By Mary Welch
AltaRex Corp. reached two milestones in the development of OvaRex MAb, its ovarian cancer treatment. The company received notice from a Data Safety Monitoring Board (DSMB) recommending the continuance of its potentially pivotal trial, and established a comparability plan with the FDA for switching to a cell culture manufacturing process.
"It's like working on a puzzle," said Richard Bagley, AltaRex's president and CEO. "We've put the edges together and now we're working on filling in the middle."
The Waltham, Mass., company now is conducting two Phase IIb trials as well as two open-label trials. The DSMB reviewed interim data from the largest trial involving at least 330 woman with advanced ovarian cancer who have completed surgery and chemotherapy.
"It is still a blinded study but the DSMB was looking to see if there were extraordinarily positive or extraordinarily negative results," said Chris Nicodemus, senior vice president of clinical research and development. "This is a vote of confidence that the board says we should continue."
The second issue, that of manufacturing the antibody, turned out to be one of the concerns that prompted AltaRex's former partner, Purdue Pharma LP, of Norwalk, Conn., to walk away from a potential $100 million collaboration late last year.
"It's an involved issue but Purdue was concerned about the comparability issue and whether we would have to repeat the clinical trials using the cell culture production," said Edward Fitzgerald, AltaRex's senior vice president and chief financial officer. "We have a clinical plan that, if approved by the FDA, will allow us to make manufacturing plans for the product without having to do new trials. It's an important milestone."
Purdue notified the company in October it would not exercise its option on the potential $100 million deal, causing AltaRex to cut its staff by 25 percent and reduce its burn rate by half. (See BioWorld Today, Oct. 25, 1999, p. 1.)
"Looking at it now, Purdue's decision was beneficial to us," Bagley said. "It allowed us to address some of the concerns they had on their minds, such as the manufacturing. And with some interim results coming out of the trials, particularly the open-label one in Vancouver, we're in a far better position to partner the drug in a deal that will be of real benefit to the company and our shareholders. We're moving forward boldly."
Last month, the company reported early results from its open-label Phase II trial in 13 patients with advanced-stage relapsed ovarian cancer, which is being conducted at the Vancouver Cancer Center in British Columbia. The median time to disease progression is eight to 12 weeks following second-line chemotherapy for ovarian cancer. In the Vancouver trial, results show that six OvaRex patients were progression-free for at least 12 weeks, while two were progression-free for more than 40 weeks. The expected median survival after second-line chemotherapy is about 40 weeks. To date, six patients have survived beyond 52 weeks with three additional patients still on the study.
"The variety of data we are getting is showing that there is activity and evidence of efficacy," Nicodemus said.
OvaRex is a modified monoclonal antibody-based immunotherapeutic associated with the ovarian cancer antigen, CA 125.
In addition to the Phase IIb trial with 330 women, a second Phase IIb trial is under way with a target of enrolling about 102 patients. The difference between the two trials is the scheduling of OvaRex treatment. In the larger trial, the women receive the antibody right after chemotherapy. In the second, OvaRex is not administered until the patients show elevated signs of a chemical marker, CA 125, indicating that the cancer may be preparing to return, Nicodemus said.
The company plans to file a biologics license application in late 2001, Fitzgerald said.
AltaRex's stock (TSE:AXO) closed Tuesday at C60 cents, up C11 cents.