, and likely would be the required manufacturing process by European authorities, he said.
Data from the new trial would be pooled with placebo data from another trial in order to give a "richer package" to regulatory authorities. The new trial does not delay the BLA filing.
"This trial will be better for the patients because there's no placebo arm in it, and it will be quicker for us because we don't have to enroll twice the number of patients," Bagley said.
Both OvaRex MAb and BrevaRex MAb are based on AltaRex's Anti-idiotype Induction Therapy approach, which the company believes enhances the immune system's ability to produce its own antitumor response. BrevaRex is in Phase I trials for people showing elevated MUC1 levels.
AltaRex's stock (TSE:AXO) closed Thursday at $1.09, down 2 cents.