Fighting Over Ovarian Cancer by Stimulating the Body Defenses

Comediennes like Gilda Radner and Madeline Kahn, Oscar-winning actresses such as Loretta Young and Sandy Dennis, singers Laura Nyro and Dinah Shore, actor Pierce Brosnan’s wife Cassandra Harris, actress Jessica Tandy, former Connecticut governor Ella Grasso, and Martin Luther King’s wife Coretta Scott King all died of ovarian cancer. It’s not just celebrities, politicians or movie stars, that are stricken with ovarian cancer. One in each 55 U.S. women is at risk for ovarian cancer. The American Cancer Society estimates about 22,000 new cases of ovarian cancer will be identified. More than 16,000 women will die because the symptoms are often subtle, and her doctor didn’t recognize the symptoms soon enough. It is the leading cause of death from gynecologic malignancies, and the fifth leading cause of cancer deaths among women.

Silent and undetected, this cancer often spreads beyond the Ovary or ovaries into the abdominal cavity, or from the final stage, into other body organs like the lungs or liver. Family doctors often fail to correctly diagnose “The Silent Killer” until it’s too late. Last August, University of California Davis researchers reported 40 percent of women told their doctors about their symptoms for as long as a year before they were properly diagnosed. A British survey found 75 percent of family doctors believed symptoms are only present during the advanced stages of the cancer. By the time girls are diagnosed for ovarian cancer, 40 to 50 percent of their patients are in the advanced stage, where there is little hope for success.

The women diagnosed with ovarian cancer that will live five years are less than one-half. Their choices are limited, mainly reserved to variations of chemotherapy drugs or a new method to delivery the drug. The general public is often unaware of the side effects ovarian cancer patients suffer during chemotherapy. In mid March, the U.S. Food and Drug Administration criticized the security profile of Eli Lilly’s Gemzar for ovarian cancer patients, saying the 2.8 months increased survival found in studies of patients taking the drug was not sufficient to offset the treatment’s increased toxicity which included anemia, neutropenia (a blood disorder) and thrombocytopenia (reduced platelets in the blood). Presently used first-line therapies for ovarian cancer patients include Cisplatin, with related side effects such as nerve, kidney and/or ear injury, Carboplatin (side effects: nerve damage in the arms and/or legs, joint pain, and/or thrombocytopenia), Paclitaxel (neurotoxicity), or Melphalan, with side effects including irreversible bone marrow failure, bone marrow suppression).

A girl stricken with ovarian cancer faces first surgery, then chemotherapy. The “belly bath,” as it has been nicknamed by some television reporters, it has been highly praised because the treatment can extend life by about 16 months more than “regular” chemotherapy. Most news reports failed to mention that only 40 percent of those women treated with the belly bath could finish all six cycles. Why? The therapy relies upon infusions of Paclitaxel and Cisplatin (see side effects in the prior paragraph). According to Dr. Robert Edwards, research director of the Magee-Women’s Gynecologic Cancer at Pittsburgh, “Many women do not feel well enough to work for the duration of the intra-abdominal (therapy).” Some patients, such as Cindy Pakalnis of Marshall (Pennsylvania) have called the therapies “grueling.”

The unsolved problem of chemotherapy is that the reduction in the “quality of life.” While some life extension has been proven, the patient’s life deteriorates. Many patients struggle with balancing the loss in quality of life with the rigors of this treatment. A University of Minnesota research study has indicated the use of thalidomide, which might be used along with chemotherapy, as a potential way of increasing the likelihood of remission. Without new blood vessels, the tumor can’t sufficiently feed fresh cells, so the cancer can’t grow.” His randomized trial was small with only 65 patients (just 28 took thalidomide), and more testing will surely be required.

One promising technology that’s been developed over the past decade is OvaRex® MAb. It was developed by ViRexx Medical Corp., an Edmonton-based company, which trades on the American Stock Exchange (ticker symbol: REX) and on the Toronto Stock Exchange (ticker symbol: VIR). Now licensed to Unither Pharmaceuticals, a wholly owned subsidiary of United Therapeutics (NASDAQ: UTHR), OvaRex® MAb is currently undergoing two identical Phase III trials in about 64 research centers across america. One trial has completed enrollment, according to a mid December news release issued by ViRexx Medical Corp.

We spoke with ViRexx Medical Corp’s Chief Executive Officer, Dr. Tyrrell who had been the Dean of the Faculty of Medicine and Dentistry at the University of Alberta and the Director of the Glaxo Heritage Research Institute. “OvaRex® MAb is our lead candidate for the treatment of ovarian cancer, and is an intravenous infusion of a monoclonal antibody,” he said. Monoclonal antibodies are a new breed of biotech drugs that are extremely specific; that is, each antibody binds to only one particular antigen. In the event of OvaRex® MAb, it is a monoclonal antibody that binds specifically to the CA-125 antigen. Dr. Tyrrell added, “The therapy doesn’t take long, and is awarded every 4 weeks for the first 3 injections, and then once every 3 months until the patient relapses”.

