Washington Editor

OSI Pharmaceuticals Inc. and partners Genentech Inc. and Roche Holdings Inc. filed the first sections of a rolling new drug application for the cancer candidate Tarceva, an endothelial growth factor receptor inhibitor.

The partners seek approval of Tarceva (erlotinib HCI) as a treatment for patients with incurable Stage IIIB/IV non-small-cell lung cancer who have failed standard therapy for advanced or metastatic disease. The FDA in September 2002 granted Tarceva fast-track status, which permits the companies to submit the NDA in sections.

OSI's stock (NASDAQ:OSIP) jumped $3.38 Wednesday, or 10.3 percent, to close at $36.20, while Genentech's (NYSE:DNA) moved up $2.09 to close at $94.40.

Kathy Galante, OSI's director of investor relations, told BioWorld Today the completed NDA should be filed in mid-2004 with FDA approval anticipated by the end of the year. The 730-patient registration study that would be the basis for the NDA remains blinded.

Colin Goddard, CEO of Melville, N.Y.-based OSI, told BioWorld Today he believes the worldwide, randomized registration trial might provide positive final results.

"Obviously, us moving ahead with the filing, I suppose, could be taken as a statement of confidence that we are going to hit the [primary] endpoint, but we currently don't have the data," he said.

Non-small-cell lung cancer (NSCLC) patients who would be candidates for Tarceva under its proposed indication historically have a median survival period of about 4.5 months. Therefore, the Phase III trial seeks to improve survival by 33 percent, to five months, six months or longer. "Obviously, we have hopes of doing better than that," Goddard said.

Secondary endpoints include time to symptomatic deterioration, progression-free survival and response rate.

The Phase III is evaluating a 150-mg, once-daily monotherapy dose of Tarceva vs. placebo. It is being conducted in collaboration with the National Cancer Institute of Canada's Clinical Trial group.

Tarceva is a small-molecule oral therapy designed to inhibit the tyrosine kinase activity of the HER1/EGFR signaling pathway inside the cell. OSI originally was developing Tarceva with Pfizer Inc., of New York. The Federal Trade Commission forced Pfizer to drop Tarceva in order to complete its acquisition of Warner-Lambert Co., of Morris Plains, N.J.

Subsequently, OSI snagged a deal valued at $187 million with Genentech, of South San Francisco, and Roche, of Basel, Switzerland, to take Tarceva forward. The partners share development costs. Genentech and OSI would share equally in profits if Tarceva were commercialized in the U.S., while Roche would retain foreign rights. Genentech and OSI would receive royalties for sales outside the U.S. (See BioWorld Today, Jan. 9, 2001.)

The partners in October released poor data from two front-line combination studies of the candidate in NSCLC. OSI was devalued only slightly on the news, mainly because Wall Street had anticipated negative results. Of the combination studies, Wednesday Galante told BioWorld Today, "We were disappointed, but not surprised."

That's because London-based AstraZeneca plc ran into similar problems with Iressa (gefitinib), an EGFR inhibitor approved in the U.S. for NSCLC. OSI lost 57.2 percent of its stock value (or $18.74) to close at $14.05 on a day in August 2002 when news became public that Iressa failed to improve survival in NSCLC when added to first-line standards of care. (See BioWorld Today, Aug. 21, 2002.)

Beyond NSCLC, Galante said Tarceva is being evaluated in other indications, including glioblastoma multiforme and bronchioloalveolar cell carcinoma.

Goddard said Tarceva has helped the company raise about $830 million since 2000.

"We've been successful in putting together a commercial organization with a couple of products in the market and others in the pipeline behind Tarceva, but there's no doubt that Tarceva is the flagship product, and it is what investors are focused on," he said. "In our view, it still can be a blockbuster, which would obviously set us on a course of really strong revenue growth."

OSI markets Novantrone (mitoxantrone concentrate for injection) for oncology indications and Gelclair for the relief of pain associated with oral mucositis.

The company has a pipeline of cancer candidates that include gene-targeted therapies focused in the areas of signal transduction and apoptosis and next-generation cytotoxic chemotherapy agents.