Harmless Virus Could Be an Answer to Cancer
It's called a reovirus (short for Respiratory Enteric Orphan virus), and it's a type which most people pick up by age 12 through inhalation or contact that causes few or no health problems. But when the virus enters cancer cells, it kills them.
Viruses, naturally, prefer cells that can't fight them off. And these cancer cells all have a common characteristic: They have a certain growth pathway, called the Ras pathway, turned on. "If a cell doesn't have that pathway turned on, nothing happens, so it's like an on-off switch for the virus's growth," Thompson explained. In the human body, very few normal cells have that Ras pathway turned on, and those die in the same amount of time the virus takes to kill them, so the body is not affected. "And that's where the story would end if only these few cells had the Ras pathway turned on all the time," Thompson added. "But it happens to be the state in most cancers."
"When the Ras pathway is turned on, it turns off the virus defense mechanism in the cell so the virus can go in and replicate itself," Thompson continued. It keeps replicating until its host -- the cancer cell -- is overwhelmed and dies, which happens within three days.
"Anywhere between two-thirds to 75% of the primary carcinomas -- ovarian, prostate, non-small cell lung cancer and so on -- actually have that pathway turned on," Thompson said. "In metastatic disease, which spreads beyond the primary tumor, it's between 95% to 100% that have the Ras pathway. So you have a disease that has this pathway, and a virus that for other reasons requires that pathway to grow."
Infecting the Cancer
That's where Oncolytics and its drug, Reolysin, come in play. Reolysin is "a variant of the virus we found in nature," explained Thompson. The treatment "is rather straightforward," he said. It involves five days of intravenous injections, and the side effects are few: Most commonly, patients run a small fever and feel a little tired.
Once the virus has killed the cancer cells, "the body actually clears the virus pretty effectively," Thompson explained, because the body mounts a normal immune response to the infection. "Normally, the latest we ever find the virus in the body is a couple of weeks after the first injection, and then it's completely gone," he says.
The company was founded in 1998 after several scientists at a virology lab in the University of Calgary started having problems growing the virus. As they screened it against established cells they found the correlation with the Ras pathway. "And then this little light bulb went on. Somebody said, wait a minute, that can be useful in oncology," Thompson tells.
Thompson lost his mother and an uncle to cancer, and himself got melanoma. "Right after that, while the surgery was still healing in my leg, I got a call from a colleague of mine in the Alberta government asking me whether I would talk to this group of researchers at the University of Calgary who were working on a virus. I had very heightened sensitivity to cancer at that time and had expertise in the area. So I got a close look at it, and that's how I got involved in it."
"That's how Oncolytics started," he added. "In less than a year, we went public, cross-listed and did six financings."
Phase 3 Clinical Trial
The company has completed about a dozen early-phase clinical trials so far, and has seven to eight ongoing for a broad range of cancers, including melanoma, lung and ovarian. But the real test will be the upcoming Phase 3 clinical trial for head and neck cancer.
The study is designed to combine Reolysin with the standard chemotherapy care for head and neck. In earlier studies, the response rate to the treatment was 42% when Reolysin was added to common therapy, much higher than the average 10% response rate for the disease.
If that response rate holds up, no doubt patients would be eager for the drug to reach the market. "We could be selling product by 2012, if everything lines up properly," said Thompson. "The sad part about head and neck patients is that you know very quickly whether your product works on them or not. The patients we're looking at have a median life expectancy of 4.5 months, so you don't have to wait much to know whether your product had benefit for the patients."
"The real question for us is what comes after that," Thompson added. "We're probably going to have to go after something that has a much larger market than head and neck and will also be a much larger clinical program than head and neck."
"Oncology is a very competitive, crowded space," Thompson acknowledged when asked about competitors. But he added that Oncolytics is looking at diseases that aren't getting much attention elsewhere.This also seems to be good news for patients with those diseases.
For now, Oncolytics has no bigger-company partners, which is rare for a biotech in advanced stages of clinical trials.ButBig Pharma has shown interest. "There are very few unpartnered Phase 3 oncology products. So we have certainly raised the interest of a number of our big pharma colleagues." But Oncolytics claims to be in no hurry and prefers to partner when it's best for the company and shareholders. Thompson indicates that a partnership could be announced by the end of the Phase 3 study.
Like all small biotechs, Oncolytics is facing challenges, most notably the possibility that its experimental drug will not work in late-stage trials despite positive early indications. But if anything, it's encouraging to see companies always in a quest to find improved treatments for a deadly disease.