Despite inconsistent results in Phase IIb trials, Canadian company AltaRex Corp. intends this year to file a rolling biologics license application for its late-stage ovarian cancer drug, OvaRex.
In a U.S. trial, OvaRex helped extend time before relapse in some women up to seven months. By contrast, in a similar Canadian trial, patients receiving the placebo actually experienced up to two months of extended time before relapse.
Richard Bagley, president and CEO of AltaRex in Waltham, Mass., told BioWorld Today that it’s not unusual to get very different results when trials are conducted in various countries. In the case of the Canadian study, Bagley said many of the patients clearly had traits that predispose them to quick relapse.
AltaRex’s stock (TSE:AXO) fell 66 percent Friday, or C$1.65, to close at C83 cents.
Bagley’s response to the drop: “If I could figure out stock markets, I wouldn’t be doing this for a living. I would be doing something else.”
He went on to say that AltaRex trades on a Canadian stock market and “over the last month, in anticipation of this announcement, there has been tremendous volatility in our stock. The purchase of stock in Canada can be quite different than in the U.S. First, there are far fewer institutional investors and most people who invest in our stock do a lot of trading day by day.”
OvaRex MAb (oregovomab), a fully foreign monoclonal antibody, has received FDA fast-track status for accelerated approval. Under the best of circumstances, AltaRex would complete the rolling BLA by the end of 2002 and win approval by mid-2003, Bagley said. (The rolling application allows a company to file in sections.)
“We have the confidence that we have a solid Phase II drug and we will move on and file this on the basis of these studies,” Bagley said. “That is what fast-track approval is all about.”
OvaRex targets an ovarian cancer-associated antigen, CA125, and is designed to induce immune responses against CA125 and to extend relapse-free or progression-free survival without effects on safety and quality of life.
The Phase IIb trial compared time to disease relapse (TTR) of OvaRex monotherapy to placebo following primary therapy, surgery and chemotherapy.
“The tragedy of ovarian cancer is obviously that treatment is not trivial, and 80 percent of women actually respond to it, but 20 percent don’t,” Bagley said. “The period of time between the end of chemotherapy and what is known as relapse which means you can find tumor again is called the watchful waiting period. During that watchful waiting period there is no drug treatment approved and that is where we studied our drug.”
The average watchful waiting period is 12 to 18 months before relapse, Bagley said. “During relapse disease, you are treated again with chemotherapy, which means for the women who have this tumor, the only time they have any quality of life is in the watchful waiting period, so what we want to be able to do is extend the period of time that they have quality of life. And that’s what we have established in the U.S. trial,” he said.
“The chemotherapy tends to knock out your immune system, so what we do with OvaRex is we boost immunity. When you boost your immune system, that is how you fight cancer.”
The 345-patient Phase IIb program consists of one Phase II trial conducted in the U.S. and one in Canada. In the U.S. trial, the median TTR for OvaRex was statistically significant (15.5 months vs. 8.5 months, p=.05). However, in the Canadian study, the result was not significant (8.2 months vs. 10.3 months for placebo).
“I really think in spite of the mixed results, the Canadian and U.S. results being different, I think this is an extraordinary occasion,” Bagley said. “We have moved the ball forward in ovarian cancer by doing trials the FDA asked us to do. We’ve produced some very solid Phase II results in the U.S.”
The company believes that these results, when combined with two other well-controlled U.S. trials and two open trials, will be sufficient for the BLA.
In total, Bagley said AltaRex will be filing data on more than 500 patients, including 200 in Germany who were treated with OvaRex and evaluated retrospectively.
“In a strange sort of way, this is kind of a historic moment,” Bagley said. “There have been no drugs approved in the watchful waiting period and more importantly, nobody has ever done a double-blind, placebo-controlled trial in this population. And our results show safety, efficacy and quality of life in the U.S. But it’s a tie in Canada.”
About two years ago, AltaRex was dropped by its partner, Norwalk, Conn.-based Purdue Pharma LP, in the development of both OvaRex and BrevaRex MAb, also a cancer treatment. (See BioWorld Today, Oct. 25, 1999.)
Bagley said AltaRex has a partner for southern Europe but is lacking partnerships in North America and northern Europe. “We have two choices. The advantage to having a partner is sharing expenses, but the disadvantage is that they take a large share of your profits,” he said. “We would like to get a partner where we retain a reasonable share of the profits, and that’s what we’ll attempt to do over the next couple of months.”
Ovarian cancer is referred to as the “disease that whispers” because vague symptoms and the difficult location of the ovaries lead to 75 percent of diagnoses being made late, when the disease has reached an advanced metastatic stage. While first-line treatment of surgery and chemotherapy usually results in temporary remission, recurrence of advanced-stage disease is almost inevitable and the five-year survival rate remains at less than 20 percent, a statement from the company said.