By Mary Welch
Cell Therapeutics Inc. said Friday it obtained the licensing rights to a water soluble form of Bristol-Myers Squibb Co.'s well-known cancer drug, Taxol (paclitaxel), a move that has the Seattle-based company smiling after Thursday's disclosure that Johnson & Johnson was backing away from their collaboration on lisofylline.
The decision by Johnson & Johnson, of New Brunswick, N.J., followed release four months ago of negative Phase III trial results of lisofylline, Cell Therapeutics' lead product, for bone marrow transplants. (See BioWorld Today, July 17, 1998, p. 1.)
"Taxol was introduced in 1992 for ovarian cancer and in 1994 for breast cancer, and it is a $1 billion drug," Cell Therapeutics President and CEO James Bianco said. "We have a water soluble form of that drug that is infused (into the patient) within minutes. You can double the dose (from a standard Taxol dosage) with no adverse side effects and it has shown partial or complete tumor regression. What is missing from this picture? We kept thinking it would be pulled away from us."
Cell Therapeutics licensed the product, PG-TXL (polyglutamic acid paclitaxel), from the University of Texas M.D. Anderson Cancer Center, in Houston.
"One of the researchers there, Sidney Wallace, had a sister with breast cancer who almost died from the side effects of Taxol. People get very, very sick from the side effects and the infusion delivery system. He wanted a way to deliver Taxol without the side effects," Bianco said.
"We were looking for an addition to our oncology pipeline. We looked at over 500 opportunities before we found this one — and it was in the diagnostic radiation department — hardly where you'd expect to find a discovery like this. We couldn't believe it."
Soluble Form Patentable, Says Bianco
In the water soluble form of Taxol, a polymer of polyglutamic acid binds to the native paclitaxel, which is derived from the bark and needles of an evergreen tree, the Pacific yew.
What makes PG-TXL different — legally different — from Taxol is that the amino acid polymer binds to the paclitaxel and doesn't come apart. "It's a new chemical entity that is independently patentable," Bianco stated.
M.D. Anderson has applied for a patent of PG-TXL and in negotiating its license, Cell Therapeutics was concerned New York-based Bristol-Myers might interfere.
Taxol is approved for breast and ovarian cancer patients who have failed previous therapies. Although highly successful, Taxol has produced allergic side reactions in patients, and even death.
For example, patients with advanced ovarian cancer have a 6 to 7 percent response rate at current dosage levels of Taxol. When the dosage is doubled, there is a 65 percent response rate, but at that dosage, patients experience life-threatening side effects. (See BioWorld Today, Sept. 9, 1994, p. 1.)
Paclitaxel is an oily compound that doesn't mix with water. So it is combined with a 50-50 measure of castor oil and alcohol for infusion into the patient.
"It's like a salad dressing," said Bianco. "Try putting that into your veins. Your blood pressure drops, you have to take antihistamines and steroids. They almost have to put you under because people pass out from the infusion side effects. And it takes anywhere from three to six hours to get a Taxol treatment."
PG-TXL is mixed with sugar water and, within minutes, the drug is administered intravenously. "The patients just walk out," he added. "Just think of the economics of this the delivery method."
Not only does Cell Therapeutics insist its drug's level of side effects will be much less than Taxol's, but when administered in higher doses, complete tumor regressions were observed in both ovarian and breast cancer models. In preclinical animal testing, PG-TXL was given at twice the maximum dosage of paclitaxel and was found to be safe.
"There was a complete regression of the tumors. That's called a cure. And it was safe. We're taking a proven effective cancer product and making major improvements in effectiveness and safety," Bianco said.
Cell Therapeutics paid an up-front licensing fee to the M.D. Anderson cancer center and will pay milestones or royalties as well. "Not a large fee," Bianco said.
The company expects to enter Phase I/II trials either by the end of this year or early 1999. An FDA filing for a new drug application would follow, with PG-TXL potentially on the market by 2002 or 2003.
"That would be an attractive timetable," Bianco allowed.
Cell Therapeutics and M.D. Anderson Cancer Center are also looking at verifying if PG-TXL can be used in other cancer indications beside breast and ovarian cancer. Early testing indicates that it may have applications in lung and colon cancers.
Cell Therapeutics stock (NASDAQ:CTIC) closed Friday at $3.031, up $0.531. *