Dr. Tyrrell talked about the current Phase III studies, “The All of the patients have successfully completed their operation and front-line chemotherapy and are now in what we call the ‘watchful waiting’ period. It is in this phase that we treat the patients with OvaRex® MAb with the hopes of increasing the time to disease relapse.” He explained that the recurrence rate is quite high in the stage III / IV late types of ovarian cancer, with a time to relapse of about 10.4 months. Patients that have turned to OvaRex hope to delay that relapse. Tyrrell noted, “In the first study, the average time to relapse was delayed by about 14 months. If we could achieve that difference or better in the present Phase III trials, it would be a major advance for the treatment of ovarian cancer” He expects an analysis of the current OvaRex® MAb studies to be completed by the second or third quarter of 2007.

What makes OvaRex® MAb distinct from other Immunotherapeutic treatments is, instead of attacking the body’s cancerous cells directly, the monoclonal antibody targets the cancerous antigen in circulation. Some think it helps retrain the body’s immune system to fight the ovarian cancer cells. The mechanism that reportedly has made OvaRex® MAb successful is how it alerts the body to recognize and fight the CA-125.

ViRexx has addressed the “tolerance problem” a body suffers when it has become inundated with a malignant tumor. The theory behind the tolerance issue is that the body fails to recognize the CA-125 antigen as harmful. This starts a chain reaction alerting the immune system to combat the invading antibody CA125 complex. The body’s defense systems are reprogrammed to attack the CA-125 antigen and seek to destroy it. Along with that destruction comes the attempt of the immune response to eliminate the cancerous cells from the body.

Serendipity is what lies behind the OvaRex® MAb story. As one technology was being developed, another — the murine monoclonal antibody treatment for ovarian cancer — came about by accident. We talked to its inventor, Dr. Antoine Noujaim, about the biotech drug’s origins. “It came from this imaging technology,” the Professor Emeritus of the University of Alberta explained. In the early 1980s, biotech companies, such as Immunomedics and Cytomedics were researching tumors and utilizing antibodies to image the tumors so that they can be evaluated in a cancer patient’s body. “I worked with Dr. Mike Longenecker and we established a company named Biomira (Toronto: BRA) in 1984,” Dr. Noujaim remembered. “We had a number of targets and then needed to make specific antibodies.” Part of his effort was to target certain cancers, such as prostate, breast and ovarian cancer.

“We developed antibodies against a mucin, which is truly a glycopeptide,” explained Dr. Noujaim. “It’s a peptide which has a great deal of sugars on it present in the ascitis fluid from ovarian cancer patients.” That is how Dr. Noujaim and his team developed the very ancient antibody which is currently used for OvaRex® MAb. “We sent a number of these antibodies to Professor Richard Baum in Germany for imaging of ovarian cancer patients,” Noujaim remembered. “Dr. Baum phoned back, after some time, and told me, ‘The patients I was imaging here had advanced ovarian cancer and some of them seem to have done quite well after we gave them a couple of shots (of the B43.13 antibody, the clinical name for OvaRex® MAb) to image the tumor’

That is serendipity at work as Dr. Noujaim explained to us. “Richard was imaging patients that were in the last phases of the disease,” he pointed out. Monoclonal antibodies can be used as diagnostic agents in oncology, when they’re radiolabeled with a marker which could be imaged by external sensors. “These patients had maybe four or five months to live. All of a sudden, a year later and they are still around.” Baum urged Noujaim to investigate that further. I have seen hundreds of patients, but nothing like this.” From this encouragement, Noujaim began formulating the possible mechanism of how this monoclonal antibody would work.

At this stage of his recollections, Noujaim got excited, “Through sheer serendipity, we were using murine antibodies, not humanized antibodies. We were using foreign antibodies, a small number of foreign antibodies.” “Since that was the easiest way to do the imaging at the moment,” he answered. “Before you make a chimeric (something derived from two different animal species) antibody, you begin with a murine one. If that one works, you humanize the antibody.” From this study, Noujaim founded a company named AltaRex, which was taken public in 1995. “We raised about $30 million and expanded the program.”

The serious attempt to develop the antibodies began in 1996. Having conducted trials in Canada and Europe, it was a “massive undertaking” Noujaim told us. “We had over 500 patients injected with the murine monoclonal antibody.” He extrapolated beyond OvaRex® MAb, saying, “We have proven completely The mechanism of action on this, how it works. It is so unique it may apply to All of the other antibodies we have.” Noujaim thinks it can apply to breast, ovarian, prostate and pancreatic cancer. Truly, BrevaRex® MAb for breast Cancer and multiple myeloma patients has completed Phase 1 trials, and ProstaRex® MAb for prostate cancer patients is at the pre-clinical stage.arian Cancer by Stimulating the Body’s Defenses

“Our studies to date may show that vaccines may impede the Development of the tumor with an excellent safety profile,” concluded Dr. Noujaim. Then he added something that bears investigating further, “There is the exact original (ovarian cancer) individual who had been injected in 1987. She’s in Germany, and according to Dr. Baum she was still alive a year ago” That is nearly nine decades later! “It’s a topic of fantastic pride to me that some individuals who received OvaRex® MAb are living now,” he explained.

While the company has licensed, under a royalty arrangement, That the OvaRex® MAb technologies to United Therapeutics, through that corporation’s Subsidiary, Unither Pharmaceuticals, ViRexx has kept rights to most member Nations of the European Union and certain other countries. Key ones include France, the United Kingdom and the Benelux nations. ViRexx has also established strategic relationships with Dompé Farmaceutici, Medison Pharma, Ltd. and Genesis Pharma S.A. for particular European and Middle-East Countries.