National Editor

Marching ahead with their global development plan for Tarceva (erlotinib), Genentech Inc. and OSI Pharmaceuticals Inc. said they have begun a Phase II trial with the drug against malignant glioma, or brain cancer.

"We literally enrolled our first patient this week," said Colleen Sweeney, senior manager of corporate relations for South San Francisco-based Genentech, adding that it's too early to estimate when the trial might finish. The companies might use positive Phase II data in a bid for approval, she said.

"The primary endpoint is overall response rate, and since there is such a medical need, we could take [positive data] to the FDA and talk about filing," Sweeney said.

Tarceva, which inhibits the tyrosine kinase activity of the HER1/epithelial growth factor signaling pathway, is already the subject of a Phase III program testing its power against non-small-cell lung cancer.

That program consists of three studies. Two of them - one conducted by Genentech and the other by Roche Holdings Inc., of Basel, Switzerland (a third partner in Tarceva's development) - are assessing the drug as a first-line agent in combination with approved chemotherapy regimens.

"We should get those results back later this year," Sweeney said.

Another is being conducted by OSI in collaboration with the National Cancer Institute Canada Clinical Trials Group, evaluating Tarceva as a single agent in a second-line/third-line setting.

"That's tracking for the very end of this year or early next year," she told BioWorld Today, adding that all the NSCLC trials "have survival endpoints. A certain number of deaths need to occur before we can do the analysis."

London-based AstraZeneca plc's EGFR drug Iressa (gefitinib) failed in Phase III against NSCLC a year ago, with consequences for others developing similar therapies, but a 10 percent response rate for Iressa in a Phase II study led to its approval earlier this year. (See BioWorld Today, Aug. 20, 2002, and May 6, 2003.)

Tarceva also is being tested in combination with gemcitabine in a Phase III trial with previously untreated, advanced pancreatic cancer patients.

"The trial's fully enrolled but we don't expect data until next year," Sweeney said.

Friday, though, the spotlight was on brain cancer. Having gained orphan drug status for Tarceva against glioma, Genentech - in collaboration with a nonprofit group of neuro-oncology centers called the Accelerate Brain Cancer Cure Clinical Network - plans to enroll up to 110 patients who have experienced their first relapse of the disease, which is the most common form of primary brain cancer and strikes about 7,000 people annually in the U.S.

"If you look at EGFR overexpression, it's much higher in brain cancer than in any of the other areas," Sweeney said, suggesting that EGFR may play a "special role" in this disease so that Tarceva could be particularly effective.

Genentech and OSI disclosed results from the Phase I trial in glioma during the rain of favorable cancer news from this year's meeting of the American Society of Clinical Oncology in Chicago. (See BioWorld Today, June 3, 2003.)

Physicians now attack glioma with surgery, radiation and chemotherapy.

"Some tumors are operable and some aren't," Sweeney noted. "A lot of times the chemotherapy has to be administered via wafers that are implanted," since available drugs - unlike the small-molecule Tarceva - can't cross the blood-brain barrier.

"It's definitely a difficult disease for physicians to treat," she said, noting that patients have a life expectancy after diagnosis of 12 months to 18 months.

Aiming to stoke its pipeline further back, Genentech had more news less than a week ago, when it bought for an undisclosed amount patent rights for diagnostics and small-molecule products based on a gene from Human Genome Sciences Inc., of Rockville, Md.

"We're looking at what disease states are appropriate targets," Sweeney said.

Genentech's stock (NYSE:DNA) closed Friday at $75.39, down 41 cents. Melville, N.Y.-based OSI's shares (NASDAQ:OSIP) ended the day at $29.85, down 6 cents.