Exelixis Inc. said Wednesday it began a Phase III trial in bile duct cancer with the only product in its growing pipeline that is in-licensed: XL119.
The trial is expected to enroll at 60 centers in the U.S., Canada and Europe about 600 patients with inoperable bile duct tumors. The two-arm study will have a primary endpoint of survival and will compare XL119 to a 5-FU/leucovorin regimen. Against such a lethal cancer, secondary endpoints offer little, said Exelixis' president and CEO, George Scangos.
"Survival is the only reliable benefit for these patients," he said. "I don't think most oncologists view progression [based on] tumor size as reliable."
With the survival endpoint, there is no set timeline for completion of the trial, but previous data and the history of the cancer itself give some guidance as to when data might be available.
"These are really aggressive tumors, and in historical controls, survival time is maybe five months," Scangos told BioWorld Today. "The Phase II data suggested a survival time of about nine months."
XL119 was in-licensed from Bristol-Myers Squibb Co., of New York, which got it from the National Cancer Institute in Bethesda, Md. The compound is semi-synthetic and a topoisomerase II inhibitor, although Scangos said that is "almost certainly not its sole mechanism of action."
What the others might be is not clear, but XL119 has performed in the clinic. Phase II data from 33 patients with bile duct tumors provided encouraging results regarding overall and progression-free survival. Similar results were seen in 36 non-small-cell lung cancer patients enrolled in a Phase II trial. Those data were presented at last year's American Society of Clinical Oncology meeting. At this year's meeting in New Orleans, the company presented promising Phase II data in refractory breast cancer patients. But while it appears to have potential in several areas, Scangos said there aren't plans for a second Phase III trial.
"Not immediately," he said. "The National Cancer Institute will continue to do a series of Phase II studies in other cancers and we'll assess that data." Right now, the company is focused on the bile duct Phase III study, he said.
Bile duct cancer strikes about 10,000 U.S. patients annually, and about 30,000 globally, so those gauging potential market size for XL119 "can work from there," Scangos said. The product has orphan drug status in the U.S., and South San Francisco-based Exelixis is considering applying for that designation in Europe.
Although XL119 came from BMS, Exelixis owns the product free and clear. Partnering is an option, and the company is in discussions with potential suitors now, but Scangos allowed that "one of our goals is to bring compounds to the market in the U.S.," noting that that prospect is "more difficult in Asia and Europe."
The company had cash, cash equivalents, short-term investments and restricted cash totaling $207 million as of March 31. It lost $28.8 million in the first quarter, under generally accepted accounting principles. Scangos said Exelixis is "not in any urgent need" of finances, but he pointed to a growing list of future clinical trials and noted that "those all cost money."
Underneath XL119 in Exelixis' pipeline is XL784, an inhibitor of the ADAM-10 metalloprotease enzyme, which has completed Phase I work. Another cancer product, XL647, which targets multiple receptor tyrosine kinases, has entered Phase I in patients with solid tumors. Exelixis also has the preclinical compounds XL999, XL844, XL820 and XL880. An investigational new drug application filing for XL999 is expected soon and could be followed by filings for the other three in the first half of 2005, Scangos said.
"Since we already know a lot about those compounds, I think the attrition rate would be low," he said. "But we have another group that is potentially the subject of INDs later on next year."
The company has notable collaborative partners in BMS and GlaxoSmithKline plc, of London, in deals separately valued at potentially hundreds of millions of dollars. The work with GSK includes vascular biology, inflammatory disease and cancer. With BMS, Exelixis has had "a long-standing collaboration" in oncology. While those deals provide funding and the potential reward of milestone payments, they also keep the drug discovery wheels turning. (See BioWorld Today, July 19, 2001, and Oct. 30, 2002.)
"It looks to me that we're going to have five or more products in the clinic by early next year or the first half of next year," Scangos said. "And all but one of those will have come out of our own R&D engine."
The company's stock (NASDAQ:EXEL) rose 66 cents Wednesday to close at $9.35.