Enzyme therapy for hepatitis C being tested
By Beverly Creamer
Advertiser Staff Writer
Hawai'i patients suffering from hepatitis C stand to benefit from a new therapy on the horizon that appears to be more effective and have fewer side-effects than anything available now.
But the therapy is still in clinical trials, and final results of its effectiveness won't be known for more than a year.
The treatment involves daily injections — administered by the patients themselves — of naturally occurring enzymes called ribozymes, which attach to and cut other cells in half, destroying them. In this case ribozymes are used to destroy the hepatitis C virus.
"If we can get enough ribozyme into the liver, in principal we can cure that patient," said Ralph Christofferson, president of RPI (Ribozyme Pharmaceuticals Inc.) of Boulder, Colo., during a visit to Hawai'i for the recent BIO AsiaPacific 2001 conference that drew an international collection of biotechnology companies.
RPI has the patents to explore medical use of the 1992 Nobel-prize-winning discovery of ribozymes and their therapeutic potential.
"We don't know exactly how fast the virus is (in recreating itself), so we try to overload the system with ribozyme," said Christofferson, speaking of the way it fights hepatitis C. "It appears the more you give, the better."
But hepatitis C isn't the only disease that can potentially be controlled with ribozyme therapy. Hepatitis B and types of cancer are also being targeted in a series of studies that will eventually cost RPI several hundred thousand dollars, but could reap immense rewards.
There's been initial success in using ribozyme therapy against metastatic breast cancer, and clinical trials are moving ahead in that area as well. This type of ribozyme therapy, with a drug called Angiozyme, has been shown to cut off the blood supply to tumors, which stops their growth and spread.
"If we're successful," said Christofferson, "we have converted a death sentence to a disease that will be manageable, much the same way we manage diabetes or hypertension."
Although the drugs are all still in early clinical trials, they're showing such great promise that Christofferson was invited to speak at the BIO AsiaPacific conference.
"Ribozymes have the potential to become a new class of therapeutics," he said. "The number of times that's happened is pretty small. Antibiotics. When we learned how to clone proteins and make TPA (tissue plasminogen activator), the clot buster. The number of these new classes has been very small."
As is apparent with the hepatitis C and breast cancer treatments, ribozymes work differently against different diseases.
Heptazyme, the medication being tested against hepatitis C, for instance, binds to the virus and cuts it in half so it can't mutate and spread.
"Most sites mutate, but we've picked a site that is not expected to mutate. So the two independent pieces are not viable by themselves and the cell chews them up," he said.
The next round of clinical trials with Heptazyme begin in the fall at four Mainland sites. At this point, Hawai'i patients will not be included even though Hawai'i has one of the highest rates of hepatitis C infection in the country. Large-scale immigration from Asian countries, where hepatitis C infection is high, has been cited as one reason for Hawai'i's high rate.
The Centers for Disease Control and Prevention consider hepatitis C an epidemic in the United States, with about 4 million people infected. Worldwide, it's estimated as many as 125 million people are infected. Chronic infection can lead to liver inflammation, cirrhosis and cancer.
In fighting solid tumors, such as breast cancer, the ribozyme drug Angiozyme works somewhat differently, by preventing a receptor in the bloodstream called VEGF (vascular endothelial growth factor) from producing blood vessels that feed the tumor.
"If you could shut down the action of VEGF and prevent the tumors from getting a new blood supply, in principle you could prevent them from growing and spreading," said Christofferson.
VEGF is abundant during childhood, in healing wounds, and in pregnant women. But usually, healthy adults don't have it, he said.
"So when you see VEGF in a normal adult you know there's a problem. It's known to be causative for the growth of solid tumors."
In the first trial of Angiozyme, 30 patients — all with metastasized cancers and only a few months to live — gave themselves shots of the drug daily for 28 days. According to the terms of that study, patients would continue the drug as long as the tumor did not grow.
The results: in 61 percent of the patients, there was no growth in their tumors anywhere from one to 10 months. One patient has had no growth in her tumor in a year and she's still on the medicine.
"A huge metastasis hasn't grown. We think that's pretty interesting," said Christofferson.
"We're now designing five Phase Two studies in five specific tumors — breast cancer, colon cancer, small-cell lung cancer, melanoma and renal cancer — to see if we can prevent VEGF-dependent tumors from growing and metastasizing."
Christofferson expects definitive results in the next 12-24 months.
"If any one works," he said, "we'll have the brass ring."
