LONDON - Xenova Group plc disclosed positive results in the second of three Phase IIa trials of XR9576, a combination therapy for preventing cancer patients developing resistance to cytotoxic drugs.
David Oxlade, CEO of the Slough, UK, company, told BioWorld International the results of the third trial are due soon and XR9576 will be ready to enter Phase III before the end of 2000. "We are not going to pay for Phase III ourselves. We expect a partner to pick up the costs. We are talking to a number of [potential] partners and expect the trial to start in the first half of next year."
In this second trial, XR9576, a P-glycoprotein pump (P-gp) inhibitor, was administered with doxorubicin, one of the most frequently used cytotoxic drugs. There was no significant pharmacokinetic (PK) interaction between the two.
David Ferry, principal investigator at the Queen Elizabeth Medical Centre in Birmingham, said, "P-gp has been a difficult area to work in, with variable and sometimes significant interactions observed between many of the previously investigated P-gp inhibitors and the co-administered cytotoxics. XR9576's lack of variable and clinically significant PK interaction should provide an advantage in clinical practice, in that it should allow many different cytotoxic drugs to be used at, or close to, their normal doses."
The first trial showed no interaction with XR9576 and paclitaxel, the biggest selling cytotoxic. "These two are widely used cytoxics, and so we have demonstrated the potential for XR9576 to be used in a range of tumor types," Oxlade said. He also said the lack of interaction or side effects means that XR9576 could have potential in first-line therapy, to prevent drug resistance developing in the first place, rather than in treating resistance after patients relapse.
The third Phase IIa trial of XR9576 in combination with vinorelbine, being carried out at the National Cancer Institute in the U.S., is due to complete shortly.
It is estimated that between 30 percent and 80 percent of cancer patients develop resistance to cytotoxic drugs. Overproduction of the membrane protein P-gp, which pumps cytotoxics out of cancer cells, is the most common form of this resistance.
Oxlade said that investigators at the National Cancer Institute have administered the medical imaging agent sestamibi, with and without XR9576. In lesions that were expressing high levels of P-gp, sestamibi was pumped straight out of the cell. With XR9576, the dye accumulated in the cancer cells. "In other words, in the absence of XR9576, the tumor would not have seen any cytotoxic," he said.