OvaRex®
MAb is a monoclonal antibody – a biotech drug – designed to help the
patient’s immune system recognize and more effectively fight ovarian
cancer. OvaRex® MAb is given during the ‘watchful waiting’ period,
following successful front-line therapy. It may become recognized as
the most significant advance in ovarian cancer treatment since the use
of chemotherapy to treat this illness.
Comediennes such as Gilda Radner and Madeline Kahn, Oscar-winning
actresses like 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, who are stricken with
ovarian cancer. One in every 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 diagnosed. More than 16,000 women will die
because the symptoms are often subtle, and her doctor did not 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 by the final stage, into other
body organs such as the liver or lungs. Family doctors often fail to
properly diagnose “The Silent Killer” until it is 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 correctly diagnosed. A British survey discovered 75
percent of family doctors believed symptoms are only present during the
advanced stages of the cancer. By the time women are diagnosed for
ovarian cancer, 40 to 50 percent of the patients are in the advanced
stage, where there is little hope for survival.
Less than one-half the women diagnosed with ovarian cancer will live
five years. About 10 to 14 percent live beyond five years after their
diagnosis. Their choices have been limited, mainly reserved to
variations of chemotherapy drugs or a new way 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 safety profile of Eli Lilly’s Gemzar
for ovarian cancer patients, saying the 2.8 months increased survival
seen in studies of patients taking the drug wasn’t enough 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 treatments for ovarian cancer patients
include Cisplatin, with associated side effects such as nerve, kidney
and/or ear damage, Carboplatin (side effects: nerve damage in the arms
and/or legs, joint pain, and/or thrombocytopenia), Paclitaxel
(neurotoxicity), or Melphalan, with side effects which include
irreversible bone marrow failure, bone marrow suppression).
A woman stricken with ovarian cancer faces first surgery, then
chemotherapy. Recent widespread press heralding a new development in
treating ovarian cancer, intra-abdominal or intraperitoneal
chemotherapy, is just that: more 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. The results were first published in the
prestigious New England Journal of Medicine in December 2005. Most news
reports failed to mention that only 40 percent of the women treated
with the belly bath were able to complete all six cycles. Why? The
therapy relies upon infusions of Paclitaxel and Cisplatin (see side
effects in the previous paragraph). According to Dr. Robert Edwards,
research director of the Magee-Women’s Gynecologic Cancer in
Pittsburgh, “Many women don’t 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 treatments
“grueling.”
The unsolved problem of chemotherapy is 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 the therapy. Researchers are actively
pursuing new directions that may some day provide new hope for the
ovarian cancer patient. A University of Minnesota research study has
suggested the use of thalidomide, which would be used in conjunction
with chemotherapy, as a prospective means of increasing the likelihood
of remission. Minnesota cancer researcher Dr. Levi Downs explained, “It
prevents the tumor from making new blood vessels. Without new blood
vessels, the tumor can’t sufficiently feed new cells, so the cancer
can’t grow.” His randomized trial was small with only 65 patients (only
28 took thalidomide), and more testing will certainly be required.
New Hope for Ovarian Cancer Patients?
One promising technology that has 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 at about 64
research centers across the United States. 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 was 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 case of OvaRex® MAb, it is a
monoclonal antibody that binds specifically to the CA-125 antigen. Dr.
Tyrrell added, “The treatment doesn’t take long, and is given 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 trials are
ongoing. All of the patients have successfully completed their surgery
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 the recurrence rate is very high in the stage III / IV
late forms of ovarian cancer, with a time to relapse of about 10.4
months. Patients who have turned to OvaRex hope to delay that relapse.
Tyrrell noted, “In the original study, the average time to relapse was
delayed by about 14 months. If we can achieve that difference or better
in the current 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 different from other immunotherapeutic
treatments is, instead of attacking the body’s cancerous cells
directly, the monoclonal antibody targets the cancerous antigen in
circulation. Some believe it helps retrain the body’s immune system to
fight the ovarian cancer cells. The mechanism that reportedly has made
OvaRex® MAb effective 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 inflicted with a malignant tumor. The hypothesis behind the
tolerance issue is that the body fails to recognize the CA-125 antigen
as harmful. Introducing a foreign antibody, in this case the mouse
antibody against CA125, the body’s defense systems are awakened to the
ovarian cancer cells. This begins a chain reaction alerting the immune
system to battle 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.
As with many pioneering scientific breakthroughs, 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 roots. “It came out of the
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 using
antibodies to image the tumors so they could be evaluated in a cancer
patient’s body. “I worked with Dr. Mike Longenecker and we established
a company called Biomira (Toronto: BRA) in 1984,” Dr. Noujaim recalled.
“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 really a
glycopeptide,” explained Dr. Noujaim. “It’s a peptide that has a lot of
sugars on it present in the ascitis fluid from ovarian cancer
patients.” That is how Dr. Noujaim and his team developed the very
early antibody which is now used for OvaRex® MAb. “We sent some 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.’ I thought he was
joking with me.”
This is serendipity at work as Dr. Noujaim explained to us. “Richard
was imaging patients that were in the last stages of the disease,” he
pointed out. Monoclonal antibodies can be used as diagnostic agents in
oncology, when they are radiolabeled with a marker that can be imaged
by external detectors. “These patients had maybe four or five months to
live. All of a sudden, a year later and they’re still around.” Baum
urged Noujaim to investigate this further. Dr. Noujaim recalls him
saying, “Something is happening here. I’ve seen hundreds of patients,
but nothing like this.” From this encouragement, Noujaim began
formulating the potential mechanism of how this monoclonal antibody
would work. His sharp mind chased the puzzling questions raised by Dr.
Baum’s observations.
At this point of his recollections, Noujaim got excited, “Through sheer
serendipity, we were using murine antibodies, not humanized antibodies.
We were using foreign antibodies, a small amount of foreign
antibodies.” How in the world did Noujaim know to use murine (mouse)
antibodies? “Because that was the easiest way to do the imaging at the
time,” he replied. “Before you make a chimeric (something derived from
two different animal species) antibody, you start with a murine one. If
that one works, you humanize the antibody.” From this research, Noujaim
founded a company called AltaRex, which was taken public in 1995. “We
raised about $30 million and expanded the program.”
The serious effort 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’ve 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 believes it can apply to breast, ovarian, prostate and
pancreatic cancer. Indeed, 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.
“Our studies to date may show that vaccines may slow the growth of the
tumor with a very good safety profile,” concluded Dr. Noujaim. Then he
added something which bears investigating further, “There is the very
original (ovarian cancer) patient who was injected in 1987. She’s in
Germany, and according to Dr. Baum she was still alive a year ago.”
That’s nearly nine years later! “It’s a matter of great pride for me
that some people who received OvaRex® MAb are alive today,” he said.
While the company has licensed, under a royalty agreement, the OvaRex®
MAb technology to United Therapeutics, through that company’s
subsidiary, Unither Pharmaceuticals, ViRexx has retained rights to most
member nations of the European Union and certain other countries. Key
ones include France, the United Kingdom and the Benelux countries.
ViRexx has also established strategic relationships with Dompé
Farmaceutici, Medison Pharma, Ltd. and Genesis Pharma S.A. for certain
European and Middle-East Countries.
